PCOS is a common problem, with a prevalence of 6% to 10% among women of reproductive age.¹ Patients with PCOS often present with hirsutism, acne, female androgenetic alopecia, oligomenorrhea (also known as infrequent menstrual bleeding), amenorrhea, infertility, overweight, or obesity. In addition, many patients with PCOS have insulin resistance, dyslipidemia, metabolic syndrome, and an increased risk for developing type 2 diabetes mellitus (DM).² A simplified approach to the diagnosis of PCOS will save health care resources by reducing the use of low-value diagnostic tests. A simplified approach to the treatment of PCOS will support patient medication adherence and improve health outcomes.

Simplify the diagnosis of PCOS

Simplify PCOS diagnosis by focusing on the core criteria of hyperandrogenism and oligo-ovulation. There are 3 major approaches to diagnosis:

1. the 1990 National Institutes of Health (NIH) criteria³
2. the 2003 Rotterdam criteria^4,5
3. the 2008 Androgen Excess and PCOS Society (AES) criteria.⁶

Using the 1990 NIH approach, the diagnosis of PCOS is made by the presence of 2 core criteria: hyperandrogenism and oligo-ovulation, typically manifested as oligomenorrhea. In addition, other causes of hyperandrogenism should be excluded, including nonclassical adrenal hyperplasia (NCAH) due to 21-hydroxylase deficiency.³ Using the 1990 NIH criteria, PCOS can be diagnosed based on history (oligomenorrhea) and physical examination (assessment of the severity of hirsutism), but laboratory tests including total testosterone are often ordered.⁷

The Rotterdam approach to the diagnosis added a third criteria, the detection by ultrasonography of a multifollicular ovary and/or increased ovarian volume.^4,5 Using the Rotterdam approach, PCOS is diagnosed in the presence of any 2 of the following 3 criteria: hyperandrogenism, oligo-ovulation, or ultrasound imaging showing the presence of a multifollicular ovary, identified by ≥ 12 antral follicles (2 to 9 mm in diameter) in each ovary or increased ovarian volume (> 10 mL).^4,5

The Rotterdam approach using ovarian ultrasound as a criterion to diagnose PCOS is rife with serious problems, including:

• The number of small antral follicles in the normal ovary is age dependent, and many ovulatory and nonhirsute patients have ≥ 12 small antral follicles in each ovary.^8,9
• There is no consensus on the number of small antral follicles needed to diagnose a multifollicular ovary, with recommendations to use thresholds of 12^4,5 or 20 follicles¹⁰ as the diagnostic cut-off.
• Accurate counting of the number of small ovarian follicles requires transvaginal ultrasound, which is not appropriate for many young adolescent patients.
• The process of counting ovarian follicles is operator-dependent.
• The high cost of ultrasound assessment of ovarian follicles (≥ $500 per examination).

The Rotterdam approach supports the diagnosis of PCOS in a patient with oligo-ovulation plus an ultrasound showing a multifollicular ovary in the absence of any clinical or laboratory evidence of hyperandrogenism.^3,4,5 This approach to the diagnosis of PCOS is rejected by both the 1990 NIH³ and AES⁶ recommendations, which require the presence of hyperandrogenism as the sine qua non in the diagnosis of PCOS. I recommend against diagnosing PCOS in a non-hyperandrogenic patient with oligo-ovulation and a multifollicular ovary because other diagnoses are also possible, such as functional hypothalamic oligo-ovulation, especially in young patients. The Rotterdam approach also supports the diagnosis of PCOS in a patient with hyperandrogenism, an ultrasound showing a multifollicular ovary, and normal ovulation and menses.^3,4 For most patients with normal, regular ovulation and menses, the testosterone concentration is normal and the only evidence of hyperandrogenism is hirsutism. Patients with normal, regular ovulation and menses plus hirsutism usually have idiopathic hirsutism. Idiopathic hirsutism is a problem caused by excessive 5-alpha-reductase activity in the hair pilosebaceous unit, which catalyzes the conversion of weak androgens into dihydrotestosterone, a potent intracellular androgen that stimulates terminal hair growth.¹¹ In my opinion, the Rotterdam approach to diagnosing PCOS has created unnecessary confusion and complexity for both clinicians and patients. I believe we should simplify the diagnosis of PCOS and return to the 1990 NIH criteria.³

On occasion, a patient presents for a consultation and has already had an ovarian ultrasound to assess for a multifollicular ovary. I carefully read the report and, if a multifollicular ovary has been identified, I consider it as a secondary supporting finding of PCOS in my clinical assessment. But I do not base my diagnosis on the ultrasound finding. Patients often present with other laboratory tests that are secondary supporting findings of PCOS, which I carefully consider but do not use to make a diagnosis of PCOS. Secondary supporting laboratory findings consistent with PCOS include: 1) a markedly elevated anti-müllerian hormone (AMH) level,¹² 2) an elevated fasting insulin level,^2,13 and 3) an elevated luteinizing hormone (LH) to follicle-stimulating hormone (FSH) ratio.^13,14 But it is not necessary to measure AMH, fasting insulin, LH, and FSH levels. To conserve health care resources, I recommend against measuring those analytes to diagnose PCOS.

Continue to: Simplify the core laboratory tests...

Simplify the core laboratory tests

Simplify the testing used to support the diagnosis of PCOS by measuring total testosterone, sex-hormone binding globulin (SHBG) and early morning 17-hydroxyprogesterone (17-OH Prog).

The core criteria for diagnosis of PCOS are hyperandrogenism and oligo-ovulation, typically manifested as oligomenorrhea or amenorrhea. Hyperandrogenism can be clinically diagnosed by assessing for the presence of hirsutism.⁷ Elevated levels of total testosterone, free testosterone, androstenedione, and/or dehydroepiandrosterone sulfate (DHEAS) suggest the presence of hyperandrogenism. In clinical practice, the laboratory approach to the diagnosis of hyperandrogenism can be simplified to the measurement of total testosterone, SHBG, and 17-OH Prog. By measuring total testosterone and SHBG, an estimate of free testosterone can be made. If the total testosterone is elevated, it is highly likely that the free testosterone is elevated. If the SHBG is abnormally low and the total testosterone level is in the upper limit of the normal range, the free testosterone is likely to be elevated.¹⁵ Using this approach, either an elevated total testosterone or an abnormally low SHBG indicate elevated free testosterone. For patients with hyperandrogenism and oligo-ovulation, an early morning (8 to 9 AM) 17-OH Prog level ≤ 2 ng/mL rules out the presence of NCAH due to a 21-hydroxylase deficiency.¹⁶ In my practice, the core laboratory tests I order when considering the diagnosis of PCOS are a total testosterone, SHBG, and 17-OH Prog.

Additional laboratory tests may be warranted to assess the patient diagnosed with PCOS. For example, if the patient has amenorrhea due to anovulation, tests for prolactin, FSH, and thyroid-stimulating hormone levels are warranted to assess for the presence of a prolactinoma, primary ovarian insufficiency, or thyroid disease, respectively. If the patient has a body mass index (BMI) ≥ 25 kg/m², a hemoglobin A1c concentration is warranted to assess for the presence of prediabetes or DM.² Many patients with PCOS have dyslipidemia, manifested through low high-density lipoprotein cholesterol levels and elevated low-density lipoprotein cholesterol levels, and a lipid panel assessment may be indicated. Among patients with PCOS, the most common lipid abnormality is a low high-density lipoprotein cholesterol level.¹⁷

Simplify the treatment of PCOS

Simplify treatment by counseling about lifestyle changes and prescribing an estrogen-progestin contraceptive, spironolactone, and metformin.

Most patients with PCOS have dysfunction in reproductive, metabolic, and dermatologic systems. For patients who are overweight or obese, lifestyle changes, including diet and exercise, that result in a 5% to 10% decrease in weight can improve metabolic balance, reduce circulating androgens, and increase menstrual frequency.¹⁸ For patients with PCOS and weight issues, referral to nutrition counseling or a full-service weight loss program can be very beneficial. In addition to lifestyle changes, patients with PCOS benefit from treatment with estrogen-progestin medications, spironolactone, and metformin.

Combination estrogen-progestin medications will lower LH secretion, decrease ovarian androgen production, increase SHBG production, decrease free testosterone levels and, if given cyclically, cause regular withdrawal bleeding.¹⁹ Spironolactone is an antiandrogen, which blocks the intracellular action of dihydrotestosterone and improves hirsutism and acne. Spironolactone also modestly decreases circulating levels of testosterone and DHEAS.²⁰ For patients with metabolic problems, including insulin resistance and obesity, weight loss and/or treatment with metformin can help improve metabolic balance, which may result in restoration of ovulatory menses.^21,22 Metformin can be effective in restoring ovulatory menses in both obese and lean patients with PCOS.²² The most common dermatologic problem caused by PCOS are hirsutism and acne. Both combination estrogen-progestin medications and spironolactone are effective treatments for hirsutism and acne.²³

Estrogen-progestin hormones, spironolactone, and metformin are low-cost medications for the treatment of PCOS. Additional high-cost options for treatment of PCOS in obese patients include bariatric surgery and glucagon-like peptide (GLP-1) agonist medications (liraglutide and exenatide). For patients with PCOS and a body mass index (BMI) ≥ 35 kg/m², bariatric surgery often results in sufficient weight loss to resolve the patient’s hyperandrogenism and oligo-ovulation, restoring spontaneous ovulatory cycles.²⁴ In a study of more than 1,000 patients with: PCOS; mean BMI, 44 kg/m²; mean age, 31 years who were followed post-bariatric surgery for 5 years, > 90% of patients reported reductions in hirsutism and resumption of regular menses.²⁵ For patients with PCOS seeking fertility, bariatric surgery often results in spontaneous pregnancy and live birth.²⁶ GLP-1 agonists, including liraglutide or exenatide with or without metformin are effective in reducing weight, decreasing androgen levels, and restoring ovulatory menses.^27,28

In my practice, I often prescribe 2 or 3 core medications for a patient with PCOS: 1) combination estrogen-progestin used cyclically or continuously, 2) spironolactone, and 3) metformin.¹⁹ Any estrogen-progestin contraceptive will suppress LH and ovarian androgen production; however, in the treatment of patients with PCOS, I prefer to use an estrogen-progestin combination that does not contain the androgenic progestin levonorgestrel.²⁹ For the treatment of PCOS, I prefer to use an estrogen-progestin contraceptive with a non-androgenic progestin such as drospirenone, desogestrel, or gestodene. I routinely prescribe spironolactone at a dose of 100 mg, once daily, a dose near the top of the dose-response curve. A daily dose ≤ 50 mg of spironolactone is subtherapeutic for the treatment of hirsutism. A daily dose of 200 mg of spironolactone may cause bothersome breakthrough bleeding. When prescribing metformin, I usually recommend the extended-release formulation, at a dose of 750 mg with dinner. If well tolerated, I will increase the dose to 1,500 mg with dinner. Most of my patients with PCOS are taking a combination of 2 medications, either an estrogen-progestin contraceptive plus spironolactone or an estrogen-progestin contraceptive plus metformin.¹⁹ Some of my patients are taking all 3 medications. All 3 medications are very low cost.

For patients with PCOS and anovulatory infertility, letrozole treatment often results in ovulatory cycles and pregnancy with live birth. In obese PCOS patients, compared with clomiphene, letrozole results in superior live birth rates.³⁰ Unlike clomiphene, letrozole is not approved by the US Food and Drug Administration for the treatment of anovulatory infertility.

The diagnosis of PCOS is often delayed due to confusion about how to make the diagnosis.³¹ To simplify the diagnosis of PCOS and improve patient encounters for PCOS, I focus on 2 core criteria: hyperandrogenism and oligo-ovulation. I recommend against ordering ultrasound imaging to assess for the presence of a multifollicular ovary. To simplify the treatment of PCOS I frequently prescribe an estrogen-progestin contraceptive, spironolactone, and metformin. By simplifying the diagnosis and treatment of PCOS, ObGyns will reduce patient confusion, improve outcomes, and save health care resources. ●

PCOS is a common problem, with a prevalence of 6% to 10% among women of reproductive age.¹ Patients with PCOS often present with hirsutism, acne, female androgenetic alopecia, oligomenorrhea (also known as infrequent menstrual bleeding), amenorrhea, infertility, overweight, or obesity. In addition, many patients with PCOS have insulin resistance, dyslipidemia, metabolic syndrome, and an increased risk for developing type 2 diabetes mellitus (DM).² A simplified approach to the diagnosis of PCOS will save health care resources by reducing the use of low-value diagnostic tests. A simplified approach to the treatment of PCOS will support patient medication adherence and improve health outcomes.

Simplify the diagnosis of PCOS

Simplify PCOS diagnosis by focusing on the core criteria of hyperandrogenism and oligo-ovulation. There are 3 major approaches to diagnosis:

1. the 1990 National Institutes of Health (NIH) criteria³
2. the 2003 Rotterdam criteria^4,5
3. the 2008 Androgen Excess and PCOS Society (AES) criteria.⁶

Using the 1990 NIH approach, the diagnosis of PCOS is made by the presence of 2 core criteria: hyperandrogenism and oligo-ovulation, typically manifested as oligomenorrhea. In addition, other causes of hyperandrogenism should be excluded, including nonclassical adrenal hyperplasia (NCAH) due to 21-hydroxylase deficiency.³ Using the 1990 NIH criteria, PCOS can be diagnosed based on history (oligomenorrhea) and physical examination (assessment of the severity of hirsutism), but laboratory tests including total testosterone are often ordered.⁷

The Rotterdam approach to the diagnosis added a third criteria, the detection by ultrasonography of a multifollicular ovary and/or increased ovarian volume.^4,5 Using the Rotterdam approach, PCOS is diagnosed in the presence of any 2 of the following 3 criteria: hyperandrogenism, oligo-ovulation, or ultrasound imaging showing the presence of a multifollicular ovary, identified by ≥ 12 antral follicles (2 to 9 mm in diameter) in each ovary or increased ovarian volume (> 10 mL).^4,5

The Rotterdam approach using ovarian ultrasound as a criterion to diagnose PCOS is rife with serious problems, including:

• The number of small antral follicles in the normal ovary is age dependent, and many ovulatory and nonhirsute patients have ≥ 12 small antral follicles in each ovary.^8,9
• There is no consensus on the number of small antral follicles needed to diagnose a multifollicular ovary, with recommendations to use thresholds of 12^4,5 or 20 follicles¹⁰ as the diagnostic cut-off.
• Accurate counting of the number of small ovarian follicles requires transvaginal ultrasound, which is not appropriate for many young adolescent patients.
• The process of counting ovarian follicles is operator-dependent.
• The high cost of ultrasound assessment of ovarian follicles (≥ $500 per examination).

The Rotterdam approach supports the diagnosis of PCOS in a patient with oligo-ovulation plus an ultrasound showing a multifollicular ovary in the absence of any clinical or laboratory evidence of hyperandrogenism.^3,4,5 This approach to the diagnosis of PCOS is rejected by both the 1990 NIH³ and AES⁶ recommendations, which require the presence of hyperandrogenism as the sine qua non in the diagnosis of PCOS. I recommend against diagnosing PCOS in a non-hyperandrogenic patient with oligo-ovulation and a multifollicular ovary because other diagnoses are also possible, such as functional hypothalamic oligo-ovulation, especially in young patients. The Rotterdam approach also supports the diagnosis of PCOS in a patient with hyperandrogenism, an ultrasound showing a multifollicular ovary, and normal ovulation and menses.^3,4 For most patients with normal, regular ovulation and menses, the testosterone concentration is normal and the only evidence of hyperandrogenism is hirsutism. Patients with normal, regular ovulation and menses plus hirsutism usually have idiopathic hirsutism. Idiopathic hirsutism is a problem caused by excessive 5-alpha-reductase activity in the hair pilosebaceous unit, which catalyzes the conversion of weak androgens into dihydrotestosterone, a potent intracellular androgen that stimulates terminal hair growth.¹¹ In my opinion, the Rotterdam approach to diagnosing PCOS has created unnecessary confusion and complexity for both clinicians and patients. I believe we should simplify the diagnosis of PCOS and return to the 1990 NIH criteria.³

On occasion, a patient presents for a consultation and has already had an ovarian ultrasound to assess for a multifollicular ovary. I carefully read the report and, if a multifollicular ovary has been identified, I consider it as a secondary supporting finding of PCOS in my clinical assessment. But I do not base my diagnosis on the ultrasound finding. Patients often present with other laboratory tests that are secondary supporting findings of PCOS, which I carefully consider but do not use to make a diagnosis of PCOS. Secondary supporting laboratory findings consistent with PCOS include: 1) a markedly elevated anti-müllerian hormone (AMH) level,¹² 2) an elevated fasting insulin level,^2,13 and 3) an elevated luteinizing hormone (LH) to follicle-stimulating hormone (FSH) ratio.^13,14 But it is not necessary to measure AMH, fasting insulin, LH, and FSH levels. To conserve health care resources, I recommend against measuring those analytes to diagnose PCOS.

Continue to: Simplify the core laboratory tests...

Simplify the core laboratory tests

Simplify the testing used to support the diagnosis of PCOS by measuring total testosterone, sex-hormone binding globulin (SHBG) and early morning 17-hydroxyprogesterone (17-OH Prog).

The core criteria for diagnosis of PCOS are hyperandrogenism and oligo-ovulation, typically manifested as oligomenorrhea or amenorrhea. Hyperandrogenism can be clinically diagnosed by assessing for the presence of hirsutism.⁷ Elevated levels of total testosterone, free testosterone, androstenedione, and/or dehydroepiandrosterone sulfate (DHEAS) suggest the presence of hyperandrogenism. In clinical practice, the laboratory approach to the diagnosis of hyperandrogenism can be simplified to the measurement of total testosterone, SHBG, and 17-OH Prog. By measuring total testosterone and SHBG, an estimate of free testosterone can be made. If the total testosterone is elevated, it is highly likely that the free testosterone is elevated. If the SHBG is abnormally low and the total testosterone level is in the upper limit of the normal range, the free testosterone is likely to be elevated.¹⁵ Using this approach, either an elevated total testosterone or an abnormally low SHBG indicate elevated free testosterone. For patients with hyperandrogenism and oligo-ovulation, an early morning (8 to 9 AM) 17-OH Prog level ≤ 2 ng/mL rules out the presence of NCAH due to a 21-hydroxylase deficiency.¹⁶ In my practice, the core laboratory tests I order when considering the diagnosis of PCOS are a total testosterone, SHBG, and 17-OH Prog.

Additional laboratory tests may be warranted to assess the patient diagnosed with PCOS. For example, if the patient has amenorrhea due to anovulation, tests for prolactin, FSH, and thyroid-stimulating hormone levels are warranted to assess for the presence of a prolactinoma, primary ovarian insufficiency, or thyroid disease, respectively. If the patient has a body mass index (BMI) ≥ 25 kg/m², a hemoglobin A1c concentration is warranted to assess for the presence of prediabetes or DM.² Many patients with PCOS have dyslipidemia, manifested through low high-density lipoprotein cholesterol levels and elevated low-density lipoprotein cholesterol levels, and a lipid panel assessment may be indicated. Among patients with PCOS, the most common lipid abnormality is a low high-density lipoprotein cholesterol level.¹⁷

Simplify the treatment of PCOS

Simplify treatment by counseling about lifestyle changes and prescribing an estrogen-progestin contraceptive, spironolactone, and metformin.

Most patients with PCOS have dysfunction in reproductive, metabolic, and dermatologic systems. For patients who are overweight or obese, lifestyle changes, including diet and exercise, that result in a 5% to 10% decrease in weight can improve metabolic balance, reduce circulating androgens, and increase menstrual frequency.¹⁸ For patients with PCOS and weight issues, referral to nutrition counseling or a full-service weight loss program can be very beneficial. In addition to lifestyle changes, patients with PCOS benefit from treatment with estrogen-progestin medications, spironolactone, and metformin.

Combination estrogen-progestin medications will lower LH secretion, decrease ovarian androgen production, increase SHBG production, decrease free testosterone levels and, if given cyclically, cause regular withdrawal bleeding.¹⁹ Spironolactone is an antiandrogen, which blocks the intracellular action of dihydrotestosterone and improves hirsutism and acne. Spironolactone also modestly decreases circulating levels of testosterone and DHEAS.²⁰ For patients with metabolic problems, including insulin resistance and obesity, weight loss and/or treatment with metformin can help improve metabolic balance, which may result in restoration of ovulatory menses.^21,22 Metformin can be effective in restoring ovulatory menses in both obese and lean patients with PCOS.²² The most common dermatologic problem caused by PCOS are hirsutism and acne. Both combination estrogen-progestin medications and spironolactone are effective treatments for hirsutism and acne.²³

Estrogen-progestin hormones, spironolactone, and metformin are low-cost medications for the treatment of PCOS. Additional high-cost options for treatment of PCOS in obese patients include bariatric surgery and glucagon-like peptide (GLP-1) agonist medications (liraglutide and exenatide). For patients with PCOS and a body mass index (BMI) ≥ 35 kg/m², bariatric surgery often results in sufficient weight loss to resolve the patient’s hyperandrogenism and oligo-ovulation, restoring spontaneous ovulatory cycles.²⁴ In a study of more than 1,000 patients with: PCOS; mean BMI, 44 kg/m²; mean age, 31 years who were followed post-bariatric surgery for 5 years, > 90% of patients reported reductions in hirsutism and resumption of regular menses.²⁵ For patients with PCOS seeking fertility, bariatric surgery often results in spontaneous pregnancy and live birth.²⁶ GLP-1 agonists, including liraglutide or exenatide with or without metformin are effective in reducing weight, decreasing androgen levels, and restoring ovulatory menses.^27,28

In my practice, I often prescribe 2 or 3 core medications for a patient with PCOS: 1) combination estrogen-progestin used cyclically or continuously, 2) spironolactone, and 3) metformin.¹⁹ Any estrogen-progestin contraceptive will suppress LH and ovarian androgen production; however, in the treatment of patients with PCOS, I prefer to use an estrogen-progestin combination that does not contain the androgenic progestin levonorgestrel.²⁹ For the treatment of PCOS, I prefer to use an estrogen-progestin contraceptive with a non-androgenic progestin such as drospirenone, desogestrel, or gestodene. I routinely prescribe spironolactone at a dose of 100 mg, once daily, a dose near the top of the dose-response curve. A daily dose ≤ 50 mg of spironolactone is subtherapeutic for the treatment of hirsutism. A daily dose of 200 mg of spironolactone may cause bothersome breakthrough bleeding. When prescribing metformin, I usually recommend the extended-release formulation, at a dose of 750 mg with dinner. If well tolerated, I will increase the dose to 1,500 mg with dinner. Most of my patients with PCOS are taking a combination of 2 medications, either an estrogen-progestin contraceptive plus spironolactone or an estrogen-progestin contraceptive plus metformin.¹⁹ Some of my patients are taking all 3 medications. All 3 medications are very low cost.

For patients with PCOS and anovulatory infertility, letrozole treatment often results in ovulatory cycles and pregnancy with live birth. In obese PCOS patients, compared with clomiphene, letrozole results in superior live birth rates.³⁰ Unlike clomiphene, letrozole is not approved by the US Food and Drug Administration for the treatment of anovulatory infertility.

The diagnosis of PCOS is often delayed due to confusion about how to make the diagnosis.³¹ To simplify the diagnosis of PCOS and improve patient encounters for PCOS, I focus on 2 core criteria: hyperandrogenism and oligo-ovulation. I recommend against ordering ultrasound imaging to assess for the presence of a multifollicular ovary. To simplify the treatment of PCOS I frequently prescribe an estrogen-progestin contraceptive, spironolactone, and metformin. By simplifying the diagnosis and treatment of PCOS, ObGyns will reduce patient confusion, improve outcomes, and save health care resources. ●

PCOS is a common problem, with a prevalence of 6% to 10% among women of reproductive age.¹ Patients with PCOS often present with hirsutism, acne, female androgenetic alopecia, oligomenorrhea (also known as infrequent menstrual bleeding), amenorrhea, infertility, overweight, or obesity. In addition, many patients with PCOS have insulin resistance, dyslipidemia, metabolic syndrome, and an increased risk for developing type 2 diabetes mellitus (DM).² A simplified approach to the diagnosis of PCOS will save health care resources by reducing the use of low-value diagnostic tests. A simplified approach to the treatment of PCOS will support patient medication adherence and improve health outcomes.

Simplify the diagnosis of PCOS

Simplify PCOS diagnosis by focusing on the core criteria of hyperandrogenism and oligo-ovulation. There are 3 major approaches to diagnosis:

1. the 1990 National Institutes of Health (NIH) criteria³
2. the 2003 Rotterdam criteria^4,5
3. the 2008 Androgen Excess and PCOS Society (AES) criteria.⁶

Using the 1990 NIH approach, the diagnosis of PCOS is made by the presence of 2 core criteria: hyperandrogenism and oligo-ovulation, typically manifested as oligomenorrhea. In addition, other causes of hyperandrogenism should be excluded, including nonclassical adrenal hyperplasia (NCAH) due to 21-hydroxylase deficiency.³ Using the 1990 NIH criteria, PCOS can be diagnosed based on history (oligomenorrhea) and physical examination (assessment of the severity of hirsutism), but laboratory tests including total testosterone are often ordered.⁷

The Rotterdam approach to the diagnosis added a third criteria, the detection by ultrasonography of a multifollicular ovary and/or increased ovarian volume.^4,5 Using the Rotterdam approach, PCOS is diagnosed in the presence of any 2 of the following 3 criteria: hyperandrogenism, oligo-ovulation, or ultrasound imaging showing the presence of a multifollicular ovary, identified by ≥ 12 antral follicles (2 to 9 mm in diameter) in each ovary or increased ovarian volume (> 10 mL).^4,5

The Rotterdam approach using ovarian ultrasound as a criterion to diagnose PCOS is rife with serious problems, including:

• The number of small antral follicles in the normal ovary is age dependent, and many ovulatory and nonhirsute patients have ≥ 12 small antral follicles in each ovary.^8,9
• There is no consensus on the number of small antral follicles needed to diagnose a multifollicular ovary, with recommendations to use thresholds of 12^4,5 or 20 follicles¹⁰ as the diagnostic cut-off.
• Accurate counting of the number of small ovarian follicles requires transvaginal ultrasound, which is not appropriate for many young adolescent patients.
• The process of counting ovarian follicles is operator-dependent.
• The high cost of ultrasound assessment of ovarian follicles (≥ $500 per examination).

The Rotterdam approach supports the diagnosis of PCOS in a patient with oligo-ovulation plus an ultrasound showing a multifollicular ovary in the absence of any clinical or laboratory evidence of hyperandrogenism.^3,4,5 This approach to the diagnosis of PCOS is rejected by both the 1990 NIH³ and AES⁶ recommendations, which require the presence of hyperandrogenism as the sine qua non in the diagnosis of PCOS. I recommend against diagnosing PCOS in a non-hyperandrogenic patient with oligo-ovulation and a multifollicular ovary because other diagnoses are also possible, such as functional hypothalamic oligo-ovulation, especially in young patients. The Rotterdam approach also supports the diagnosis of PCOS in a patient with hyperandrogenism, an ultrasound showing a multifollicular ovary, and normal ovulation and menses.^3,4 For most patients with normal, regular ovulation and menses, the testosterone concentration is normal and the only evidence of hyperandrogenism is hirsutism. Patients with normal, regular ovulation and menses plus hirsutism usually have idiopathic hirsutism. Idiopathic hirsutism is a problem caused by excessive 5-alpha-reductase activity in the hair pilosebaceous unit, which catalyzes the conversion of weak androgens into dihydrotestosterone, a potent intracellular androgen that stimulates terminal hair growth.¹¹ In my opinion, the Rotterdam approach to diagnosing PCOS has created unnecessary confusion and complexity for both clinicians and patients. I believe we should simplify the diagnosis of PCOS and return to the 1990 NIH criteria.³

On occasion, a patient presents for a consultation and has already had an ovarian ultrasound to assess for a multifollicular ovary. I carefully read the report and, if a multifollicular ovary has been identified, I consider it as a secondary supporting finding of PCOS in my clinical assessment. But I do not base my diagnosis on the ultrasound finding. Patients often present with other laboratory tests that are secondary supporting findings of PCOS, which I carefully consider but do not use to make a diagnosis of PCOS. Secondary supporting laboratory findings consistent with PCOS include: 1) a markedly elevated anti-müllerian hormone (AMH) level,¹² 2) an elevated fasting insulin level,^2,13 and 3) an elevated luteinizing hormone (LH) to follicle-stimulating hormone (FSH) ratio.^13,14 But it is not necessary to measure AMH, fasting insulin, LH, and FSH levels. To conserve health care resources, I recommend against measuring those analytes to diagnose PCOS.

Continue to: Simplify the core laboratory tests...

Simplify the core laboratory tests

Simplify the testing used to support the diagnosis of PCOS by measuring total testosterone, sex-hormone binding globulin (SHBG) and early morning 17-hydroxyprogesterone (17-OH Prog).

The core criteria for diagnosis of PCOS are hyperandrogenism and oligo-ovulation, typically manifested as oligomenorrhea or amenorrhea. Hyperandrogenism can be clinically diagnosed by assessing for the presence of hirsutism.⁷ Elevated levels of total testosterone, free testosterone, androstenedione, and/or dehydroepiandrosterone sulfate (DHEAS) suggest the presence of hyperandrogenism. In clinical practice, the laboratory approach to the diagnosis of hyperandrogenism can be simplified to the measurement of total testosterone, SHBG, and 17-OH Prog. By measuring total testosterone and SHBG, an estimate of free testosterone can be made. If the total testosterone is elevated, it is highly likely that the free testosterone is elevated. If the SHBG is abnormally low and the total testosterone level is in the upper limit of the normal range, the free testosterone is likely to be elevated.¹⁵ Using this approach, either an elevated total testosterone or an abnormally low SHBG indicate elevated free testosterone. For patients with hyperandrogenism and oligo-ovulation, an early morning (8 to 9 AM) 17-OH Prog level ≤ 2 ng/mL rules out the presence of NCAH due to a 21-hydroxylase deficiency.¹⁶ In my practice, the core laboratory tests I order when considering the diagnosis of PCOS are a total testosterone, SHBG, and 17-OH Prog.

Additional laboratory tests may be warranted to assess the patient diagnosed with PCOS. For example, if the patient has amenorrhea due to anovulation, tests for prolactin, FSH, and thyroid-stimulating hormone levels are warranted to assess for the presence of a prolactinoma, primary ovarian insufficiency, or thyroid disease, respectively. If the patient has a body mass index (BMI) ≥ 25 kg/m², a hemoglobin A1c concentration is warranted to assess for the presence of prediabetes or DM.² Many patients with PCOS have dyslipidemia, manifested through low high-density lipoprotein cholesterol levels and elevated low-density lipoprotein cholesterol levels, and a lipid panel assessment may be indicated. Among patients with PCOS, the most common lipid abnormality is a low high-density lipoprotein cholesterol level.¹⁷

Simplify the treatment of PCOS

Simplify treatment by counseling about lifestyle changes and prescribing an estrogen-progestin contraceptive, spironolactone, and metformin.

Most patients with PCOS have dysfunction in reproductive, metabolic, and dermatologic systems. For patients who are overweight or obese, lifestyle changes, including diet and exercise, that result in a 5% to 10% decrease in weight can improve metabolic balance, reduce circulating androgens, and increase menstrual frequency.¹⁸ For patients with PCOS and weight issues, referral to nutrition counseling or a full-service weight loss program can be very beneficial. In addition to lifestyle changes, patients with PCOS benefit from treatment with estrogen-progestin medications, spironolactone, and metformin.

Combination estrogen-progestin medications will lower LH secretion, decrease ovarian androgen production, increase SHBG production, decrease free testosterone levels and, if given cyclically, cause regular withdrawal bleeding.¹⁹ Spironolactone is an antiandrogen, which blocks the intracellular action of dihydrotestosterone and improves hirsutism and acne. Spironolactone also modestly decreases circulating levels of testosterone and DHEAS.²⁰ For patients with metabolic problems, including insulin resistance and obesity, weight loss and/or treatment with metformin can help improve metabolic balance, which may result in restoration of ovulatory menses.^21,22 Metformin can be effective in restoring ovulatory menses in both obese and lean patients with PCOS.²² The most common dermatologic problem caused by PCOS are hirsutism and acne. Both combination estrogen-progestin medications and spironolactone are effective treatments for hirsutism and acne.²³

Estrogen-progestin hormones, spironolactone, and metformin are low-cost medications for the treatment of PCOS. Additional high-cost options for treatment of PCOS in obese patients include bariatric surgery and glucagon-like peptide (GLP-1) agonist medications (liraglutide and exenatide). For patients with PCOS and a body mass index (BMI) ≥ 35 kg/m², bariatric surgery often results in sufficient weight loss to resolve the patient’s hyperandrogenism and oligo-ovulation, restoring spontaneous ovulatory cycles.²⁴ In a study of more than 1,000 patients with: PCOS; mean BMI, 44 kg/m²; mean age, 31 years who were followed post-bariatric surgery for 5 years, > 90% of patients reported reductions in hirsutism and resumption of regular menses.²⁵ For patients with PCOS seeking fertility, bariatric surgery often results in spontaneous pregnancy and live birth.²⁶ GLP-1 agonists, including liraglutide or exenatide with or without metformin are effective in reducing weight, decreasing androgen levels, and restoring ovulatory menses.^27,28

In my practice, I often prescribe 2 or 3 core medications for a patient with PCOS: 1) combination estrogen-progestin used cyclically or continuously, 2) spironolactone, and 3) metformin.¹⁹ Any estrogen-progestin contraceptive will suppress LH and ovarian androgen production; however, in the treatment of patients with PCOS, I prefer to use an estrogen-progestin combination that does not contain the androgenic progestin levonorgestrel.²⁹ For the treatment of PCOS, I prefer to use an estrogen-progestin contraceptive with a non-androgenic progestin such as drospirenone, desogestrel, or gestodene. I routinely prescribe spironolactone at a dose of 100 mg, once daily, a dose near the top of the dose-response curve. A daily dose ≤ 50 mg of spironolactone is subtherapeutic for the treatment of hirsutism. A daily dose of 200 mg of spironolactone may cause bothersome breakthrough bleeding. When prescribing metformin, I usually recommend the extended-release formulation, at a dose of 750 mg with dinner. If well tolerated, I will increase the dose to 1,500 mg with dinner. Most of my patients with PCOS are taking a combination of 2 medications, either an estrogen-progestin contraceptive plus spironolactone or an estrogen-progestin contraceptive plus metformin.¹⁹ Some of my patients are taking all 3 medications. All 3 medications are very low cost.

For patients with PCOS and anovulatory infertility, letrozole treatment often results in ovulatory cycles and pregnancy with live birth. In obese PCOS patients, compared with clomiphene, letrozole results in superior live birth rates.³⁰ Unlike clomiphene, letrozole is not approved by the US Food and Drug Administration for the treatment of anovulatory infertility.

The diagnosis of PCOS is often delayed due to confusion about how to make the diagnosis.³¹ To simplify the diagnosis of PCOS and improve patient encounters for PCOS, I focus on 2 core criteria: hyperandrogenism and oligo-ovulation. I recommend against ordering ultrasound imaging to assess for the presence of a multifollicular ovary. To simplify the treatment of PCOS I frequently prescribe an estrogen-progestin contraceptive, spironolactone, and metformin. By simplifying the diagnosis and treatment of PCOS, ObGyns will reduce patient confusion, improve outcomes, and save health care resources. ●

The number of Americans hospitalized because of the flu has hit the highest levels the country has seen in at least a decade, the Centers for Disease Control and Prevention said.
 

But the number of deaths and outpatient visits for flu or flu-like illnesses was down slightly from the week before, the CDC said in its weekly FluView report.

There were almost 26,000 new hospital admissions involving laboratory-confirmed influenza over those 7 days, up by over 31% from the previous week, based on data from 5,000 hospitals in the HHS Protect system, which tracks and shares COVID-19 data.

The cumulative hospitalization rate for the 2022-2023 season is 26.0 per 100,000 people, the highest seen at this time of year since 2010-2011, the CDC said, based on data from its Influenza Hospitalization Surveillance Network, which includes hospitals in select counties in 13 states.

At this point in the 2019-2020 season, just before the COVID-19 pandemic began, the cumulative rate was 3.1 per 100,000 people, the CDC’s data show.

On the positive side, the proportion of outpatient visits for influenza-like illness dropped slightly to 7.2%, from 7.5% the week before. But these cases from the CDC’s Outpatient Influenza-like Illness Surveillance Network are not laboratory confirmed, so the data could include people with the flu, COVID-19, or respiratory syncytial virus. 

The number of confirmed flu deaths for the week of Nov. 27 to Dec. 3 also fell slightly from the last full week of November, 246 vs. 255, but the number of pediatric deaths rose from 2 to 7, and total deaths in children are already up to 21 for 2022-2023. That’s compared to 44 that were reported during all of the 2021-2022 season, the CDC said.

“So far this season, there have been at least 13 million illnesses, 120,000 hospitalizations, and 7,300 deaths from flu,” the agency estimated.

A version of this article first appeared on Medscape.com.

The number of Americans hospitalized because of the flu has hit the highest levels the country has seen in at least a decade, the Centers for Disease Control and Prevention said.
 

But the number of deaths and outpatient visits for flu or flu-like illnesses was down slightly from the week before, the CDC said in its weekly FluView report.

There were almost 26,000 new hospital admissions involving laboratory-confirmed influenza over those 7 days, up by over 31% from the previous week, based on data from 5,000 hospitals in the HHS Protect system, which tracks and shares COVID-19 data.

The cumulative hospitalization rate for the 2022-2023 season is 26.0 per 100,000 people, the highest seen at this time of year since 2010-2011, the CDC said, based on data from its Influenza Hospitalization Surveillance Network, which includes hospitals in select counties in 13 states.

At this point in the 2019-2020 season, just before the COVID-19 pandemic began, the cumulative rate was 3.1 per 100,000 people, the CDC’s data show.

On the positive side, the proportion of outpatient visits for influenza-like illness dropped slightly to 7.2%, from 7.5% the week before. But these cases from the CDC’s Outpatient Influenza-like Illness Surveillance Network are not laboratory confirmed, so the data could include people with the flu, COVID-19, or respiratory syncytial virus. 

The number of confirmed flu deaths for the week of Nov. 27 to Dec. 3 also fell slightly from the last full week of November, 246 vs. 255, but the number of pediatric deaths rose from 2 to 7, and total deaths in children are already up to 21 for 2022-2023. That’s compared to 44 that were reported during all of the 2021-2022 season, the CDC said.

“So far this season, there have been at least 13 million illnesses, 120,000 hospitalizations, and 7,300 deaths from flu,” the agency estimated.

A version of this article first appeared on Medscape.com.

The number of Americans hospitalized because of the flu has hit the highest levels the country has seen in at least a decade, the Centers for Disease Control and Prevention said.
 

But the number of deaths and outpatient visits for flu or flu-like illnesses was down slightly from the week before, the CDC said in its weekly FluView report.

There were almost 26,000 new hospital admissions involving laboratory-confirmed influenza over those 7 days, up by over 31% from the previous week, based on data from 5,000 hospitals in the HHS Protect system, which tracks and shares COVID-19 data.

The cumulative hospitalization rate for the 2022-2023 season is 26.0 per 100,000 people, the highest seen at this time of year since 2010-2011, the CDC said, based on data from its Influenza Hospitalization Surveillance Network, which includes hospitals in select counties in 13 states.

At this point in the 2019-2020 season, just before the COVID-19 pandemic began, the cumulative rate was 3.1 per 100,000 people, the CDC’s data show.

On the positive side, the proportion of outpatient visits for influenza-like illness dropped slightly to 7.2%, from 7.5% the week before. But these cases from the CDC’s Outpatient Influenza-like Illness Surveillance Network are not laboratory confirmed, so the data could include people with the flu, COVID-19, or respiratory syncytial virus. 

The number of confirmed flu deaths for the week of Nov. 27 to Dec. 3 also fell slightly from the last full week of November, 246 vs. 255, but the number of pediatric deaths rose from 2 to 7, and total deaths in children are already up to 21 for 2022-2023. That’s compared to 44 that were reported during all of the 2021-2022 season, the CDC said.

“So far this season, there have been at least 13 million illnesses, 120,000 hospitalizations, and 7,300 deaths from flu,” the agency estimated.

A version of this article first appeared on Medscape.com.

NASHVILLE, TENN. – Targeting relevant sleep problems for patients with refractory temporal lobe epilepsy (TLE) improves cognition, results of a new, double-blind, randomized controlled trial suggest.

Study findings show significant improvement in REM sleep and language scores for patients with TLE who took the cholinesterase inhibitor donepezil and better slow-wave sleep and memory scores for those who took the sleep aid zolpidem.

The results are “intriguing and surprising” and should encourage clinicians to “look for sleep abnormalities” in patients with uncontrolled epilepsy, study investigator Garima Shukla, MBBS, MD, DM, professor, division of neurology, department of medicine, Queens University, Kingston, Ont., told this news organization.

Daytime sleepiness could be a red flag in these patients, although it could mean they just have treatable sleep apnea, said Dr. Shukla. “But if they have very poor slow-wave sleep, we could try increasing its percentage by prescribing zolpidem.”

The findings were presented at the annual meeting of the American Epilepsy Society.

Sleep, cognitive disturbances common

Sleep disturbances and cognitive disturbances are common among patients with TLE. Executive function is affected in almost all patients with refractory epilepsy, and it’s “super common” that TLE patients have memory disturbances, said Dr. Shukla.

The study included 108 patients with refractory TLE who were awaiting surgery. The patients, who had no severe comorbidities, were randomly assigned to three groups; the final number in each group was 36.

Patients in group 1 received donepezil 10 mg in the morning and a placebo at night. (Donepezil is used to treat memory loss associated with Alzheimer’s disease.)

Those in group 2 received a placebo in the morning and zolpidem 6.25 mg at night. Group 3 patients received a placebo in the morning and again at night.

The mean age of the patients was 25.4, 27.1, and 27.6 years, and the percentage of men was 63.8%, 72.2%, and 63.8% in groups 1, 2, and 3, respectively.

In all groups, patients had been experiencing about three seizures per month. The median number of antiseizure medications was two in group 1 and three in both groups 2 and 3.

Researchers evaluated sleep using the Pittsburgh Sleep Quality Index, the Epsworth Sleepiness Scale, and video polysomnography and electroencephalography.

To assess executive function, they used the Trail A & B, Stroop, and forward and backward Digit Span tests. For memory, they used the Weschler Memory Scale, and for language, the Western Aphasia Battery. They conducted follow-up evaluations at 6 months.

The results showed significant improvement in the percentage of rapid eye movement (REM) sleep in group 1 (from 14.81 at baseline to 18.21 at 6 months). In this group, the number of patients whose REM sleep percentage was less than 15 dropped significantly from 29 (of 36) to 10.

In group 2, sleep-onset latency significantly improved, and the percentage of N3 (slow-wave) sleep stage increased significantly from 25.27 to 28.74.

Regarding cognitive outcomes, backward Digit Span was significantly improved for patients in group 1. In this group, there was also a significant reduction in the time taken for Stroop A test, and there was significant improvement in language.

In group 2, there was a significant improvement in verbal and visual memory scores. There were no significant changes in group 3.

The increase in REM sleep percentage in group 1 strongly correlated with increased language and executive function scores. Similarly, in group 2, the increase in N3 sleep percentage strongly correlated with an increase in verbal memory scores.

On the basis of these observations, giving a small dose of zolpidem to a patient with “acceptable” REM sleep but very little slow-wave sleep may boost the patient’s non-REM sleep, said Dr. Shukla. “By improving non-REM sleep percentage, we will possibly help memory consolidation.”

Dr. Shukla sees this study as “a stepping-stone” to larger, multicenter trials testing “the effect of zolpidem through its impact on improving non-REM sleep percentage consolidation and its impact on memory.”

This idea veers somewhat from the traditional idea that REM sleep plays a greater role in memory consolidation, she said. “We actually found it correlates very well with language, which we have also seen in some of our anecdotal case reports.”

Patients whose language scores are very poor are “the population I would pick to target REM sleep through donepezil,” said Dr. Shukla.

‘Encouraging’ findings

Commenting for this news organization, Daniel Goldenholz, MD, PhD, assistant professor, Harvard Beth Israel Deaconess Medical Center, Boston, praised the study design.

“It allows for comparison between different treatments, as well as a placebo control group,” said Dr. Goldenholz, who added, “There appears to be good follow-up” as well.

The fact that medication may provide some cognitive benefit for patients with TLE is “very encouraging,” he said.

He noted many patients with TLE complain of memory or language problems. “So, this is a major concern.”

However, he cautioned about side effects. “Putting all temporal lobe epilepsy patients who say that they have memory problems or language problems on these medications could have some serious consequences.”

The study was funded by a Department of Health Research grant from the government of India. Dr. Goldenholz is on the advisory board for epilepsy AI, Eyzs, and Magic Leap.

A version of this article first appeared on Medscape.com.

NASHVILLE, TENN. – Targeting relevant sleep problems for patients with refractory temporal lobe epilepsy (TLE) improves cognition, results of a new, double-blind, randomized controlled trial suggest.

Study findings show significant improvement in REM sleep and language scores for patients with TLE who took the cholinesterase inhibitor donepezil and better slow-wave sleep and memory scores for those who took the sleep aid zolpidem.

The results are “intriguing and surprising” and should encourage clinicians to “look for sleep abnormalities” in patients with uncontrolled epilepsy, study investigator Garima Shukla, MBBS, MD, DM, professor, division of neurology, department of medicine, Queens University, Kingston, Ont., told this news organization.

Daytime sleepiness could be a red flag in these patients, although it could mean they just have treatable sleep apnea, said Dr. Shukla. “But if they have very poor slow-wave sleep, we could try increasing its percentage by prescribing zolpidem.”

The findings were presented at the annual meeting of the American Epilepsy Society.

Sleep, cognitive disturbances common

Sleep disturbances and cognitive disturbances are common among patients with TLE. Executive function is affected in almost all patients with refractory epilepsy, and it’s “super common” that TLE patients have memory disturbances, said Dr. Shukla.

The study included 108 patients with refractory TLE who were awaiting surgery. The patients, who had no severe comorbidities, were randomly assigned to three groups; the final number in each group was 36.

Patients in group 1 received donepezil 10 mg in the morning and a placebo at night. (Donepezil is used to treat memory loss associated with Alzheimer’s disease.)

Those in group 2 received a placebo in the morning and zolpidem 6.25 mg at night. Group 3 patients received a placebo in the morning and again at night.

The mean age of the patients was 25.4, 27.1, and 27.6 years, and the percentage of men was 63.8%, 72.2%, and 63.8% in groups 1, 2, and 3, respectively.

In all groups, patients had been experiencing about three seizures per month. The median number of antiseizure medications was two in group 1 and three in both groups 2 and 3.

Researchers evaluated sleep using the Pittsburgh Sleep Quality Index, the Epsworth Sleepiness Scale, and video polysomnography and electroencephalography.

To assess executive function, they used the Trail A & B, Stroop, and forward and backward Digit Span tests. For memory, they used the Weschler Memory Scale, and for language, the Western Aphasia Battery. They conducted follow-up evaluations at 6 months.

The results showed significant improvement in the percentage of rapid eye movement (REM) sleep in group 1 (from 14.81 at baseline to 18.21 at 6 months). In this group, the number of patients whose REM sleep percentage was less than 15 dropped significantly from 29 (of 36) to 10.

In group 2, sleep-onset latency significantly improved, and the percentage of N3 (slow-wave) sleep stage increased significantly from 25.27 to 28.74.

Regarding cognitive outcomes, backward Digit Span was significantly improved for patients in group 1. In this group, there was also a significant reduction in the time taken for Stroop A test, and there was significant improvement in language.

In group 2, there was a significant improvement in verbal and visual memory scores. There were no significant changes in group 3.

The increase in REM sleep percentage in group 1 strongly correlated with increased language and executive function scores. Similarly, in group 2, the increase in N3 sleep percentage strongly correlated with an increase in verbal memory scores.

On the basis of these observations, giving a small dose of zolpidem to a patient with “acceptable” REM sleep but very little slow-wave sleep may boost the patient’s non-REM sleep, said Dr. Shukla. “By improving non-REM sleep percentage, we will possibly help memory consolidation.”

Dr. Shukla sees this study as “a stepping-stone” to larger, multicenter trials testing “the effect of zolpidem through its impact on improving non-REM sleep percentage consolidation and its impact on memory.”

This idea veers somewhat from the traditional idea that REM sleep plays a greater role in memory consolidation, she said. “We actually found it correlates very well with language, which we have also seen in some of our anecdotal case reports.”

Patients whose language scores are very poor are “the population I would pick to target REM sleep through donepezil,” said Dr. Shukla.

‘Encouraging’ findings

Commenting for this news organization, Daniel Goldenholz, MD, PhD, assistant professor, Harvard Beth Israel Deaconess Medical Center, Boston, praised the study design.

“It allows for comparison between different treatments, as well as a placebo control group,” said Dr. Goldenholz, who added, “There appears to be good follow-up” as well.

The fact that medication may provide some cognitive benefit for patients with TLE is “very encouraging,” he said.

He noted many patients with TLE complain of memory or language problems. “So, this is a major concern.”

However, he cautioned about side effects. “Putting all temporal lobe epilepsy patients who say that they have memory problems or language problems on these medications could have some serious consequences.”

The study was funded by a Department of Health Research grant from the government of India. Dr. Goldenholz is on the advisory board for epilepsy AI, Eyzs, and Magic Leap.

A version of this article first appeared on Medscape.com.

NASHVILLE, TENN. – Targeting relevant sleep problems for patients with refractory temporal lobe epilepsy (TLE) improves cognition, results of a new, double-blind, randomized controlled trial suggest.

Study findings show significant improvement in REM sleep and language scores for patients with TLE who took the cholinesterase inhibitor donepezil and better slow-wave sleep and memory scores for those who took the sleep aid zolpidem.

The results are “intriguing and surprising” and should encourage clinicians to “look for sleep abnormalities” in patients with uncontrolled epilepsy, study investigator Garima Shukla, MBBS, MD, DM, professor, division of neurology, department of medicine, Queens University, Kingston, Ont., told this news organization.

Daytime sleepiness could be a red flag in these patients, although it could mean they just have treatable sleep apnea, said Dr. Shukla. “But if they have very poor slow-wave sleep, we could try increasing its percentage by prescribing zolpidem.”

The findings were presented at the annual meeting of the American Epilepsy Society.

Sleep, cognitive disturbances common

Sleep disturbances and cognitive disturbances are common among patients with TLE. Executive function is affected in almost all patients with refractory epilepsy, and it’s “super common” that TLE patients have memory disturbances, said Dr. Shukla.

The study included 108 patients with refractory TLE who were awaiting surgery. The patients, who had no severe comorbidities, were randomly assigned to three groups; the final number in each group was 36.

Patients in group 1 received donepezil 10 mg in the morning and a placebo at night. (Donepezil is used to treat memory loss associated with Alzheimer’s disease.)

Those in group 2 received a placebo in the morning and zolpidem 6.25 mg at night. Group 3 patients received a placebo in the morning and again at night.

The mean age of the patients was 25.4, 27.1, and 27.6 years, and the percentage of men was 63.8%, 72.2%, and 63.8% in groups 1, 2, and 3, respectively.

In all groups, patients had been experiencing about three seizures per month. The median number of antiseizure medications was two in group 1 and three in both groups 2 and 3.

Researchers evaluated sleep using the Pittsburgh Sleep Quality Index, the Epsworth Sleepiness Scale, and video polysomnography and electroencephalography.

To assess executive function, they used the Trail A & B, Stroop, and forward and backward Digit Span tests. For memory, they used the Weschler Memory Scale, and for language, the Western Aphasia Battery. They conducted follow-up evaluations at 6 months.

The results showed significant improvement in the percentage of rapid eye movement (REM) sleep in group 1 (from 14.81 at baseline to 18.21 at 6 months). In this group, the number of patients whose REM sleep percentage was less than 15 dropped significantly from 29 (of 36) to 10.

In group 2, sleep-onset latency significantly improved, and the percentage of N3 (slow-wave) sleep stage increased significantly from 25.27 to 28.74.

Regarding cognitive outcomes, backward Digit Span was significantly improved for patients in group 1. In this group, there was also a significant reduction in the time taken for Stroop A test, and there was significant improvement in language.

In group 2, there was a significant improvement in verbal and visual memory scores. There were no significant changes in group 3.

The increase in REM sleep percentage in group 1 strongly correlated with increased language and executive function scores. Similarly, in group 2, the increase in N3 sleep percentage strongly correlated with an increase in verbal memory scores.

On the basis of these observations, giving a small dose of zolpidem to a patient with “acceptable” REM sleep but very little slow-wave sleep may boost the patient’s non-REM sleep, said Dr. Shukla. “By improving non-REM sleep percentage, we will possibly help memory consolidation.”

Dr. Shukla sees this study as “a stepping-stone” to larger, multicenter trials testing “the effect of zolpidem through its impact on improving non-REM sleep percentage consolidation and its impact on memory.”

This idea veers somewhat from the traditional idea that REM sleep plays a greater role in memory consolidation, she said. “We actually found it correlates very well with language, which we have also seen in some of our anecdotal case reports.”

Patients whose language scores are very poor are “the population I would pick to target REM sleep through donepezil,” said Dr. Shukla.

‘Encouraging’ findings

Commenting for this news organization, Daniel Goldenholz, MD, PhD, assistant professor, Harvard Beth Israel Deaconess Medical Center, Boston, praised the study design.

“It allows for comparison between different treatments, as well as a placebo control group,” said Dr. Goldenholz, who added, “There appears to be good follow-up” as well.

The fact that medication may provide some cognitive benefit for patients with TLE is “very encouraging,” he said.

He noted many patients with TLE complain of memory or language problems. “So, this is a major concern.”

However, he cautioned about side effects. “Putting all temporal lobe epilepsy patients who say that they have memory problems or language problems on these medications could have some serious consequences.”

The study was funded by a Department of Health Research grant from the government of India. Dr. Goldenholz is on the advisory board for epilepsy AI, Eyzs, and Magic Leap.

A version of this article first appeared on Medscape.com.

A healthier lifestyle mitigated the impact of genetic factors on the risk of thyroid cancer, in a study based on data from more than 260,000 individuals.

Thyroid cancer has increased globally in recent years and ranks 9th among 36 cancers worldwide, at a considerable cost to health care systems, wrote Xiuming Feng of Guangxi Medical University, Nanning, Guangxi, China, and colleagues.

SciePro/Science Source

Both genetic and lifestyle factors are related to thyroid cancer; previous research suggests a heritability of about 50%, but data on the impact of modifiable lifestyle factors on thyroid cancer are limited, the researchers said.

In a prospective cohort study published in JAMA Network Open, the researchers used data from the UK Biobank and recruited adults aged 40-69 years during March 2006–October 2010. The final study population included 264,956 individuals of European descent. The median age of the participants was 57 years, and 52% were women.

Data on lifestyle behaviors were collected using interviews and questionnaires. The researchers constructed a total lifestyle score based on five variables: diet, physical activity, weight, smoking, and alcohol consumption. Each variable was assigned a score of 0 or 1, with 1 being favorable lifestyle behavior. Lifestyle was divided into three categories: unfavorable (scores 0-1), intermediate (score 2), and favorable (scores 3-5).

Each individual’s polygenic risk score (PRS) was categorized as low, intermediate, or high based on a meta–genome-wide association study of three cohorts.

The main outcome was the development of thyroid cancer.

The researchers identified 423 incident thyroid cancer cases over a median follow-up of 11.1 years.

Overall, higher PRSs were significantly associated with thyroid cancer (hazard ratio, 2.25; 95% confidence interval [CI], 1.91-2.64; P < .00001) as was an unfavorable lifestyle score (HR, 1.93; 95% CI, 1.50-2.49; P < .001 for trend).

An unfavorable lifestyle was significantly associated with thyroid cancer in the highest PRS group, and individuals with high PRS and unfavorable lifestyle had a nearly fivefold increased risk of thyroid cancer (HR, 4.89; 95% CI, 3.03-7.91; P < .001). By extension, “Adherence to a healthier lifestyle could decrease the incidence of thyroid cancer in individuals with a higher PRS,” the researchers wrote in their discussion.

The findings were limited by several factors, including the availability of only baseline lifestyle data, and lack of data on iodine intake, radiation exposure, experience, and family history, the researchers noted. Other limitations include the potential lack of generalizability to populations other than the individuals of European descent in the current study, they said.

However, the study is the first known to address the association among lifestyle, genetic factors, and risk of thyroid cancer, and was strengthened by the large study population, and the results suggest that lifestyle interventions may help reduce the risk of thyroid cancer in those with a genetic predisposition, they concluded.

Healthy living can make a difference

The incidence of thyroid cancer has increased annually, and exploring the possible risk factors could prevent the occurrence of thyroid cancer, corresponding author Xiaobo Yang, PhD, said in an interview.

Previous studies have reported that thyroid cancer is related to genetics and lifestyle, said Dr. Yang. “However, whether healthy lifestyle was associated with thyroid cancer risk and could attenuate the impact of genetic variants on thyroid cancer remains equivocal; therefore, it is crucial to determine the associations between genetic and lifestyle with thyroid cancer,” he said.

“To our surprise, we found that adherence to healthier lifestyle also could reduce the risk of thyroid cancer in those with high genetic predispositions,” said Dr. Yang. “The findings highlight the potential role of lifestyle interventions on thyroid cancer, especially in those with high genetic risk, because the heritability of thyroid cancer was very high, approximately 50%,” he said. “More attention should be paid to the role of healthier lifestyle in the prevention of cancer,” he added.

“Adherence to a healthier lifestyle could decrease the risk of thyroid cancer, which is the important message for clinicians,” said Dr. Yang. “It is not too soon to comment on implications for clinical practice, because many studies have maintained the consistent comment that healthier lifestyle could prevent the occurrence of cancer,” he said.

The relationship between sex-specific lifestyle factors such as smoking and alcohol use and thyroid cancer remains uncertain, and more research is needed to validate these associations, Dr. Yang said. More research also is needed to confirm the complex mechanism between lifestyle and genetics in thyroid cancer, he added.

The study was supported by the National Key R&D Program of China and the National Natural Science Foundation of China. The researchers had no financial conflicts to disclose.

A healthier lifestyle mitigated the impact of genetic factors on the risk of thyroid cancer, in a study based on data from more than 260,000 individuals.

Thyroid cancer has increased globally in recent years and ranks 9th among 36 cancers worldwide, at a considerable cost to health care systems, wrote Xiuming Feng of Guangxi Medical University, Nanning, Guangxi, China, and colleagues.

SciePro/Science Source

Both genetic and lifestyle factors are related to thyroid cancer; previous research suggests a heritability of about 50%, but data on the impact of modifiable lifestyle factors on thyroid cancer are limited, the researchers said.

In a prospective cohort study published in JAMA Network Open, the researchers used data from the UK Biobank and recruited adults aged 40-69 years during March 2006–October 2010. The final study population included 264,956 individuals of European descent. The median age of the participants was 57 years, and 52% were women.

Data on lifestyle behaviors were collected using interviews and questionnaires. The researchers constructed a total lifestyle score based on five variables: diet, physical activity, weight, smoking, and alcohol consumption. Each variable was assigned a score of 0 or 1, with 1 being favorable lifestyle behavior. Lifestyle was divided into three categories: unfavorable (scores 0-1), intermediate (score 2), and favorable (scores 3-5).

Each individual’s polygenic risk score (PRS) was categorized as low, intermediate, or high based on a meta–genome-wide association study of three cohorts.

The main outcome was the development of thyroid cancer.

The researchers identified 423 incident thyroid cancer cases over a median follow-up of 11.1 years.

Overall, higher PRSs were significantly associated with thyroid cancer (hazard ratio, 2.25; 95% confidence interval [CI], 1.91-2.64; P < .00001) as was an unfavorable lifestyle score (HR, 1.93; 95% CI, 1.50-2.49; P < .001 for trend).

An unfavorable lifestyle was significantly associated with thyroid cancer in the highest PRS group, and individuals with high PRS and unfavorable lifestyle had a nearly fivefold increased risk of thyroid cancer (HR, 4.89; 95% CI, 3.03-7.91; P < .001). By extension, “Adherence to a healthier lifestyle could decrease the incidence of thyroid cancer in individuals with a higher PRS,” the researchers wrote in their discussion.

The findings were limited by several factors, including the availability of only baseline lifestyle data, and lack of data on iodine intake, radiation exposure, experience, and family history, the researchers noted. Other limitations include the potential lack of generalizability to populations other than the individuals of European descent in the current study, they said.

However, the study is the first known to address the association among lifestyle, genetic factors, and risk of thyroid cancer, and was strengthened by the large study population, and the results suggest that lifestyle interventions may help reduce the risk of thyroid cancer in those with a genetic predisposition, they concluded.

Healthy living can make a difference

The incidence of thyroid cancer has increased annually, and exploring the possible risk factors could prevent the occurrence of thyroid cancer, corresponding author Xiaobo Yang, PhD, said in an interview.

Previous studies have reported that thyroid cancer is related to genetics and lifestyle, said Dr. Yang. “However, whether healthy lifestyle was associated with thyroid cancer risk and could attenuate the impact of genetic variants on thyroid cancer remains equivocal; therefore, it is crucial to determine the associations between genetic and lifestyle with thyroid cancer,” he said.

“To our surprise, we found that adherence to healthier lifestyle also could reduce the risk of thyroid cancer in those with high genetic predispositions,” said Dr. Yang. “The findings highlight the potential role of lifestyle interventions on thyroid cancer, especially in those with high genetic risk, because the heritability of thyroid cancer was very high, approximately 50%,” he said. “More attention should be paid to the role of healthier lifestyle in the prevention of cancer,” he added.

“Adherence to a healthier lifestyle could decrease the risk of thyroid cancer, which is the important message for clinicians,” said Dr. Yang. “It is not too soon to comment on implications for clinical practice, because many studies have maintained the consistent comment that healthier lifestyle could prevent the occurrence of cancer,” he said.

The relationship between sex-specific lifestyle factors such as smoking and alcohol use and thyroid cancer remains uncertain, and more research is needed to validate these associations, Dr. Yang said. More research also is needed to confirm the complex mechanism between lifestyle and genetics in thyroid cancer, he added.

The study was supported by the National Key R&D Program of China and the National Natural Science Foundation of China. The researchers had no financial conflicts to disclose.

A healthier lifestyle mitigated the impact of genetic factors on the risk of thyroid cancer, in a study based on data from more than 260,000 individuals.

Thyroid cancer has increased globally in recent years and ranks 9th among 36 cancers worldwide, at a considerable cost to health care systems, wrote Xiuming Feng of Guangxi Medical University, Nanning, Guangxi, China, and colleagues.

SciePro/Science Source

Both genetic and lifestyle factors are related to thyroid cancer; previous research suggests a heritability of about 50%, but data on the impact of modifiable lifestyle factors on thyroid cancer are limited, the researchers said.

In a prospective cohort study published in JAMA Network Open, the researchers used data from the UK Biobank and recruited adults aged 40-69 years during March 2006–October 2010. The final study population included 264,956 individuals of European descent. The median age of the participants was 57 years, and 52% were women.

Data on lifestyle behaviors were collected using interviews and questionnaires. The researchers constructed a total lifestyle score based on five variables: diet, physical activity, weight, smoking, and alcohol consumption. Each variable was assigned a score of 0 or 1, with 1 being favorable lifestyle behavior. Lifestyle was divided into three categories: unfavorable (scores 0-1), intermediate (score 2), and favorable (scores 3-5).

Each individual’s polygenic risk score (PRS) was categorized as low, intermediate, or high based on a meta–genome-wide association study of three cohorts.

The main outcome was the development of thyroid cancer.

The researchers identified 423 incident thyroid cancer cases over a median follow-up of 11.1 years.

Overall, higher PRSs were significantly associated with thyroid cancer (hazard ratio, 2.25; 95% confidence interval [CI], 1.91-2.64; P < .00001) as was an unfavorable lifestyle score (HR, 1.93; 95% CI, 1.50-2.49; P < .001 for trend).

An unfavorable lifestyle was significantly associated with thyroid cancer in the highest PRS group, and individuals with high PRS and unfavorable lifestyle had a nearly fivefold increased risk of thyroid cancer (HR, 4.89; 95% CI, 3.03-7.91; P < .001). By extension, “Adherence to a healthier lifestyle could decrease the incidence of thyroid cancer in individuals with a higher PRS,” the researchers wrote in their discussion.

The findings were limited by several factors, including the availability of only baseline lifestyle data, and lack of data on iodine intake, radiation exposure, experience, and family history, the researchers noted. Other limitations include the potential lack of generalizability to populations other than the individuals of European descent in the current study, they said.

However, the study is the first known to address the association among lifestyle, genetic factors, and risk of thyroid cancer, and was strengthened by the large study population, and the results suggest that lifestyle interventions may help reduce the risk of thyroid cancer in those with a genetic predisposition, they concluded.

Healthy living can make a difference

The incidence of thyroid cancer has increased annually, and exploring the possible risk factors could prevent the occurrence of thyroid cancer, corresponding author Xiaobo Yang, PhD, said in an interview.

Previous studies have reported that thyroid cancer is related to genetics and lifestyle, said Dr. Yang. “However, whether healthy lifestyle was associated with thyroid cancer risk and could attenuate the impact of genetic variants on thyroid cancer remains equivocal; therefore, it is crucial to determine the associations between genetic and lifestyle with thyroid cancer,” he said.

“To our surprise, we found that adherence to healthier lifestyle also could reduce the risk of thyroid cancer in those with high genetic predispositions,” said Dr. Yang. “The findings highlight the potential role of lifestyle interventions on thyroid cancer, especially in those with high genetic risk, because the heritability of thyroid cancer was very high, approximately 50%,” he said. “More attention should be paid to the role of healthier lifestyle in the prevention of cancer,” he added.

“Adherence to a healthier lifestyle could decrease the risk of thyroid cancer, which is the important message for clinicians,” said Dr. Yang. “It is not too soon to comment on implications for clinical practice, because many studies have maintained the consistent comment that healthier lifestyle could prevent the occurrence of cancer,” he said.

The relationship between sex-specific lifestyle factors such as smoking and alcohol use and thyroid cancer remains uncertain, and more research is needed to validate these associations, Dr. Yang said. More research also is needed to confirm the complex mechanism between lifestyle and genetics in thyroid cancer, he added.

The study was supported by the National Key R&D Program of China and the National Natural Science Foundation of China. The researchers had no financial conflicts to disclose.

In a new attempt to replenish the constantly draining pool of mental health professionals, the US Department of Veterans Affairs (VA) is establishing a scholarship program for students pursuing graduate degrees in psychology, social work, marriage and family therapy, or mental health counseling. 

Staffing shortages in mental health have reached crisis proportions across the country, driven in part by 3 years of the pandemic. The VA is not immune. VA shortages go back a long way and have never really been resolved. In 2012, for instance, the VA announced that it planned to expand its mental health staff by nearly 10%, hiring about 1600 additional psychiatrists, psychologists, social workers, and other mental health clinicians to reduce long wait times at many VA medical centers. And indeed, between 2018 and 2021, the number of severe shortages reported declined from 3,068 to 2,152.

However, in 2021, the VA Office of the Inspector General (OIG) released its eighth report in a series on occupational staffing shortages for the 139 facilities. According to the OIG report, 136 facilities reported at least 1 severe occupational staffing shortage, an increase from 132 in fiscal year 2020. Psychiatry was the most frequently reported clinical occupation with severe staffing shortages.

In July 2022, the OIG released its ninth report and the fifth to identify “severe occupational staffing shortages” for VA facilities. The OIG found severe shortages were widespread: Facilities identified 2,622 severe occupational staffing shortages across 285 occupations, which ended a downward trend. Of the 139 facilities, 73 identified severe shortage in psychology, 71 listed psychiatry, 44 listed social work, and 30 listed registered nurse staff for inpatient mental health sections. 

In fact, although the Veterans Health Administration has been increasing the number of staff since 2017, psychology and psychiatry have remained in the top 10 most frequently reported severe shortages annually. 

The scholarship program, expected to start in summer 2023, will fund up to 2 years of graduate studies. After completing their degrees, the mental health professionals will serve full time for 6 years at one of the VA’s Vet Centers, specifically in underserved areas and in states with a per capita population of more than 5% veterans. Vet Centers are community-based outpatient counseling centers that provide a wide range of social and psychological services. 

“In 300 communities across the country, Vet Centers provide veterans, service members, and their families with quick and easy access to the mental health care they need and deserve,” said VA Secretary Denis McDonough. “These scholarships will help VA ensure all veterans and service members—including those in historically underserved areas—have access to Vet Centers with highly qualified, trained and compassionate staff.” 

The VA has posted a final rule for public inspection in the Federal Register 86 FR 81094 to create the scholarship program. 

In a new attempt to replenish the constantly draining pool of mental health professionals, the US Department of Veterans Affairs (VA) is establishing a scholarship program for students pursuing graduate degrees in psychology, social work, marriage and family therapy, or mental health counseling. 

Staffing shortages in mental health have reached crisis proportions across the country, driven in part by 3 years of the pandemic. The VA is not immune. VA shortages go back a long way and have never really been resolved. In 2012, for instance, the VA announced that it planned to expand its mental health staff by nearly 10%, hiring about 1600 additional psychiatrists, psychologists, social workers, and other mental health clinicians to reduce long wait times at many VA medical centers. And indeed, between 2018 and 2021, the number of severe shortages reported declined from 3,068 to 2,152.

However, in 2021, the VA Office of the Inspector General (OIG) released its eighth report in a series on occupational staffing shortages for the 139 facilities. According to the OIG report, 136 facilities reported at least 1 severe occupational staffing shortage, an increase from 132 in fiscal year 2020. Psychiatry was the most frequently reported clinical occupation with severe staffing shortages.

In July 2022, the OIG released its ninth report and the fifth to identify “severe occupational staffing shortages” for VA facilities. The OIG found severe shortages were widespread: Facilities identified 2,622 severe occupational staffing shortages across 285 occupations, which ended a downward trend. Of the 139 facilities, 73 identified severe shortage in psychology, 71 listed psychiatry, 44 listed social work, and 30 listed registered nurse staff for inpatient mental health sections. 

In fact, although the Veterans Health Administration has been increasing the number of staff since 2017, psychology and psychiatry have remained in the top 10 most frequently reported severe shortages annually. 

The scholarship program, expected to start in summer 2023, will fund up to 2 years of graduate studies. After completing their degrees, the mental health professionals will serve full time for 6 years at one of the VA’s Vet Centers, specifically in underserved areas and in states with a per capita population of more than 5% veterans. Vet Centers are community-based outpatient counseling centers that provide a wide range of social and psychological services. 

“In 300 communities across the country, Vet Centers provide veterans, service members, and their families with quick and easy access to the mental health care they need and deserve,” said VA Secretary Denis McDonough. “These scholarships will help VA ensure all veterans and service members—including those in historically underserved areas—have access to Vet Centers with highly qualified, trained and compassionate staff.” 

The VA has posted a final rule for public inspection in the Federal Register 86 FR 81094 to create the scholarship program. 

In a new attempt to replenish the constantly draining pool of mental health professionals, the US Department of Veterans Affairs (VA) is establishing a scholarship program for students pursuing graduate degrees in psychology, social work, marriage and family therapy, or mental health counseling. 

Staffing shortages in mental health have reached crisis proportions across the country, driven in part by 3 years of the pandemic. The VA is not immune. VA shortages go back a long way and have never really been resolved. In 2012, for instance, the VA announced that it planned to expand its mental health staff by nearly 10%, hiring about 1600 additional psychiatrists, psychologists, social workers, and other mental health clinicians to reduce long wait times at many VA medical centers. And indeed, between 2018 and 2021, the number of severe shortages reported declined from 3,068 to 2,152.

However, in 2021, the VA Office of the Inspector General (OIG) released its eighth report in a series on occupational staffing shortages for the 139 facilities. According to the OIG report, 136 facilities reported at least 1 severe occupational staffing shortage, an increase from 132 in fiscal year 2020. Psychiatry was the most frequently reported clinical occupation with severe staffing shortages.

In July 2022, the OIG released its ninth report and the fifth to identify “severe occupational staffing shortages” for VA facilities. The OIG found severe shortages were widespread: Facilities identified 2,622 severe occupational staffing shortages across 285 occupations, which ended a downward trend. Of the 139 facilities, 73 identified severe shortage in psychology, 71 listed psychiatry, 44 listed social work, and 30 listed registered nurse staff for inpatient mental health sections. 

In fact, although the Veterans Health Administration has been increasing the number of staff since 2017, psychology and psychiatry have remained in the top 10 most frequently reported severe shortages annually. 

The scholarship program, expected to start in summer 2023, will fund up to 2 years of graduate studies. After completing their degrees, the mental health professionals will serve full time for 6 years at one of the VA’s Vet Centers, specifically in underserved areas and in states with a per capita population of more than 5% veterans. Vet Centers are community-based outpatient counseling centers that provide a wide range of social and psychological services. 

“In 300 communities across the country, Vet Centers provide veterans, service members, and their families with quick and easy access to the mental health care they need and deserve,” said VA Secretary Denis McDonough. “These scholarships will help VA ensure all veterans and service members—including those in historically underserved areas—have access to Vet Centers with highly qualified, trained and compassionate staff.” 

The VA has posted a final rule for public inspection in the Federal Register 86 FR 81094 to create the scholarship program. 

Patients with ulcerative colitis who were treated with upadacitinib showed significant improvement in symptoms compared to placebo within days of starting treatment, according to results of a new study.

Immunosuppressants and biologics used to treat moderate to severe disease can vary in their response times from weeks to months, and some ambulatory patients fail to respond to these treatments, wrote Edward V. Loftus Jr., MD, of the Mayo Clinic, Rochester, Minn., and colleagues.

“The lack of effective, quick-acting therapies may lead patients to experience prolonged relapses, reduced quality of life, and a significant burden of illness,” the researchers said.

Upadacitinib, an oral, once-daily reversible JAK inhibitor, is approved by the Food and Drug Administration for patients with moderate to severe ulcerative colitis (UC) who have not responded to at least one tumor necrosis factor (TNF) blocker, but the time frame for response to upadacitinib has not been well studied, they said.

In a study published online in Clinical Gastroenterology and Hepatology, the researchers reviewed data from two phase 3 randomized, placebo-controlled induction trials, U-ACHIEVE Induction (NCT02819635) and U-ACCOMPLISH (NCT03653026), that assessed the safety and efficacy of a 45-mg daily dose of upadacitinib for managing symptoms of moderate to severe UC over an 8-week period.

The intent-to-treat analysis included 660 patients who had been randomized to received upadacitinib and 328 in the placebo group. Demographics were similar between the groups. Symptom improvement was based on changes in inflammatory markers high-sensitivity C-reactive protein (hs-CRP) and fecal calprotectin (FCP) measured at week 2. Quality of life was assessed at 2 and 8 weeks.

Between 1 and 3 days after starting treatment, significantly greater percentages of patients in the treatment arm achieved a reduction of at least 50% from baseline in hs-CRP (75.7% vs. 21.9%) and FCP (48.2% vs. 20.2%).

The significant differences in symptom improvement persisted for 14 days from the first dose.

Patients in the upadacitinib group also showed increased rates of clinical remission/response (26.9%/59.4%) based on Partial Mayo scores at week 2 compared with placebo patients (4.3%/22.3%). Treated patients showed significant improvements in quality of life at weeks 2 and 8.

In addition, patient-reported UC symptoms of stool frequency, rectal bleeding, abdominal pain, and bowel urgency improved significantly compared with placebo by day 3, the researchers noted. “In this study, upadacitinib led to absence of rectal bleeding by day 1 and absence of abdominal pain and bowel urgency by day 3 in a significant proportion of patients vs. placebo (all P < .05),” they said.

The findings were limited by the post hoc design, but reflect results of other studies, including those of the JAK inhibitor tofacitinib, the researchers noted. The results of the current study demonstrate the ability of upadacitinib to alleviate key UC symptoms as early as 1 day after the first dose, they concluded.
 

Need for rapid onset treatment

A majority of biologics used to treat IBD take weeks to months to exert an effect, “so it is crucial that a drug with more rapid onset of action become available,” Atsushi Sakuraba, MD, director of clinical trial/IBD research at the University of Chicago, said in an interview.

Dr. Sakuraba, who was not involved in the study, said he was surprised by the findings.

“It is amazing that upadacitinib started to show response in 1-3 days and showed superior rates of remission/response versus placebo by week 2,” he said.

“Clinicians treating IBD patients should take the time to response into consideration, because it leads to rapid improvement in quality of life and reduced need for steroids,” Dr. Sakuraba said. The current study findings need to be confirmed in real life studies, he cautioned.
 

Expanding clinical options

Jeffrey Berinstein, MD, of the University of Michigan, Ann Arbor, who was not involved with the study, said in an interview that he was not surprised by upadacitinib’s quick action, which supports what he has seen in clinical practice. “We now have post hoc data from the phase 3, multicenter induction trials ... to provide us with hard evidence to support our observations,” he noted.

The current study is important because many patients with UC can be very symptomatic, with rectal bleeding, diarrhea, urgency, and abdominal pain, he said in an interview.

“It is often critical to have a fast-acting medication to avoid worsening symptoms, hospitalization, and severe complications. This study shows that upadacitinib, a new oral small molecule that selectively inhibits JAK-1, works within 1 day to improve symptoms and within 2 weeks to improve CRP and fecal calprotectin,” he said.

The takeaway message to clinicians is that upadacitinib is effective, relatively safe, and fast-acting option for patients with UC who have previously failed an anti-TNF agent, he said.

Challenges remain, however.

“Despite this exciting new therapeutic, there is still significant research needed to break our current therapeutic efficacy ceiling and get more IBD patients into a stable and durable remission,” Dr. Berinstein said. “Additional research is needed to develop personalized treatment strategies to address the unique needs of individual patients and to guide optimal medical management.”

Dr. Berinstein and his team are exploring the use of upadacitinib on the sickest IBD patients, “those admitted to the hospital with acute severe ulcerative colitis,” he said. Emerging data from multiple academic centers suggest that “upadacitinib induction may be a viable treatment strategy for these very high-risk patients. Of course, large prospective trials will be needed to confirm this,” he added.

The study was funded by AbbVie, which markets upadacitinib (Rinvoq). Lead author Dr. Loftus and several study authors disclosed financial relationships with AbbVie and other companies. Dr. Sakuraba and Dr. Berinstein reported having no relevant financial conflicts.

Patients with ulcerative colitis who were treated with upadacitinib showed significant improvement in symptoms compared to placebo within days of starting treatment, according to results of a new study.

Immunosuppressants and biologics used to treat moderate to severe disease can vary in their response times from weeks to months, and some ambulatory patients fail to respond to these treatments, wrote Edward V. Loftus Jr., MD, of the Mayo Clinic, Rochester, Minn., and colleagues.

“The lack of effective, quick-acting therapies may lead patients to experience prolonged relapses, reduced quality of life, and a significant burden of illness,” the researchers said.

Upadacitinib, an oral, once-daily reversible JAK inhibitor, is approved by the Food and Drug Administration for patients with moderate to severe ulcerative colitis (UC) who have not responded to at least one tumor necrosis factor (TNF) blocker, but the time frame for response to upadacitinib has not been well studied, they said.

In a study published online in Clinical Gastroenterology and Hepatology, the researchers reviewed data from two phase 3 randomized, placebo-controlled induction trials, U-ACHIEVE Induction (NCT02819635) and U-ACCOMPLISH (NCT03653026), that assessed the safety and efficacy of a 45-mg daily dose of upadacitinib for managing symptoms of moderate to severe UC over an 8-week period.

The intent-to-treat analysis included 660 patients who had been randomized to received upadacitinib and 328 in the placebo group. Demographics were similar between the groups. Symptom improvement was based on changes in inflammatory markers high-sensitivity C-reactive protein (hs-CRP) and fecal calprotectin (FCP) measured at week 2. Quality of life was assessed at 2 and 8 weeks.

Between 1 and 3 days after starting treatment, significantly greater percentages of patients in the treatment arm achieved a reduction of at least 50% from baseline in hs-CRP (75.7% vs. 21.9%) and FCP (48.2% vs. 20.2%).

The significant differences in symptom improvement persisted for 14 days from the first dose.

Patients in the upadacitinib group also showed increased rates of clinical remission/response (26.9%/59.4%) based on Partial Mayo scores at week 2 compared with placebo patients (4.3%/22.3%). Treated patients showed significant improvements in quality of life at weeks 2 and 8.

In addition, patient-reported UC symptoms of stool frequency, rectal bleeding, abdominal pain, and bowel urgency improved significantly compared with placebo by day 3, the researchers noted. “In this study, upadacitinib led to absence of rectal bleeding by day 1 and absence of abdominal pain and bowel urgency by day 3 in a significant proportion of patients vs. placebo (all P < .05),” they said.

The findings were limited by the post hoc design, but reflect results of other studies, including those of the JAK inhibitor tofacitinib, the researchers noted. The results of the current study demonstrate the ability of upadacitinib to alleviate key UC symptoms as early as 1 day after the first dose, they concluded.
 

Need for rapid onset treatment

A majority of biologics used to treat IBD take weeks to months to exert an effect, “so it is crucial that a drug with more rapid onset of action become available,” Atsushi Sakuraba, MD, director of clinical trial/IBD research at the University of Chicago, said in an interview.

Dr. Sakuraba, who was not involved in the study, said he was surprised by the findings.

“It is amazing that upadacitinib started to show response in 1-3 days and showed superior rates of remission/response versus placebo by week 2,” he said.

“Clinicians treating IBD patients should take the time to response into consideration, because it leads to rapid improvement in quality of life and reduced need for steroids,” Dr. Sakuraba said. The current study findings need to be confirmed in real life studies, he cautioned.
 

Expanding clinical options

Jeffrey Berinstein, MD, of the University of Michigan, Ann Arbor, who was not involved with the study, said in an interview that he was not surprised by upadacitinib’s quick action, which supports what he has seen in clinical practice. “We now have post hoc data from the phase 3, multicenter induction trials ... to provide us with hard evidence to support our observations,” he noted.

The current study is important because many patients with UC can be very symptomatic, with rectal bleeding, diarrhea, urgency, and abdominal pain, he said in an interview.

“It is often critical to have a fast-acting medication to avoid worsening symptoms, hospitalization, and severe complications. This study shows that upadacitinib, a new oral small molecule that selectively inhibits JAK-1, works within 1 day to improve symptoms and within 2 weeks to improve CRP and fecal calprotectin,” he said.

The takeaway message to clinicians is that upadacitinib is effective, relatively safe, and fast-acting option for patients with UC who have previously failed an anti-TNF agent, he said.

Challenges remain, however.

“Despite this exciting new therapeutic, there is still significant research needed to break our current therapeutic efficacy ceiling and get more IBD patients into a stable and durable remission,” Dr. Berinstein said. “Additional research is needed to develop personalized treatment strategies to address the unique needs of individual patients and to guide optimal medical management.”

Dr. Berinstein and his team are exploring the use of upadacitinib on the sickest IBD patients, “those admitted to the hospital with acute severe ulcerative colitis,” he said. Emerging data from multiple academic centers suggest that “upadacitinib induction may be a viable treatment strategy for these very high-risk patients. Of course, large prospective trials will be needed to confirm this,” he added.

The study was funded by AbbVie, which markets upadacitinib (Rinvoq). Lead author Dr. Loftus and several study authors disclosed financial relationships with AbbVie and other companies. Dr. Sakuraba and Dr. Berinstein reported having no relevant financial conflicts.

Patients with ulcerative colitis who were treated with upadacitinib showed significant improvement in symptoms compared to placebo within days of starting treatment, according to results of a new study.

Immunosuppressants and biologics used to treat moderate to severe disease can vary in their response times from weeks to months, and some ambulatory patients fail to respond to these treatments, wrote Edward V. Loftus Jr., MD, of the Mayo Clinic, Rochester, Minn., and colleagues.

“The lack of effective, quick-acting therapies may lead patients to experience prolonged relapses, reduced quality of life, and a significant burden of illness,” the researchers said.

Upadacitinib, an oral, once-daily reversible JAK inhibitor, is approved by the Food and Drug Administration for patients with moderate to severe ulcerative colitis (UC) who have not responded to at least one tumor necrosis factor (TNF) blocker, but the time frame for response to upadacitinib has not been well studied, they said.

In a study published online in Clinical Gastroenterology and Hepatology, the researchers reviewed data from two phase 3 randomized, placebo-controlled induction trials, U-ACHIEVE Induction (NCT02819635) and U-ACCOMPLISH (NCT03653026), that assessed the safety and efficacy of a 45-mg daily dose of upadacitinib for managing symptoms of moderate to severe UC over an 8-week period.

The intent-to-treat analysis included 660 patients who had been randomized to received upadacitinib and 328 in the placebo group. Demographics were similar between the groups. Symptom improvement was based on changes in inflammatory markers high-sensitivity C-reactive protein (hs-CRP) and fecal calprotectin (FCP) measured at week 2. Quality of life was assessed at 2 and 8 weeks.

Between 1 and 3 days after starting treatment, significantly greater percentages of patients in the treatment arm achieved a reduction of at least 50% from baseline in hs-CRP (75.7% vs. 21.9%) and FCP (48.2% vs. 20.2%).

The significant differences in symptom improvement persisted for 14 days from the first dose.

Patients in the upadacitinib group also showed increased rates of clinical remission/response (26.9%/59.4%) based on Partial Mayo scores at week 2 compared with placebo patients (4.3%/22.3%). Treated patients showed significant improvements in quality of life at weeks 2 and 8.

In addition, patient-reported UC symptoms of stool frequency, rectal bleeding, abdominal pain, and bowel urgency improved significantly compared with placebo by day 3, the researchers noted. “In this study, upadacitinib led to absence of rectal bleeding by day 1 and absence of abdominal pain and bowel urgency by day 3 in a significant proportion of patients vs. placebo (all P < .05),” they said.

The findings were limited by the post hoc design, but reflect results of other studies, including those of the JAK inhibitor tofacitinib, the researchers noted. The results of the current study demonstrate the ability of upadacitinib to alleviate key UC symptoms as early as 1 day after the first dose, they concluded.
 

Need for rapid onset treatment

A majority of biologics used to treat IBD take weeks to months to exert an effect, “so it is crucial that a drug with more rapid onset of action become available,” Atsushi Sakuraba, MD, director of clinical trial/IBD research at the University of Chicago, said in an interview.

Dr. Sakuraba, who was not involved in the study, said he was surprised by the findings.

“It is amazing that upadacitinib started to show response in 1-3 days and showed superior rates of remission/response versus placebo by week 2,” he said.

“Clinicians treating IBD patients should take the time to response into consideration, because it leads to rapid improvement in quality of life and reduced need for steroids,” Dr. Sakuraba said. The current study findings need to be confirmed in real life studies, he cautioned.
 

Expanding clinical options

Jeffrey Berinstein, MD, of the University of Michigan, Ann Arbor, who was not involved with the study, said in an interview that he was not surprised by upadacitinib’s quick action, which supports what he has seen in clinical practice. “We now have post hoc data from the phase 3, multicenter induction trials ... to provide us with hard evidence to support our observations,” he noted.

The current study is important because many patients with UC can be very symptomatic, with rectal bleeding, diarrhea, urgency, and abdominal pain, he said in an interview.

“It is often critical to have a fast-acting medication to avoid worsening symptoms, hospitalization, and severe complications. This study shows that upadacitinib, a new oral small molecule that selectively inhibits JAK-1, works within 1 day to improve symptoms and within 2 weeks to improve CRP and fecal calprotectin,” he said.

The takeaway message to clinicians is that upadacitinib is effective, relatively safe, and fast-acting option for patients with UC who have previously failed an anti-TNF agent, he said.

Challenges remain, however.

“Despite this exciting new therapeutic, there is still significant research needed to break our current therapeutic efficacy ceiling and get more IBD patients into a stable and durable remission,” Dr. Berinstein said. “Additional research is needed to develop personalized treatment strategies to address the unique needs of individual patients and to guide optimal medical management.”

Dr. Berinstein and his team are exploring the use of upadacitinib on the sickest IBD patients, “those admitted to the hospital with acute severe ulcerative colitis,” he said. Emerging data from multiple academic centers suggest that “upadacitinib induction may be a viable treatment strategy for these very high-risk patients. Of course, large prospective trials will be needed to confirm this,” he added.

The study was funded by AbbVie, which markets upadacitinib (Rinvoq). Lead author Dr. Loftus and several study authors disclosed financial relationships with AbbVie and other companies. Dr. Sakuraba and Dr. Berinstein reported having no relevant financial conflicts.

New more aggressive targets for blood pressure and lipids are among the changes to the annual American Diabetes Association (ADA) Standards of Care in Diabetes – 2023.

The document, long considered the gold standard for care of the more than 100 million Americans living with diabetes and prediabetes, was published as a supplement in Diabetes Care. The guidelines are also accessible to doctors via an app; last year’s standards were accessed more than 4 million times.

The standards now advise a blood pressure target for people with diabetes of less than 130/80 mm Hg, and low-density lipoprotein (LDL) cholesterol targets of below 70 mg/dL or no greater than 55 mg/dL, depending on the individual’s cardiovascular risk.

Courtesy Joslin Diabetes Center

“In this year’s version of the ADA Standards of Care – the longstanding guidelines for diabetes management globally – you’ll see information that really speaks to how we can more aggressively treat diabetes and reduce complications in a variety of different ways,” ADA Chief Scientific and Medical Officer Robert A. Gabbay, MD, PhD, said in an interview.

Other changes for 2023 include a new emphasis on weight loss as a goal of therapy for type 2 diabetes; guidance for screening and assessing peripheral arterial disease in an effort to prevent amputations; use of finerenone in people with diabetes and chronic kidney disease; use of approved point-of-care A1c tests; and guidance on screening for food insecurity, along with an elevated role for community health workers.

“The management of type 2 diabetes is not just about glucose,” Dr. Gabbay emphasized, noting that the ADA Standards have increasingly focused on cardiorenal risk as well as weight management. “We need to think about all those things, not just one. We have better tools now that have been helpful in being able to move forward with this.”
 

New targets in cardiovascular disease and risk management

As it has been for the past 6 years, the section on cardiovascular disease and risk management is also endorsed by the American College of Cardiology.

The new definition of hypertension in people with diabetes is ≥ 130 mm Hg systolic or ≥ 80 mm Hg diastolic blood pressure, repeated on two measurements at different times. Among individuals with established cardiovascular disease, hypertension can be diagnosed with one measurement of ≥ 180/110 mm Hg.

The goal of treatment is now less than 130/80 mm Hg if it can be reached safely.

In 2012, easing of the systolic target to 140 mm Hg by the ADA caused some controversy.

But, as Dr. Gabbay explained: “The evidence wasn’t there 10 years ago. We stuck to the evidence at that time, although there was a belief that lower was better. Over the past decade, a number of studies have made it quite clear that there is benefit to a lower target. That’s why we staked out the ground on this.”

The new Standards of Care also has new lipid targets. For people with diabetes aged 40-75 years at increased cardiovascular risk, including those with one or more atherosclerotic risk factors, high-intensity statin therapy is recommended to reduce LDL cholesterol by 50% or more from baseline and to a target of less than 70 mg/dL, in contrast to the previous target of 100 mg/dL.  

To achieve that goal, the document advises to consider adding ezetimibe or a PCSK9 inhibitor to maximally tolerated statin therapy.

For people with diabetes aged 40-75 who have established cardiovascular disease, treatment with high-intensity statin therapy is recommended with the target of a 50% or greater reduction from baseline and an LDL cholesterol level of 55 mg/dL or lower, in contrast to the previous 70 mg/dL.

“That is a lower goal than previously recommended, and based on strong evidence in the literature,” Dr. Gabbay noted.

Here, a stronger recommendation is made for ezetimibe or a PCSK9 inhibitor added to maximal statins.

And for people with diabetes older than 75 years, those already on statins should continue taking them. For those who aren’t, it may be reasonable to initiate moderate-intensity statin therapy after discussion of the benefits and risks.

Another new recommendation based on recent trial data is use of a sodium–glucose cotransporter 2 (SGLT2) inhibitor in people with diabetes and heart failure with preserved, as well as reduced, ejection fraction.
 

Kidney disease guidance updated: SGLT2 inhibitors, finerenone

Another recommendation calls for the addition of finerenone for people with type 2 diabetes who have chronic kidney disease (CKD) with albuminuria and have been treated with the maximum tolerated doses of an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) to improve cardiovascular outcomes as well as reduce the risk of CKD progression.

The threshold for initiating an SGLT2 inhibitor for kidney protection has changed to an estimated glomerular filtration rate (eGFR) ≥ 20 mL/min/1.73 m² and urinary albumin ≥ 200 mg/g creatinine (previously ≥ 25 mL/min/1.73 m² and ≥ 300 mg/g, respectively). An SGLT2 inhibitor may also be beneficial in people with a urinary albumin of normal to ≥ 200 mg/g creatinine, but supporting data have not yet been published.

Referral to a nephrologist is advised for individuals with increasing urinary albumin levels or continued decreasing eGFR or eGFR < 30 mL/min/1.73 m².
 

Weight loss, point-of-care testing, food insecurity assessment 

Other changes for 2023 include fresh emphasis on supporting weight loss of up to 15% with the new twincretin tirzepatide (Mounjaro) – approved in the United States in May for type 2 diabetes – added as a glucose-lowering drug with weight loss potential.

A novel section was added with guidance for peripheral arterial disease screening.

And a new recommendation advises use of point-of-care A1c testing for diabetes screening and diagnosis using only tests approved by the Food and Drug Administration.

Also introduced for 2023 is guidance to use community health workers to support the management of diabetes and cardiovascular risk factors, particularly in underserved areas and health systems.

“Community health workers can be a link to help people navigate and engage with the health system for better outcomes,” said Dr. Gabbay.

He added that these professionals are among those who can also assist with screening for food insecurity, another new recommendation. “We talk about screening for food insecurity and tools to use. That shouldn’t be something only dietitians do.”

Dr. Gabbay said he’d like to see more clinicians partner with community health workers. “We’d like to see more of that ... They should be considered part of the health care team,” he said.

Dr. Gabbay has reported serving on advisory boards for Lark, Health Reveal, Sweetch, StartUp Health, Vida Health, and Onduo.

A version of this article first appeared on Medscape.com.

New more aggressive targets for blood pressure and lipids are among the changes to the annual American Diabetes Association (ADA) Standards of Care in Diabetes – 2023.

The document, long considered the gold standard for care of the more than 100 million Americans living with diabetes and prediabetes, was published as a supplement in Diabetes Care. The guidelines are also accessible to doctors via an app; last year’s standards were accessed more than 4 million times.

The standards now advise a blood pressure target for people with diabetes of less than 130/80 mm Hg, and low-density lipoprotein (LDL) cholesterol targets of below 70 mg/dL or no greater than 55 mg/dL, depending on the individual’s cardiovascular risk.

Courtesy Joslin Diabetes Center

“In this year’s version of the ADA Standards of Care – the longstanding guidelines for diabetes management globally – you’ll see information that really speaks to how we can more aggressively treat diabetes and reduce complications in a variety of different ways,” ADA Chief Scientific and Medical Officer Robert A. Gabbay, MD, PhD, said in an interview.

Other changes for 2023 include a new emphasis on weight loss as a goal of therapy for type 2 diabetes; guidance for screening and assessing peripheral arterial disease in an effort to prevent amputations; use of finerenone in people with diabetes and chronic kidney disease; use of approved point-of-care A1c tests; and guidance on screening for food insecurity, along with an elevated role for community health workers.

“The management of type 2 diabetes is not just about glucose,” Dr. Gabbay emphasized, noting that the ADA Standards have increasingly focused on cardiorenal risk as well as weight management. “We need to think about all those things, not just one. We have better tools now that have been helpful in being able to move forward with this.”
 

New targets in cardiovascular disease and risk management

As it has been for the past 6 years, the section on cardiovascular disease and risk management is also endorsed by the American College of Cardiology.

The new definition of hypertension in people with diabetes is ≥ 130 mm Hg systolic or ≥ 80 mm Hg diastolic blood pressure, repeated on two measurements at different times. Among individuals with established cardiovascular disease, hypertension can be diagnosed with one measurement of ≥ 180/110 mm Hg.

The goal of treatment is now less than 130/80 mm Hg if it can be reached safely.

In 2012, easing of the systolic target to 140 mm Hg by the ADA caused some controversy.

But, as Dr. Gabbay explained: “The evidence wasn’t there 10 years ago. We stuck to the evidence at that time, although there was a belief that lower was better. Over the past decade, a number of studies have made it quite clear that there is benefit to a lower target. That’s why we staked out the ground on this.”

The new Standards of Care also has new lipid targets. For people with diabetes aged 40-75 years at increased cardiovascular risk, including those with one or more atherosclerotic risk factors, high-intensity statin therapy is recommended to reduce LDL cholesterol by 50% or more from baseline and to a target of less than 70 mg/dL, in contrast to the previous target of 100 mg/dL.  

To achieve that goal, the document advises to consider adding ezetimibe or a PCSK9 inhibitor to maximally tolerated statin therapy.

For people with diabetes aged 40-75 who have established cardiovascular disease, treatment with high-intensity statin therapy is recommended with the target of a 50% or greater reduction from baseline and an LDL cholesterol level of 55 mg/dL or lower, in contrast to the previous 70 mg/dL.

“That is a lower goal than previously recommended, and based on strong evidence in the literature,” Dr. Gabbay noted.

Here, a stronger recommendation is made for ezetimibe or a PCSK9 inhibitor added to maximal statins.

And for people with diabetes older than 75 years, those already on statins should continue taking them. For those who aren’t, it may be reasonable to initiate moderate-intensity statin therapy after discussion of the benefits and risks.

Another new recommendation based on recent trial data is use of a sodium–glucose cotransporter 2 (SGLT2) inhibitor in people with diabetes and heart failure with preserved, as well as reduced, ejection fraction.
 

Kidney disease guidance updated: SGLT2 inhibitors, finerenone

Another recommendation calls for the addition of finerenone for people with type 2 diabetes who have chronic kidney disease (CKD) with albuminuria and have been treated with the maximum tolerated doses of an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) to improve cardiovascular outcomes as well as reduce the risk of CKD progression.

The threshold for initiating an SGLT2 inhibitor for kidney protection has changed to an estimated glomerular filtration rate (eGFR) ≥ 20 mL/min/1.73 m² and urinary albumin ≥ 200 mg/g creatinine (previously ≥ 25 mL/min/1.73 m² and ≥ 300 mg/g, respectively). An SGLT2 inhibitor may also be beneficial in people with a urinary albumin of normal to ≥ 200 mg/g creatinine, but supporting data have not yet been published.

Referral to a nephrologist is advised for individuals with increasing urinary albumin levels or continued decreasing eGFR or eGFR < 30 mL/min/1.73 m².
 

Weight loss, point-of-care testing, food insecurity assessment 

Other changes for 2023 include fresh emphasis on supporting weight loss of up to 15% with the new twincretin tirzepatide (Mounjaro) – approved in the United States in May for type 2 diabetes – added as a glucose-lowering drug with weight loss potential.

A novel section was added with guidance for peripheral arterial disease screening.

And a new recommendation advises use of point-of-care A1c testing for diabetes screening and diagnosis using only tests approved by the Food and Drug Administration.

Also introduced for 2023 is guidance to use community health workers to support the management of diabetes and cardiovascular risk factors, particularly in underserved areas and health systems.

“Community health workers can be a link to help people navigate and engage with the health system for better outcomes,” said Dr. Gabbay.

He added that these professionals are among those who can also assist with screening for food insecurity, another new recommendation. “We talk about screening for food insecurity and tools to use. That shouldn’t be something only dietitians do.”

Dr. Gabbay said he’d like to see more clinicians partner with community health workers. “We’d like to see more of that ... They should be considered part of the health care team,” he said.

Dr. Gabbay has reported serving on advisory boards for Lark, Health Reveal, Sweetch, StartUp Health, Vida Health, and Onduo.

A version of this article first appeared on Medscape.com.

New more aggressive targets for blood pressure and lipids are among the changes to the annual American Diabetes Association (ADA) Standards of Care in Diabetes – 2023.

The document, long considered the gold standard for care of the more than 100 million Americans living with diabetes and prediabetes, was published as a supplement in Diabetes Care. The guidelines are also accessible to doctors via an app; last year’s standards were accessed more than 4 million times.

The standards now advise a blood pressure target for people with diabetes of less than 130/80 mm Hg, and low-density lipoprotein (LDL) cholesterol targets of below 70 mg/dL or no greater than 55 mg/dL, depending on the individual’s cardiovascular risk.

Courtesy Joslin Diabetes Center

“In this year’s version of the ADA Standards of Care – the longstanding guidelines for diabetes management globally – you’ll see information that really speaks to how we can more aggressively treat diabetes and reduce complications in a variety of different ways,” ADA Chief Scientific and Medical Officer Robert A. Gabbay, MD, PhD, said in an interview.

Other changes for 2023 include a new emphasis on weight loss as a goal of therapy for type 2 diabetes; guidance for screening and assessing peripheral arterial disease in an effort to prevent amputations; use of finerenone in people with diabetes and chronic kidney disease; use of approved point-of-care A1c tests; and guidance on screening for food insecurity, along with an elevated role for community health workers.

“The management of type 2 diabetes is not just about glucose,” Dr. Gabbay emphasized, noting that the ADA Standards have increasingly focused on cardiorenal risk as well as weight management. “We need to think about all those things, not just one. We have better tools now that have been helpful in being able to move forward with this.”
 

New targets in cardiovascular disease and risk management

As it has been for the past 6 years, the section on cardiovascular disease and risk management is also endorsed by the American College of Cardiology.

The new definition of hypertension in people with diabetes is ≥ 130 mm Hg systolic or ≥ 80 mm Hg diastolic blood pressure, repeated on two measurements at different times. Among individuals with established cardiovascular disease, hypertension can be diagnosed with one measurement of ≥ 180/110 mm Hg.

The goal of treatment is now less than 130/80 mm Hg if it can be reached safely.

In 2012, easing of the systolic target to 140 mm Hg by the ADA caused some controversy.

But, as Dr. Gabbay explained: “The evidence wasn’t there 10 years ago. We stuck to the evidence at that time, although there was a belief that lower was better. Over the past decade, a number of studies have made it quite clear that there is benefit to a lower target. That’s why we staked out the ground on this.”

The new Standards of Care also has new lipid targets. For people with diabetes aged 40-75 years at increased cardiovascular risk, including those with one or more atherosclerotic risk factors, high-intensity statin therapy is recommended to reduce LDL cholesterol by 50% or more from baseline and to a target of less than 70 mg/dL, in contrast to the previous target of 100 mg/dL.  

To achieve that goal, the document advises to consider adding ezetimibe or a PCSK9 inhibitor to maximally tolerated statin therapy.

For people with diabetes aged 40-75 who have established cardiovascular disease, treatment with high-intensity statin therapy is recommended with the target of a 50% or greater reduction from baseline and an LDL cholesterol level of 55 mg/dL or lower, in contrast to the previous 70 mg/dL.

“That is a lower goal than previously recommended, and based on strong evidence in the literature,” Dr. Gabbay noted.

Here, a stronger recommendation is made for ezetimibe or a PCSK9 inhibitor added to maximal statins.

And for people with diabetes older than 75 years, those already on statins should continue taking them. For those who aren’t, it may be reasonable to initiate moderate-intensity statin therapy after discussion of the benefits and risks.

Another new recommendation based on recent trial data is use of a sodium–glucose cotransporter 2 (SGLT2) inhibitor in people with diabetes and heart failure with preserved, as well as reduced, ejection fraction.
 

Kidney disease guidance updated: SGLT2 inhibitors, finerenone

Another recommendation calls for the addition of finerenone for people with type 2 diabetes who have chronic kidney disease (CKD) with albuminuria and have been treated with the maximum tolerated doses of an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) to improve cardiovascular outcomes as well as reduce the risk of CKD progression.

The threshold for initiating an SGLT2 inhibitor for kidney protection has changed to an estimated glomerular filtration rate (eGFR) ≥ 20 mL/min/1.73 m² and urinary albumin ≥ 200 mg/g creatinine (previously ≥ 25 mL/min/1.73 m² and ≥ 300 mg/g, respectively). An SGLT2 inhibitor may also be beneficial in people with a urinary albumin of normal to ≥ 200 mg/g creatinine, but supporting data have not yet been published.

Referral to a nephrologist is advised for individuals with increasing urinary albumin levels or continued decreasing eGFR or eGFR < 30 mL/min/1.73 m².
 

Weight loss, point-of-care testing, food insecurity assessment 

Other changes for 2023 include fresh emphasis on supporting weight loss of up to 15% with the new twincretin tirzepatide (Mounjaro) – approved in the United States in May for type 2 diabetes – added as a glucose-lowering drug with weight loss potential.

A novel section was added with guidance for peripheral arterial disease screening.

And a new recommendation advises use of point-of-care A1c testing for diabetes screening and diagnosis using only tests approved by the Food and Drug Administration.

Also introduced for 2023 is guidance to use community health workers to support the management of diabetes and cardiovascular risk factors, particularly in underserved areas and health systems.

“Community health workers can be a link to help people navigate and engage with the health system for better outcomes,” said Dr. Gabbay.

He added that these professionals are among those who can also assist with screening for food insecurity, another new recommendation. “We talk about screening for food insecurity and tools to use. That shouldn’t be something only dietitians do.”

Dr. Gabbay said he’d like to see more clinicians partner with community health workers. “We’d like to see more of that ... They should be considered part of the health care team,” he said.

Dr. Gabbay has reported serving on advisory boards for Lark, Health Reveal, Sweetch, StartUp Health, Vida Health, and Onduo.

A version of this article first appeared on Medscape.com.

It was the last monoclonal antibody treatment standing. But less than 10 months after the U.S. Food and Drug Administration gave bebtelovimab its emergency use authorization (EUA) to fight COVID-19, it earlier this month de-authorized it, just as it had for other monoclonal antibody treatments, and for the same reason: The treatments were outwitted by the viral mutations.
 

Bebtelovimab couldn’t neutralize the Omicron subvariants BQ.1 and BQ.1.1, the cause of nearly 60% of COVID cases nationally as of November 30.

Next on the chopping block, some predict, will be Evusheld, the combination of tixagevimab and cilgavimab given as a preventive monoclonal antibody to people who are immunocompromised and at high risk of contracting COVID and to those who can’t take the vaccine. In October, the FDA warned that Evusheld was not neutralizing circulating COVID variants.

As the options for treating and preventing COVID decline, will companies rally quickly to develop new ones, or cut their losses in developing treatments that may work for only a few months, given the speed of viral mutations?

But although monoclonal antibody treatments are off the table, at least for now, antiviral drugs – including Paxlovid – are still very much available, and some say underused.

Others suggest it’s time to resurrect interest in convalescent plasma, a treatment used early in the pandemic before drugs or vaccines were here and still authorized for use in those who are immunosuppressed or receiving immunosuppressive treatment.

And on the prevention front, staying up to date with booster vaccines, masking, and taking other precautions should be stressed more, others say, regardless of the number of treatment options, and especially now, as cases rise and people gather for the winter holidays.
 

‘A major setback’

The bebtelovimab de-authorization was “a major setback,” but an understandable one, said Arturo Casadevall, MD, PhD, professor and chair of molecular microbiology and immunology at the Johns Hopkins Bloomberg School of Public Health in Baltimore. “Monoclonal antibodies are great drugs. We are in an unfortunate situation in that they are vulnerable to changes in the virus” and can’t offer long-lasting protection.

Supplies of bebtelovimab will be retained, according to the FDA, in case variants susceptible to it return.

“What happened to bebtelovimab is no surprise,” agreed Amesh Adalja, MD, senior scholar at Johns Hopkins Center for Health Security. “This is what is going to happen when you are targeting a virus that mutates a lot.”

Monoclonal antibodies work by binding to the spike protein on the virus surface to prevent it from entering cells.

However, Dr. Adalja doesn’t view the disappearance of monoclonal antibody treatments as a major setback. Monoclonal antibodies were not the primary way COVID was treated, he said.

While he does believe it’s important that more monoclonal antibody treatments be developed, “I think it’s important to remember we still have Paxlovid while everyone is lamenting the loss of bebtelovimab.’’
 

Antivirals: What’s here, what’s coming

Compared with monoclonal antibodies, “Paxlovid remains a much easier drug to give,” Dr. Adalja told this news organization, because it is taken orally, not intravenously.

And it’s effective. In a recent study, researchers found that adults diagnosed with COVID given Paxlovid within 5 days of diagnosis had a 51% lower hospitalization rate within the next 30 days than those not given it. Another study shows it could also reduce a person’s risk of developing long COVID by 26%.

Paxlovid is underused, Dr. Adalja said, partly because the rebound potential got more press than the effectiveness. When a celebrity got rebound from Paxlovid, he said, that would make the news, overshadowing the research on its effectiveness.

Besides Paxlovid, the antivirals remdesivir (Veklury), given intravenously for 3 days, and molnupiravir (Lagevrio), taken orally, are also still available. Antivirals work by targeting specific parts of the virus to prevent it from multiplying.

In the lab, remdesivir, molnupiravir, and another antiviral, nirmatrelvir, all appear to be effective against both BQ.1.1 (a BA.5 subvariant) and XBB (a BA.2 subvariant), both rapidly rising in the United States, according to a report last week in the New England Journal of Medicine.

The researchers also tested several monoclonal antibodies and found they did not neutralize either of the subvariants BQ.1.1 and XBB.

A new oral antiviral, Xocova (ensitrelvir fumaric acid), from Japanese manufacturer Shionogi, received emergency approval in Japan on November 22. It’s taken once a day for 5 days. The goal is to expand access to it globally, according to the company.

Pardes Biosciences launched a phase 2 trial in September for its oral antiviral drug (PBI-0451), under study as a treatment and preventive for COVID. It expects data by the first quarter of 2023.

Pfizer, which makes Paxlovid, has partnered with Clear Creek Bio to develop another oral antiviral COVID drug.
 

Other approaches

A receptor protein known as ACE2 (angiotensin-converting enzyme 2) is the main “doorway” that SARS-CoV-2 uses to enter and infect cells.

Dana-Farber Cancer Institute scientists are developing a “decoy” drug that works by mimicking the ACE2 receptor on the surface of cells; when the virus tries to bind to it, the spike protein is destroyed. Human trials have not yet started.

Other researchers are investigating whether an already-approved drug used to treat a liver disease, Actigall (UDCA/ursodeoxycholic acid), could protect against COVID infection by reducing ACE2.

So far, the researchers have found in early research that people taking UDCA for liver conditions were less likely than those not taking the drug to have severe COVID. They also found that UDCA reduced SARS-CoV-2 infection in human lungs maintained outside the body.
 

Monoclonal antibody treatments?

After the FDA decision to withdraw the bebtelovimab EUA, which Eli Lilly said it agreed with, the company issued a statement, promising it wasn’t giving up on monoclonal antibody treatments.

“Lilly will continue to search and evaluate monoclonal antibodies to identify potential candidates for clinical development against new variants,” it read in part.

AstraZeneca, which makes Evusheld, is also continuing to work on monoclonal antibody development. According to a spokesperson, “We are also developing a new long-acting antibody combination – AZD5156 – which has been shown in the lab to neutralize emerging new variants and all known variants to date. We are working to accelerate the development of AZD5156 to make it available at the end of 2023.”

The AstraZeneca spokesperson said he could share no more information about what the combination would include.
 

A convalescent plasma comeback?

Although Paxlovid can help, there are many contraindications to it, such as drug-drug interactions, Dr. Casadevall told this news organization. And now that the monoclonal antibody treatments have been paused, convalescent plasma “is the only antibody-based therapy that is reliably available. Convalescent plasma includes thousands of different antibodies.”

With his colleagues, Dr. Casadevall evaluated plasma samples from 740 patients. Some had received booster vaccines and been infected with Omicron, others had received boosters and not been infected, and still others had not been vaccinated and became infected.

In a report (not yet peer-reviewed), they found the plasma from those who had been infected or boosted within the past 6 months neutralized the new Omicron variants BQ.1.1, XBB.1, and BF.7.
 

A push for boosters, masks

To get through the coming months, taking precautions like masking and distancing and staying up to date on booster vaccinations, especially for older adults, can make a difference, other experts say.

In a Twitter thread in early December, Peter Hotez, MD, PhD, professor of pediatrics and molecular virology and microbiology at Baylor College of Medicine, Houston, urged people to take COVID seriously as holiday parties and gatherings occur.

“The single most impactful thing you can do is get your bivalent booster,” he tweeted, as well as give your kids the booster, citing preliminary research that the bivalent mRNA booster broadens immunity against the Omicron subvariants.

For seniors, he said, ‘‘if you get breakthrough COVID, [it’s] really important to get Paxlovid.” Masks will help not only for COVID but also influenza, respiratory syncytial virus (RSV), and other conditions.

Mitigation measures have largely been abandoned, according to Eric Topol, MD, director of the Scripps Research Translational Institute, La Jolla, Calif., and editor-in-chief of Medscape. In an op-ed in the Los Angeles Times, and on his Twitter feed, he reminds people about masking and urges people to get the bivalent booster.

According to the Centers for Disease Control and Prevention, as of Dec. 8, only 13.5% of people aged 5 and older have gotten an updated booster, despite research that shows an increase in antibodies to BQ.1.1. Recent research has found that the bivalent booster increases antibodies to BQ.1.1 by up to 10-fold, Dr. Topol said.

Dr. Adalja is on advisory boards for Shionogi, GSK, and Pardes. Dr. Casadevall reports no relevant financial relationships.

A version of this article first appeared on Medscape.com.

It was the last monoclonal antibody treatment standing. But less than 10 months after the U.S. Food and Drug Administration gave bebtelovimab its emergency use authorization (EUA) to fight COVID-19, it earlier this month de-authorized it, just as it had for other monoclonal antibody treatments, and for the same reason: The treatments were outwitted by the viral mutations.
 

Bebtelovimab couldn’t neutralize the Omicron subvariants BQ.1 and BQ.1.1, the cause of nearly 60% of COVID cases nationally as of November 30.

Next on the chopping block, some predict, will be Evusheld, the combination of tixagevimab and cilgavimab given as a preventive monoclonal antibody to people who are immunocompromised and at high risk of contracting COVID and to those who can’t take the vaccine. In October, the FDA warned that Evusheld was not neutralizing circulating COVID variants.

As the options for treating and preventing COVID decline, will companies rally quickly to develop new ones, or cut their losses in developing treatments that may work for only a few months, given the speed of viral mutations?

But although monoclonal antibody treatments are off the table, at least for now, antiviral drugs – including Paxlovid – are still very much available, and some say underused.

Others suggest it’s time to resurrect interest in convalescent plasma, a treatment used early in the pandemic before drugs or vaccines were here and still authorized for use in those who are immunosuppressed or receiving immunosuppressive treatment.

And on the prevention front, staying up to date with booster vaccines, masking, and taking other precautions should be stressed more, others say, regardless of the number of treatment options, and especially now, as cases rise and people gather for the winter holidays.
 

‘A major setback’

The bebtelovimab de-authorization was “a major setback,” but an understandable one, said Arturo Casadevall, MD, PhD, professor and chair of molecular microbiology and immunology at the Johns Hopkins Bloomberg School of Public Health in Baltimore. “Monoclonal antibodies are great drugs. We are in an unfortunate situation in that they are vulnerable to changes in the virus” and can’t offer long-lasting protection.

Supplies of bebtelovimab will be retained, according to the FDA, in case variants susceptible to it return.

“What happened to bebtelovimab is no surprise,” agreed Amesh Adalja, MD, senior scholar at Johns Hopkins Center for Health Security. “This is what is going to happen when you are targeting a virus that mutates a lot.”

Monoclonal antibodies work by binding to the spike protein on the virus surface to prevent it from entering cells.

However, Dr. Adalja doesn’t view the disappearance of monoclonal antibody treatments as a major setback. Monoclonal antibodies were not the primary way COVID was treated, he said.

While he does believe it’s important that more monoclonal antibody treatments be developed, “I think it’s important to remember we still have Paxlovid while everyone is lamenting the loss of bebtelovimab.’’
 

Antivirals: What’s here, what’s coming

Compared with monoclonal antibodies, “Paxlovid remains a much easier drug to give,” Dr. Adalja told this news organization, because it is taken orally, not intravenously.

And it’s effective. In a recent study, researchers found that adults diagnosed with COVID given Paxlovid within 5 days of diagnosis had a 51% lower hospitalization rate within the next 30 days than those not given it. Another study shows it could also reduce a person’s risk of developing long COVID by 26%.

Paxlovid is underused, Dr. Adalja said, partly because the rebound potential got more press than the effectiveness. When a celebrity got rebound from Paxlovid, he said, that would make the news, overshadowing the research on its effectiveness.

Besides Paxlovid, the antivirals remdesivir (Veklury), given intravenously for 3 days, and molnupiravir (Lagevrio), taken orally, are also still available. Antivirals work by targeting specific parts of the virus to prevent it from multiplying.

In the lab, remdesivir, molnupiravir, and another antiviral, nirmatrelvir, all appear to be effective against both BQ.1.1 (a BA.5 subvariant) and XBB (a BA.2 subvariant), both rapidly rising in the United States, according to a report last week in the New England Journal of Medicine.

The researchers also tested several monoclonal antibodies and found they did not neutralize either of the subvariants BQ.1.1 and XBB.

A new oral antiviral, Xocova (ensitrelvir fumaric acid), from Japanese manufacturer Shionogi, received emergency approval in Japan on November 22. It’s taken once a day for 5 days. The goal is to expand access to it globally, according to the company.

Pardes Biosciences launched a phase 2 trial in September for its oral antiviral drug (PBI-0451), under study as a treatment and preventive for COVID. It expects data by the first quarter of 2023.

Pfizer, which makes Paxlovid, has partnered with Clear Creek Bio to develop another oral antiviral COVID drug.
 

Other approaches

A receptor protein known as ACE2 (angiotensin-converting enzyme 2) is the main “doorway” that SARS-CoV-2 uses to enter and infect cells.

Dana-Farber Cancer Institute scientists are developing a “decoy” drug that works by mimicking the ACE2 receptor on the surface of cells; when the virus tries to bind to it, the spike protein is destroyed. Human trials have not yet started.

Other researchers are investigating whether an already-approved drug used to treat a liver disease, Actigall (UDCA/ursodeoxycholic acid), could protect against COVID infection by reducing ACE2.

So far, the researchers have found in early research that people taking UDCA for liver conditions were less likely than those not taking the drug to have severe COVID. They also found that UDCA reduced SARS-CoV-2 infection in human lungs maintained outside the body.
 

Monoclonal antibody treatments?

After the FDA decision to withdraw the bebtelovimab EUA, which Eli Lilly said it agreed with, the company issued a statement, promising it wasn’t giving up on monoclonal antibody treatments.

“Lilly will continue to search and evaluate monoclonal antibodies to identify potential candidates for clinical development against new variants,” it read in part.

AstraZeneca, which makes Evusheld, is also continuing to work on monoclonal antibody development. According to a spokesperson, “We are also developing a new long-acting antibody combination – AZD5156 – which has been shown in the lab to neutralize emerging new variants and all known variants to date. We are working to accelerate the development of AZD5156 to make it available at the end of 2023.”

The AstraZeneca spokesperson said he could share no more information about what the combination would include.
 

A convalescent plasma comeback?

Although Paxlovid can help, there are many contraindications to it, such as drug-drug interactions, Dr. Casadevall told this news organization. And now that the monoclonal antibody treatments have been paused, convalescent plasma “is the only antibody-based therapy that is reliably available. Convalescent plasma includes thousands of different antibodies.”

With his colleagues, Dr. Casadevall evaluated plasma samples from 740 patients. Some had received booster vaccines and been infected with Omicron, others had received boosters and not been infected, and still others had not been vaccinated and became infected.

In a report (not yet peer-reviewed), they found the plasma from those who had been infected or boosted within the past 6 months neutralized the new Omicron variants BQ.1.1, XBB.1, and BF.7.
 

A push for boosters, masks

To get through the coming months, taking precautions like masking and distancing and staying up to date on booster vaccinations, especially for older adults, can make a difference, other experts say.

In a Twitter thread in early December, Peter Hotez, MD, PhD, professor of pediatrics and molecular virology and microbiology at Baylor College of Medicine, Houston, urged people to take COVID seriously as holiday parties and gatherings occur.

“The single most impactful thing you can do is get your bivalent booster,” he tweeted, as well as give your kids the booster, citing preliminary research that the bivalent mRNA booster broadens immunity against the Omicron subvariants.

For seniors, he said, ‘‘if you get breakthrough COVID, [it’s] really important to get Paxlovid.” Masks will help not only for COVID but also influenza, respiratory syncytial virus (RSV), and other conditions.

Mitigation measures have largely been abandoned, according to Eric Topol, MD, director of the Scripps Research Translational Institute, La Jolla, Calif., and editor-in-chief of Medscape. In an op-ed in the Los Angeles Times, and on his Twitter feed, he reminds people about masking and urges people to get the bivalent booster.

According to the Centers for Disease Control and Prevention, as of Dec. 8, only 13.5% of people aged 5 and older have gotten an updated booster, despite research that shows an increase in antibodies to BQ.1.1. Recent research has found that the bivalent booster increases antibodies to BQ.1.1 by up to 10-fold, Dr. Topol said.

Dr. Adalja is on advisory boards for Shionogi, GSK, and Pardes. Dr. Casadevall reports no relevant financial relationships.

A version of this article first appeared on Medscape.com.

It was the last monoclonal antibody treatment standing. But less than 10 months after the U.S. Food and Drug Administration gave bebtelovimab its emergency use authorization (EUA) to fight COVID-19, it earlier this month de-authorized it, just as it had for other monoclonal antibody treatments, and for the same reason: The treatments were outwitted by the viral mutations.
 

Bebtelovimab couldn’t neutralize the Omicron subvariants BQ.1 and BQ.1.1, the cause of nearly 60% of COVID cases nationally as of November 30.

Next on the chopping block, some predict, will be Evusheld, the combination of tixagevimab and cilgavimab given as a preventive monoclonal antibody to people who are immunocompromised and at high risk of contracting COVID and to those who can’t take the vaccine. In October, the FDA warned that Evusheld was not neutralizing circulating COVID variants.

As the options for treating and preventing COVID decline, will companies rally quickly to develop new ones, or cut their losses in developing treatments that may work for only a few months, given the speed of viral mutations?

But although monoclonal antibody treatments are off the table, at least for now, antiviral drugs – including Paxlovid – are still very much available, and some say underused.

Others suggest it’s time to resurrect interest in convalescent plasma, a treatment used early in the pandemic before drugs or vaccines were here and still authorized for use in those who are immunosuppressed or receiving immunosuppressive treatment.

And on the prevention front, staying up to date with booster vaccines, masking, and taking other precautions should be stressed more, others say, regardless of the number of treatment options, and especially now, as cases rise and people gather for the winter holidays.
 

‘A major setback’

The bebtelovimab de-authorization was “a major setback,” but an understandable one, said Arturo Casadevall, MD, PhD, professor and chair of molecular microbiology and immunology at the Johns Hopkins Bloomberg School of Public Health in Baltimore. “Monoclonal antibodies are great drugs. We are in an unfortunate situation in that they are vulnerable to changes in the virus” and can’t offer long-lasting protection.

Supplies of bebtelovimab will be retained, according to the FDA, in case variants susceptible to it return.

“What happened to bebtelovimab is no surprise,” agreed Amesh Adalja, MD, senior scholar at Johns Hopkins Center for Health Security. “This is what is going to happen when you are targeting a virus that mutates a lot.”

Monoclonal antibodies work by binding to the spike protein on the virus surface to prevent it from entering cells.

However, Dr. Adalja doesn’t view the disappearance of monoclonal antibody treatments as a major setback. Monoclonal antibodies were not the primary way COVID was treated, he said.

While he does believe it’s important that more monoclonal antibody treatments be developed, “I think it’s important to remember we still have Paxlovid while everyone is lamenting the loss of bebtelovimab.’’
 

Antivirals: What’s here, what’s coming

Compared with monoclonal antibodies, “Paxlovid remains a much easier drug to give,” Dr. Adalja told this news organization, because it is taken orally, not intravenously.

And it’s effective. In a recent study, researchers found that adults diagnosed with COVID given Paxlovid within 5 days of diagnosis had a 51% lower hospitalization rate within the next 30 days than those not given it. Another study shows it could also reduce a person’s risk of developing long COVID by 26%.

Paxlovid is underused, Dr. Adalja said, partly because the rebound potential got more press than the effectiveness. When a celebrity got rebound from Paxlovid, he said, that would make the news, overshadowing the research on its effectiveness.

Besides Paxlovid, the antivirals remdesivir (Veklury), given intravenously for 3 days, and molnupiravir (Lagevrio), taken orally, are also still available. Antivirals work by targeting specific parts of the virus to prevent it from multiplying.

In the lab, remdesivir, molnupiravir, and another antiviral, nirmatrelvir, all appear to be effective against both BQ.1.1 (a BA.5 subvariant) and XBB (a BA.2 subvariant), both rapidly rising in the United States, according to a report last week in the New England Journal of Medicine.

The researchers also tested several monoclonal antibodies and found they did not neutralize either of the subvariants BQ.1.1 and XBB.

A new oral antiviral, Xocova (ensitrelvir fumaric acid), from Japanese manufacturer Shionogi, received emergency approval in Japan on November 22. It’s taken once a day for 5 days. The goal is to expand access to it globally, according to the company.

Pardes Biosciences launched a phase 2 trial in September for its oral antiviral drug (PBI-0451), under study as a treatment and preventive for COVID. It expects data by the first quarter of 2023.

Pfizer, which makes Paxlovid, has partnered with Clear Creek Bio to develop another oral antiviral COVID drug.
 

Other approaches

A receptor protein known as ACE2 (angiotensin-converting enzyme 2) is the main “doorway” that SARS-CoV-2 uses to enter and infect cells.

Dana-Farber Cancer Institute scientists are developing a “decoy” drug that works by mimicking the ACE2 receptor on the surface of cells; when the virus tries to bind to it, the spike protein is destroyed. Human trials have not yet started.

Other researchers are investigating whether an already-approved drug used to treat a liver disease, Actigall (UDCA/ursodeoxycholic acid), could protect against COVID infection by reducing ACE2.

So far, the researchers have found in early research that people taking UDCA for liver conditions were less likely than those not taking the drug to have severe COVID. They also found that UDCA reduced SARS-CoV-2 infection in human lungs maintained outside the body.
 

Monoclonal antibody treatments?

After the FDA decision to withdraw the bebtelovimab EUA, which Eli Lilly said it agreed with, the company issued a statement, promising it wasn’t giving up on monoclonal antibody treatments.

“Lilly will continue to search and evaluate monoclonal antibodies to identify potential candidates for clinical development against new variants,” it read in part.

AstraZeneca, which makes Evusheld, is also continuing to work on monoclonal antibody development. According to a spokesperson, “We are also developing a new long-acting antibody combination – AZD5156 – which has been shown in the lab to neutralize emerging new variants and all known variants to date. We are working to accelerate the development of AZD5156 to make it available at the end of 2023.”

The AstraZeneca spokesperson said he could share no more information about what the combination would include.
 

A convalescent plasma comeback?

Although Paxlovid can help, there are many contraindications to it, such as drug-drug interactions, Dr. Casadevall told this news organization. And now that the monoclonal antibody treatments have been paused, convalescent plasma “is the only antibody-based therapy that is reliably available. Convalescent plasma includes thousands of different antibodies.”

With his colleagues, Dr. Casadevall evaluated plasma samples from 740 patients. Some had received booster vaccines and been infected with Omicron, others had received boosters and not been infected, and still others had not been vaccinated and became infected.

In a report (not yet peer-reviewed), they found the plasma from those who had been infected or boosted within the past 6 months neutralized the new Omicron variants BQ.1.1, XBB.1, and BF.7.
 

A push for boosters, masks

To get through the coming months, taking precautions like masking and distancing and staying up to date on booster vaccinations, especially for older adults, can make a difference, other experts say.

In a Twitter thread in early December, Peter Hotez, MD, PhD, professor of pediatrics and molecular virology and microbiology at Baylor College of Medicine, Houston, urged people to take COVID seriously as holiday parties and gatherings occur.

“The single most impactful thing you can do is get your bivalent booster,” he tweeted, as well as give your kids the booster, citing preliminary research that the bivalent mRNA booster broadens immunity against the Omicron subvariants.

For seniors, he said, ‘‘if you get breakthrough COVID, [it’s] really important to get Paxlovid.” Masks will help not only for COVID but also influenza, respiratory syncytial virus (RSV), and other conditions.

Mitigation measures have largely been abandoned, according to Eric Topol, MD, director of the Scripps Research Translational Institute, La Jolla, Calif., and editor-in-chief of Medscape. In an op-ed in the Los Angeles Times, and on his Twitter feed, he reminds people about masking and urges people to get the bivalent booster.

According to the Centers for Disease Control and Prevention, as of Dec. 8, only 13.5% of people aged 5 and older have gotten an updated booster, despite research that shows an increase in antibodies to BQ.1.1. Recent research has found that the bivalent booster increases antibodies to BQ.1.1 by up to 10-fold, Dr. Topol said.

Dr. Adalja is on advisory boards for Shionogi, GSK, and Pardes. Dr. Casadevall reports no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The notion that the reason people with obesity are not losing weight is that they aren’t sufficiently incentivized to do so is toxic.
 

It denies the impact of the thousands of genes and dozens of hormones involved in our individual levels of hunger, cravings, and fullness. It denies the torrential current of our ultraprocessed and calorific food environment. It denies the constant push of food advertising and the role food has taken on as the star of even the smallest of events and celebrations. It denies the role of food as a seminal pleasure in a world that, even for those possessing great degrees of privilege is challenging, let alone for those facing tremendous and varied difficulties. And of course, it upholds the hateful notion that, if people just wanted it badly enough, they’d manage their weight, the corollary of which is that people with obesity are unmotivated and lazy. 

Yet the notion that, if people want it badly enough, they’d make it happen, is incredibly commonplace. It’s so commonplace that NBC aired their prime-time televised reality show The Biggest Loser from 2004 through 2016, featuring people with obesity competing for a $500,000 prize during a 30-week–long orgy of fat-shaming, victim-blaming, hugely restrictive eating, and injury. It’s also so commonplace that studies are still being conducted exploring the impact of paying people to lose weight.

The most recent of these – “Effectiveness of Goal-Directed and Outcome-Based Financial Incentives for Weight Loss in Primary Care Patients With Obesity Living in Socioeconomically Disadvantaged Neighborhoods: A Randomized Clinical Trial” – examined the effects of randomly assigning participants whose annual household incomes were less than $40,000 to either a free year of Weight Watchers and the provisions of basic weight loss advice (exercise, track your food, eat healthfully, et cetera) or to an incentivized program that would see them earning up to $750 over 6 months, with dollars being awarded for such things as attendance in education sessions, keeping a food diary, recording their weight, and obtaining a certain amount of exercise or for weight loss.

Resultswise – though you might not have gathered it from the conclusion of the paper, which states that incentives were more effective at 12 months – the average incentivized participant lost roughly 6 pounds more than those given only resources. It should also be mentioned that over half of the incentivized group did not complete the study.

That these sorts of studies are still being conducted is depressing. Medicine and academia need to actively stop promoting harmful stereotypes when it comes to the genesis of a chronic noncommunicable disease that is not caused by a lack of desire, needing the right incentive, but is rather caused by the interaction of millions of years of evolution during extreme dietary insecurity with a modern-day food environment and culture that constantly offers, provides, and encourages consumption. This is especially true now that there are effective antiobesity medications whose success underwrites the notion that it’s physiology, rather than a lack of wanting it enough, that gets in the way of sustained success.

A version of this article first appeared on Medscape.com.

The notion that the reason people with obesity are not losing weight is that they aren’t sufficiently incentivized to do so is toxic.
 

It denies the impact of the thousands of genes and dozens of hormones involved in our individual levels of hunger, cravings, and fullness. It denies the torrential current of our ultraprocessed and calorific food environment. It denies the constant push of food advertising and the role food has taken on as the star of even the smallest of events and celebrations. It denies the role of food as a seminal pleasure in a world that, even for those possessing great degrees of privilege is challenging, let alone for those facing tremendous and varied difficulties. And of course, it upholds the hateful notion that, if people just wanted it badly enough, they’d manage their weight, the corollary of which is that people with obesity are unmotivated and lazy. 

Yet the notion that, if people want it badly enough, they’d make it happen, is incredibly commonplace. It’s so commonplace that NBC aired their prime-time televised reality show The Biggest Loser from 2004 through 2016, featuring people with obesity competing for a $500,000 prize during a 30-week–long orgy of fat-shaming, victim-blaming, hugely restrictive eating, and injury. It’s also so commonplace that studies are still being conducted exploring the impact of paying people to lose weight.

The most recent of these – “Effectiveness of Goal-Directed and Outcome-Based Financial Incentives for Weight Loss in Primary Care Patients With Obesity Living in Socioeconomically Disadvantaged Neighborhoods: A Randomized Clinical Trial” – examined the effects of randomly assigning participants whose annual household incomes were less than $40,000 to either a free year of Weight Watchers and the provisions of basic weight loss advice (exercise, track your food, eat healthfully, et cetera) or to an incentivized program that would see them earning up to $750 over 6 months, with dollars being awarded for such things as attendance in education sessions, keeping a food diary, recording their weight, and obtaining a certain amount of exercise or for weight loss.

Resultswise – though you might not have gathered it from the conclusion of the paper, which states that incentives were more effective at 12 months – the average incentivized participant lost roughly 6 pounds more than those given only resources. It should also be mentioned that over half of the incentivized group did not complete the study.

That these sorts of studies are still being conducted is depressing. Medicine and academia need to actively stop promoting harmful stereotypes when it comes to the genesis of a chronic noncommunicable disease that is not caused by a lack of desire, needing the right incentive, but is rather caused by the interaction of millions of years of evolution during extreme dietary insecurity with a modern-day food environment and culture that constantly offers, provides, and encourages consumption. This is especially true now that there are effective antiobesity medications whose success underwrites the notion that it’s physiology, rather than a lack of wanting it enough, that gets in the way of sustained success.

A version of this article first appeared on Medscape.com.

The notion that the reason people with obesity are not losing weight is that they aren’t sufficiently incentivized to do so is toxic.
 

It denies the impact of the thousands of genes and dozens of hormones involved in our individual levels of hunger, cravings, and fullness. It denies the torrential current of our ultraprocessed and calorific food environment. It denies the constant push of food advertising and the role food has taken on as the star of even the smallest of events and celebrations. It denies the role of food as a seminal pleasure in a world that, even for those possessing great degrees of privilege is challenging, let alone for those facing tremendous and varied difficulties. And of course, it upholds the hateful notion that, if people just wanted it badly enough, they’d manage their weight, the corollary of which is that people with obesity are unmotivated and lazy. 

Yet the notion that, if people want it badly enough, they’d make it happen, is incredibly commonplace. It’s so commonplace that NBC aired their prime-time televised reality show The Biggest Loser from 2004 through 2016, featuring people with obesity competing for a $500,000 prize during a 30-week–long orgy of fat-shaming, victim-blaming, hugely restrictive eating, and injury. It’s also so commonplace that studies are still being conducted exploring the impact of paying people to lose weight.

The most recent of these – “Effectiveness of Goal-Directed and Outcome-Based Financial Incentives for Weight Loss in Primary Care Patients With Obesity Living in Socioeconomically Disadvantaged Neighborhoods: A Randomized Clinical Trial” – examined the effects of randomly assigning participants whose annual household incomes were less than $40,000 to either a free year of Weight Watchers and the provisions of basic weight loss advice (exercise, track your food, eat healthfully, et cetera) or to an incentivized program that would see them earning up to $750 over 6 months, with dollars being awarded for such things as attendance in education sessions, keeping a food diary, recording their weight, and obtaining a certain amount of exercise or for weight loss.

Resultswise – though you might not have gathered it from the conclusion of the paper, which states that incentives were more effective at 12 months – the average incentivized participant lost roughly 6 pounds more than those given only resources. It should also be mentioned that over half of the incentivized group did not complete the study.

That these sorts of studies are still being conducted is depressing. Medicine and academia need to actively stop promoting harmful stereotypes when it comes to the genesis of a chronic noncommunicable disease that is not caused by a lack of desire, needing the right incentive, but is rather caused by the interaction of millions of years of evolution during extreme dietary insecurity with a modern-day food environment and culture that constantly offers, provides, and encourages consumption. This is especially true now that there are effective antiobesity medications whose success underwrites the notion that it’s physiology, rather than a lack of wanting it enough, that gets in the way of sustained success.

A version of this article first appeared on Medscape.com.

Eating a low-carbohydrate, high-fat (LCHF) diet, instead of a high-carbohydrate, low-fat diet (HCLF), leads to significant improvements in type 2 diabetes (T2D), a new study finds.

This was true regardless of an individual’s calorie intake, in the randomized controlled trial published in the Annals of Internal Medicine.

Patients with T2D who ate a low-carb, high-fat diet (LCHF) lost more weight and saw greater improvements in both glycemic control and insulin resistance than those who ate a high-carb, low-fat diet (HCLF), reported lead author Camilla Dalby Hansen, MD, of University of Southern Denmark, Odense, and colleagues, suggesting that this is an effective, nonpharmaceutical treatment option for T2D.

The trial enrolled 185 patients with T2D, for whom low-calorie diets are often recommended to induce weight loss and improve glycemic control.

The trouble with this common recommendation, the investigators wrote, is that it induces hunger, so few patients stick to it.

“Therefore, calorie-unrestricted diets may be a better alternative to achieve long-term maintenance,” Dr. Hansen and colleagues wrote, noting that this approach “is not widely investigated.”
 

Study methods and results

In the new study, participants were randomized in a 2:1 ratio to follow the LCHF or HCLF diet for 6 months, with no restriction on calorie intake. Patients were evaluated at baseline, 3 months, 6 months, and 9 months (3 months after discontinuation). Parameters included glycemic control, serum lipid levels, and metabolic markers. The final analysis included 165 patients.

While patients in both groups lost weight, those in the LCHF group lost, on average, about 8 pounds more than the HCLF group, a significant difference. While the LCHF diet was associated with greater improvements in glycemic control (HbA1c) than the HCLF diet, it also led to slightly greater increases in LDL levels. In both groups, HDL levels increased, and triglycerides decreased, without significant differences between groups.

The above changes were not sustained 3 months after finishing the diet.

“I believe we have sufficient data to include LCHF as one of the diet options for people with type 2 diabetes,” Dr. Hansen said in a written comment, considering all available data.

Although the diet did lead to significant clinical benefits, she predicted that some patients would still struggle with adherence in the real world.

“The LCHF diet can be difficult for some people to follow,” Dr. Hansen said. “It is a bit more expensive, and it can be difficult to comply to in social gatherings, simply because our society is not suited for this type of diet.”
 

The magic of unrestricted calories

Jay H. Shubrook, DO, diabetologist and professor at Touro University of California, Vallejo, offered a similar view.

“When you start to fiddle with the diet, it affects not only the person, but all the people they eat with, because eating is a communal experience,” Dr. Shubrook said, in an interview.

Still, he said the present study is “a big deal,” because T2D is a “noncommunicable pandemic,” and “anything we could do that disrupts this process is very important.”

While some may struggle to follow the LCHF diet, Dr. Shubrook predicted better long-term adherence than the low-calorie diet usually recommended.

“What’s magic about this study is because it wasn’t calorie restricted, I think it made it a little bit more flexible for people to continue,” Dr. Shubrook said.

He added that he thinks patients will need a fair amount of coaching and education about food choices in order to lose weight on a diet without calorie restrictions.
 

Not the first study of its kind

In a written comment, Jeff Volek, PhD, RD, professor at the Ohio State University, Columbus, called the present study “another important piece of work, demonstrating yet again, that a low-carbohydrate eating pattern is superior to a high-carbohydrate approach in people with insulin resistance.”

Yet Dr. Volek, who has conducted numerous studies on low-carbohydrate diets, also said there is “little here that is new or surprising.”

He went on to admonish Dr. Hansen and colleagues for failing to recognize those who have already broken ground in this area.

“Unfortunately, these authors do not give credit to the many researchers who have published extensively on low-carbohydrate diets in the past, and instead make claims about being the first to study a calorie unrestricted low-carb diet in individuals with T2D, which is clearly not the case,” Dr. Volek said. “There is a large body of literature showing similar findings with better control over diet, larger cohorts, longer follow-up, and more comprehensive biomarker assessment.”

He noted that data supporting low-carb diets for T2D have been sufficient since at least 2019, when the American Diabetes Association updated their guidance on the subject.

Citing a paper published in Diabetes Care, he said, “Low-carbohydrate eating patterns, especially very-low-carbohydrate eating patterns, have been shown to reduce A1C and the need for antihyperglycemic medications.”

The study was funded by Novo Nordisk Foundation, Danish Diabetes Academy, Odense University Hospital, and others. The investigators disclosed additional relationships with Eli Lilly, Amgen, UCB, and others. Dr. Shubrook disclosed relationships with Abbot, AstraZeneca, Bayer, and others.

Eating a low-carbohydrate, high-fat (LCHF) diet, instead of a high-carbohydrate, low-fat diet (HCLF), leads to significant improvements in type 2 diabetes (T2D), a new study finds.

This was true regardless of an individual’s calorie intake, in the randomized controlled trial published in the Annals of Internal Medicine.

Patients with T2D who ate a low-carb, high-fat diet (LCHF) lost more weight and saw greater improvements in both glycemic control and insulin resistance than those who ate a high-carb, low-fat diet (HCLF), reported lead author Camilla Dalby Hansen, MD, of University of Southern Denmark, Odense, and colleagues, suggesting that this is an effective, nonpharmaceutical treatment option for T2D.

The trial enrolled 185 patients with T2D, for whom low-calorie diets are often recommended to induce weight loss and improve glycemic control.

The trouble with this common recommendation, the investigators wrote, is that it induces hunger, so few patients stick to it.

“Therefore, calorie-unrestricted diets may be a better alternative to achieve long-term maintenance,” Dr. Hansen and colleagues wrote, noting that this approach “is not widely investigated.”
 

Study methods and results

In the new study, participants were randomized in a 2:1 ratio to follow the LCHF or HCLF diet for 6 months, with no restriction on calorie intake. Patients were evaluated at baseline, 3 months, 6 months, and 9 months (3 months after discontinuation). Parameters included glycemic control, serum lipid levels, and metabolic markers. The final analysis included 165 patients.

While patients in both groups lost weight, those in the LCHF group lost, on average, about 8 pounds more than the HCLF group, a significant difference. While the LCHF diet was associated with greater improvements in glycemic control (HbA1c) than the HCLF diet, it also led to slightly greater increases in LDL levels. In both groups, HDL levels increased, and triglycerides decreased, without significant differences between groups.

The above changes were not sustained 3 months after finishing the diet.

“I believe we have sufficient data to include LCHF as one of the diet options for people with type 2 diabetes,” Dr. Hansen said in a written comment, considering all available data.

Although the diet did lead to significant clinical benefits, she predicted that some patients would still struggle with adherence in the real world.

“The LCHF diet can be difficult for some people to follow,” Dr. Hansen said. “It is a bit more expensive, and it can be difficult to comply to in social gatherings, simply because our society is not suited for this type of diet.”
 

The magic of unrestricted calories

Jay H. Shubrook, DO, diabetologist and professor at Touro University of California, Vallejo, offered a similar view.

“When you start to fiddle with the diet, it affects not only the person, but all the people they eat with, because eating is a communal experience,” Dr. Shubrook said, in an interview.

Still, he said the present study is “a big deal,” because T2D is a “noncommunicable pandemic,” and “anything we could do that disrupts this process is very important.”

While some may struggle to follow the LCHF diet, Dr. Shubrook predicted better long-term adherence than the low-calorie diet usually recommended.

“What’s magic about this study is because it wasn’t calorie restricted, I think it made it a little bit more flexible for people to continue,” Dr. Shubrook said.

He added that he thinks patients will need a fair amount of coaching and education about food choices in order to lose weight on a diet without calorie restrictions.
 

Not the first study of its kind

In a written comment, Jeff Volek, PhD, RD, professor at the Ohio State University, Columbus, called the present study “another important piece of work, demonstrating yet again, that a low-carbohydrate eating pattern is superior to a high-carbohydrate approach in people with insulin resistance.”

Yet Dr. Volek, who has conducted numerous studies on low-carbohydrate diets, also said there is “little here that is new or surprising.”

He went on to admonish Dr. Hansen and colleagues for failing to recognize those who have already broken ground in this area.

“Unfortunately, these authors do not give credit to the many researchers who have published extensively on low-carbohydrate diets in the past, and instead make claims about being the first to study a calorie unrestricted low-carb diet in individuals with T2D, which is clearly not the case,” Dr. Volek said. “There is a large body of literature showing similar findings with better control over diet, larger cohorts, longer follow-up, and more comprehensive biomarker assessment.”

He noted that data supporting low-carb diets for T2D have been sufficient since at least 2019, when the American Diabetes Association updated their guidance on the subject.

Citing a paper published in Diabetes Care, he said, “Low-carbohydrate eating patterns, especially very-low-carbohydrate eating patterns, have been shown to reduce A1C and the need for antihyperglycemic medications.”

The study was funded by Novo Nordisk Foundation, Danish Diabetes Academy, Odense University Hospital, and others. The investigators disclosed additional relationships with Eli Lilly, Amgen, UCB, and others. Dr. Shubrook disclosed relationships with Abbot, AstraZeneca, Bayer, and others.

Eating a low-carbohydrate, high-fat (LCHF) diet, instead of a high-carbohydrate, low-fat diet (HCLF), leads to significant improvements in type 2 diabetes (T2D), a new study finds.

This was true regardless of an individual’s calorie intake, in the randomized controlled trial published in the Annals of Internal Medicine.

Patients with T2D who ate a low-carb, high-fat diet (LCHF) lost more weight and saw greater improvements in both glycemic control and insulin resistance than those who ate a high-carb, low-fat diet (HCLF), reported lead author Camilla Dalby Hansen, MD, of University of Southern Denmark, Odense, and colleagues, suggesting that this is an effective, nonpharmaceutical treatment option for T2D.

The trial enrolled 185 patients with T2D, for whom low-calorie diets are often recommended to induce weight loss and improve glycemic control.

The trouble with this common recommendation, the investigators wrote, is that it induces hunger, so few patients stick to it.

“Therefore, calorie-unrestricted diets may be a better alternative to achieve long-term maintenance,” Dr. Hansen and colleagues wrote, noting that this approach “is not widely investigated.”
 

Study methods and results

In the new study, participants were randomized in a 2:1 ratio to follow the LCHF or HCLF diet for 6 months, with no restriction on calorie intake. Patients were evaluated at baseline, 3 months, 6 months, and 9 months (3 months after discontinuation). Parameters included glycemic control, serum lipid levels, and metabolic markers. The final analysis included 165 patients.

While patients in both groups lost weight, those in the LCHF group lost, on average, about 8 pounds more than the HCLF group, a significant difference. While the LCHF diet was associated with greater improvements in glycemic control (HbA1c) than the HCLF diet, it also led to slightly greater increases in LDL levels. In both groups, HDL levels increased, and triglycerides decreased, without significant differences between groups.

The above changes were not sustained 3 months after finishing the diet.

“I believe we have sufficient data to include LCHF as one of the diet options for people with type 2 diabetes,” Dr. Hansen said in a written comment, considering all available data.

Although the diet did lead to significant clinical benefits, she predicted that some patients would still struggle with adherence in the real world.

“The LCHF diet can be difficult for some people to follow,” Dr. Hansen said. “It is a bit more expensive, and it can be difficult to comply to in social gatherings, simply because our society is not suited for this type of diet.”
 

The magic of unrestricted calories

Jay H. Shubrook, DO, diabetologist and professor at Touro University of California, Vallejo, offered a similar view.

“When you start to fiddle with the diet, it affects not only the person, but all the people they eat with, because eating is a communal experience,” Dr. Shubrook said, in an interview.

Still, he said the present study is “a big deal,” because T2D is a “noncommunicable pandemic,” and “anything we could do that disrupts this process is very important.”

While some may struggle to follow the LCHF diet, Dr. Shubrook predicted better long-term adherence than the low-calorie diet usually recommended.

“What’s magic about this study is because it wasn’t calorie restricted, I think it made it a little bit more flexible for people to continue,” Dr. Shubrook said.

He added that he thinks patients will need a fair amount of coaching and education about food choices in order to lose weight on a diet without calorie restrictions.
 

Not the first study of its kind

In a written comment, Jeff Volek, PhD, RD, professor at the Ohio State University, Columbus, called the present study “another important piece of work, demonstrating yet again, that a low-carbohydrate eating pattern is superior to a high-carbohydrate approach in people with insulin resistance.”

Yet Dr. Volek, who has conducted numerous studies on low-carbohydrate diets, also said there is “little here that is new or surprising.”

He went on to admonish Dr. Hansen and colleagues for failing to recognize those who have already broken ground in this area.

“Unfortunately, these authors do not give credit to the many researchers who have published extensively on low-carbohydrate diets in the past, and instead make claims about being the first to study a calorie unrestricted low-carb diet in individuals with T2D, which is clearly not the case,” Dr. Volek said. “There is a large body of literature showing similar findings with better control over diet, larger cohorts, longer follow-up, and more comprehensive biomarker assessment.”

He noted that data supporting low-carb diets for T2D have been sufficient since at least 2019, when the American Diabetes Association updated their guidance on the subject.

Citing a paper published in Diabetes Care, he said, “Low-carbohydrate eating patterns, especially very-low-carbohydrate eating patterns, have been shown to reduce A1C and the need for antihyperglycemic medications.”

The study was funded by Novo Nordisk Foundation, Danish Diabetes Academy, Odense University Hospital, and others. The investigators disclosed additional relationships with Eli Lilly, Amgen, UCB, and others. Dr. Shubrook disclosed relationships with Abbot, AstraZeneca, Bayer, and others.