Clinical Endocrinology News

An influential panel is seeking an increase in Medicare’s 2025 payments for clinicians, adding to pressure on Congress to reconsider how the largest US purchaser of health services pays for office visits and related care of the nation’s older citizens and those with disabilities.

The Medicare Payment Advisory Commission (MedPAC) on Thursday voted unanimously in favor of a two-part recommendation on changes to the 2025 physician fee schedule:

• An increase in the base rate equal to half of the projected change in the Medicare Economic Index (MEI). Recent estimates have projected a 2.6% increase in MEI for 2025, which is intended to show how inflation affects the costs of running a medical practice.
• The creation of a safety-net add-on payment under the physician fee schedule to cover care of people with low incomes.

These recommendations echo the calls MedPAC made in a 2023 report to Congress. 

Lawmakers and the Centers for Medicare and Medicaid Services (CMS) rely on MedPAC’s work in deciding how much to pay for services. About 1.3 million clinicians bill Medicare for their work, including about 670,000 physicians.

Thursday’s MedPAC vote comes amid continuing uncertainty about how much the federal government will actually pay clinicians this year through the physician fee schedule.

There are serious efforts underway to undo cuts already demanded by previously passed federal law. In an email, Rep. Larry Buchson, MD, (R-IN) said he remains committed to “eliminating the full 3.37% cut this year while also working toward a permanent solution to halt the downward spiral of physician reimbursement.”

“The Medicare payment cut to physicians will impede patients’ access to care and further accelerate the current path toward consolidation, physician burnout, and closure of medical practices,” Buchson told this news organization. “It’s past time that Congress provides much needed and deserved stability for America’s doctors.”

Congress this month is attempting to complete overdue budget legislation needed to fund federal operations for fiscal 2024, which began October 1, 2023. The pending expiration of a short-term stopgap continuing resolution could provide a vehicle that could also carry legislation that would address the physician fee schedule.

In a Thursday statement, Jesse M. Ehrenfeld, MD, MPH, president of the American Medical Association, commended MedPAC for its recommendations and urged lawmakers to act.

“Long-term reforms from Congress are overdue to close the unsustainable gap between what Medicare pays physicians and the actual costs of delivering high-quality care,” Dr. Ehrenfeld said. “When adjusted for inflation in practice costs, Medicare physician pay declined 26% from 2001 to 2023.”
 

Continual Struggles

Congress has struggled for years in its attempts to set Medicare payments for office visits and other services covered by the physician fee schedule. A 1990s budget law set the stage for what proved to be untenable reductions in payment through the sustainable growth rate mechanism.

Between 2003 through April 2014, lawmakers passed “doc-fix” legislation 17 times to block the slated cuts, according to the Congressional Research Service. In 2015, Congress passed an intended overhaul of the physician fee schedule through the Medicare Access and CHIP Reauthorization Act (MACRA). As part of this law, Congress eliminated a base automatic inflation adjuster for the physician fee schedule.

In recent years, Congress has acted repeatedly to address MACRA’s mandates for flat base pay. MedPAC and members of both parties in Congress have called for a broad new look at how Medicare pays physicians. 

At Thursday’s meeting, MedPAC member Lawrence Casalino, MD, PhD, MPH, noted that the struggles to keep up with inflation and the “unpredictability of what the payment rates are going to be from year to year really do affect physician morale.”

A version of this article appeared on Medscape.com.

An influential panel is seeking an increase in Medicare’s 2025 payments for clinicians, adding to pressure on Congress to reconsider how the largest US purchaser of health services pays for office visits and related care of the nation’s older citizens and those with disabilities.

The Medicare Payment Advisory Commission (MedPAC) on Thursday voted unanimously in favor of a two-part recommendation on changes to the 2025 physician fee schedule:

• An increase in the base rate equal to half of the projected change in the Medicare Economic Index (MEI). Recent estimates have projected a 2.6% increase in MEI for 2025, which is intended to show how inflation affects the costs of running a medical practice.
• The creation of a safety-net add-on payment under the physician fee schedule to cover care of people with low incomes.

These recommendations echo the calls MedPAC made in a 2023 report to Congress. 

Lawmakers and the Centers for Medicare and Medicaid Services (CMS) rely on MedPAC’s work in deciding how much to pay for services. About 1.3 million clinicians bill Medicare for their work, including about 670,000 physicians.

Thursday’s MedPAC vote comes amid continuing uncertainty about how much the federal government will actually pay clinicians this year through the physician fee schedule.

There are serious efforts underway to undo cuts already demanded by previously passed federal law. In an email, Rep. Larry Buchson, MD, (R-IN) said he remains committed to “eliminating the full 3.37% cut this year while also working toward a permanent solution to halt the downward spiral of physician reimbursement.”

“The Medicare payment cut to physicians will impede patients’ access to care and further accelerate the current path toward consolidation, physician burnout, and closure of medical practices,” Buchson told this news organization. “It’s past time that Congress provides much needed and deserved stability for America’s doctors.”

Congress this month is attempting to complete overdue budget legislation needed to fund federal operations for fiscal 2024, which began October 1, 2023. The pending expiration of a short-term stopgap continuing resolution could provide a vehicle that could also carry legislation that would address the physician fee schedule.

In a Thursday statement, Jesse M. Ehrenfeld, MD, MPH, president of the American Medical Association, commended MedPAC for its recommendations and urged lawmakers to act.

“Long-term reforms from Congress are overdue to close the unsustainable gap between what Medicare pays physicians and the actual costs of delivering high-quality care,” Dr. Ehrenfeld said. “When adjusted for inflation in practice costs, Medicare physician pay declined 26% from 2001 to 2023.”
 

Continual Struggles

Congress has struggled for years in its attempts to set Medicare payments for office visits and other services covered by the physician fee schedule. A 1990s budget law set the stage for what proved to be untenable reductions in payment through the sustainable growth rate mechanism.

Between 2003 through April 2014, lawmakers passed “doc-fix” legislation 17 times to block the slated cuts, according to the Congressional Research Service. In 2015, Congress passed an intended overhaul of the physician fee schedule through the Medicare Access and CHIP Reauthorization Act (MACRA). As part of this law, Congress eliminated a base automatic inflation adjuster for the physician fee schedule.

In recent years, Congress has acted repeatedly to address MACRA’s mandates for flat base pay. MedPAC and members of both parties in Congress have called for a broad new look at how Medicare pays physicians. 

At Thursday’s meeting, MedPAC member Lawrence Casalino, MD, PhD, MPH, noted that the struggles to keep up with inflation and the “unpredictability of what the payment rates are going to be from year to year really do affect physician morale.”

A version of this article appeared on Medscape.com.

An influential panel is seeking an increase in Medicare’s 2025 payments for clinicians, adding to pressure on Congress to reconsider how the largest US purchaser of health services pays for office visits and related care of the nation’s older citizens and those with disabilities.

The Medicare Payment Advisory Commission (MedPAC) on Thursday voted unanimously in favor of a two-part recommendation on changes to the 2025 physician fee schedule:

• An increase in the base rate equal to half of the projected change in the Medicare Economic Index (MEI). Recent estimates have projected a 2.6% increase in MEI for 2025, which is intended to show how inflation affects the costs of running a medical practice.
• The creation of a safety-net add-on payment under the physician fee schedule to cover care of people with low incomes.

These recommendations echo the calls MedPAC made in a 2023 report to Congress. 

Lawmakers and the Centers for Medicare and Medicaid Services (CMS) rely on MedPAC’s work in deciding how much to pay for services. About 1.3 million clinicians bill Medicare for their work, including about 670,000 physicians.

Thursday’s MedPAC vote comes amid continuing uncertainty about how much the federal government will actually pay clinicians this year through the physician fee schedule.

There are serious efforts underway to undo cuts already demanded by previously passed federal law. In an email, Rep. Larry Buchson, MD, (R-IN) said he remains committed to “eliminating the full 3.37% cut this year while also working toward a permanent solution to halt the downward spiral of physician reimbursement.”

“The Medicare payment cut to physicians will impede patients’ access to care and further accelerate the current path toward consolidation, physician burnout, and closure of medical practices,” Buchson told this news organization. “It’s past time that Congress provides much needed and deserved stability for America’s doctors.”

Congress this month is attempting to complete overdue budget legislation needed to fund federal operations for fiscal 2024, which began October 1, 2023. The pending expiration of a short-term stopgap continuing resolution could provide a vehicle that could also carry legislation that would address the physician fee schedule.

In a Thursday statement, Jesse M. Ehrenfeld, MD, MPH, president of the American Medical Association, commended MedPAC for its recommendations and urged lawmakers to act.

“Long-term reforms from Congress are overdue to close the unsustainable gap between what Medicare pays physicians and the actual costs of delivering high-quality care,” Dr. Ehrenfeld said. “When adjusted for inflation in practice costs, Medicare physician pay declined 26% from 2001 to 2023.”
 

Continual Struggles

Congress has struggled for years in its attempts to set Medicare payments for office visits and other services covered by the physician fee schedule. A 1990s budget law set the stage for what proved to be untenable reductions in payment through the sustainable growth rate mechanism.

Between 2003 through April 2014, lawmakers passed “doc-fix” legislation 17 times to block the slated cuts, according to the Congressional Research Service. In 2015, Congress passed an intended overhaul of the physician fee schedule through the Medicare Access and CHIP Reauthorization Act (MACRA). As part of this law, Congress eliminated a base automatic inflation adjuster for the physician fee schedule.

In recent years, Congress has acted repeatedly to address MACRA’s mandates for flat base pay. MedPAC and members of both parties in Congress have called for a broad new look at how Medicare pays physicians. 

At Thursday’s meeting, MedPAC member Lawrence Casalino, MD, PhD, MPH, noted that the struggles to keep up with inflation and the “unpredictability of what the payment rates are going to be from year to year really do affect physician morale.”

A version of this article appeared on Medscape.com.

To lose weight, patients with obesity may be more interested in semaglutide products, but the glucagon-like peptide I agonists, such as Ozempic injections and Rybelsus tablets, are not yet cost-effective, according to a modeling study that compared the drugs with surgery and endoscopy.

Sleeve gastrectomy (SG) for moderate to severe (class II/III) obesity and the less invasive endoscopic sleeve gastroplasty (ESG) for mild (class I) obesity were both cost effective strategies to reduce obesity, the researchers report.

“SG should be offered as the first-line treatment for class II and class III obesity,” write Monica Saumoy, MD, of the Center for Digestive Health, Penn Medicine Princeton Medical Center, Plainsboro, N.J., and coauthors. “ESG is an effective and cost-effective nonsurgical treatment for class I, class II and class III obesity, and more efforts are needed to ensure that patients have access to this procedure.

Penn Medicine

“While semaglutide is highly effective for weight loss, and there is substantial patient interest, it is not currently cost-effective due to its high cost,” they add. “With methods to reduce semaglutide’s annual cost, it may provide an effective and cost-effective method to reduce the morbidity related to obesity.”

The study was published in Gut.
 

Cost Concerns

One in two Americans will likely be obese by 2030, according to current models, and nearly one in four adults will be severely obese.

Several weight-loss therapies exist to treat obesity. Evidence shows bariatric surgery is effective in reducing weight, metabolic comorbidities, and mortality in people with obesity compared with lifestyle intervention alone, but surgery has risks, adverse events, and poor national uptake. Patients are likely more interested in less invasive options, the authors write.

Recent trials have reported effective weight loss from less invasive options. A five-year follow-up of the randomized controlled MERIT trial found that ESG was associated with a 13.6% total body weight loss for people with mild to moderate obesity.

On the pharmaceutical front, other randomized controlled trials have shown that semaglutide is linked with as much as 17% total body weight loss at two years. Also, recent guidance from the American Gastroenterological Association (AGA) states that long-term treatment with a semaglutide is the preferred strategy for weight loss.

“However, concerns about the cost and the cost-effectiveness of these [less invasive] interventions have limited their usage in the USA,” the study authors write.

The aim of the study was to perform a cost-effectiveness analysis comparing SG, ESG, semaglutide, and lifestyle interventions (LI) for patients with obesity in class I (defined as BMI 30-34.9 kg/m²), class II (35-29.9 kg/m²), and class III (>40kg/m²) obesity.

Researchers used a state-transition, semi-Markov microsimulation model to analyze the effectiveness of ESG, SG, semaglutide, and LI in a simulated 40-year-old with three different base-case scenarios of class I, II, or III obesity. They then performed a detailed threshold and sensitivity analysis to change the cost of treatment modalities and the semaglutide adherence rate. Outcome measures included a willingness-to-pay threshold of US $100,000/quality-adjusted life years (QALY) and incremental cost-effectiveness ratios (ICERs).
 

Cost-Effectiveness of Treatments

When the treatment modalities were compared with each other, findings showed that for class I obesity, ESG was cost effective (US $4,105/QALY). For class II and III obesity, SG was cost-effective as well (US $5,883/QALY) and (US $7,821/QALY), respectively.

In all classes of obesity, SG and ESG were cost-effective compared with LI. Semaglutide was not cost-effective compared with LI for class I, II, and III obesity (ICER US $508,414/QALY, $420,483/QALY, and $350,637/QALY, respectively).

“For semaglutide to be cost-effective when compared with ESG, it would have to cost less than US $1,879 (class III), US $1,204 (class II), or US $297 (class I) annually,” the authors note.

The authors addressed recent guidelines to consider bariatric surgery in all obese patients. They recommend SG remain the standard of care for patients with severe obesity.

But national projections show that SG would address only 0.5% of life-years lost due to obesity.

“Barring a dramatic increase in patient adherence, bariatric surgery will not likely successfully mitigate the harm from the obesity epidemic,” they write.

“ESG may fill this gap and provide an additional option for patients with obesity as it demonstrated sustained weight loss at 2-5 years.” While insurance coverage is limited, they write, “our model demonstrates that payer coverage for ESG would provide an alternative tool to combat the obesity epidemic as part of a multidisciplinary approach.”

Semaglutide shows sustained weight loss in trials for up to two years but has a substantial annual cost, the authors note.

At lower prices, semaglutide can make a “major impact on the obesity pandemic as it can be prescribed in multiple healthcare settings and due to increased patient interested in non-invasive obesity treatment,” they write.

One limitation to the study is a lack of long-term data available for ESG and semaglutide. Authors were also not able to use a lifetime horizon because of a lack of long-term weight loss.

One study author reports financial relationships with BSC, Cook Medical, Surgical Intuitive, and Olympus America. Another author reports relationships with ACI, AGA-Varia, BSC, Dark Canyon Labs, Endiatx, Medtronic, Olympus, Virgo Systems; equity: AGA-Varia, Dark Canyon Labs, Endiatx, EndoSound, and Virgo Systems. The rest of the authors have no conflicts to disclose.

To lose weight, patients with obesity may be more interested in semaglutide products, but the glucagon-like peptide I agonists, such as Ozempic injections and Rybelsus tablets, are not yet cost-effective, according to a modeling study that compared the drugs with surgery and endoscopy.

Sleeve gastrectomy (SG) for moderate to severe (class II/III) obesity and the less invasive endoscopic sleeve gastroplasty (ESG) for mild (class I) obesity were both cost effective strategies to reduce obesity, the researchers report.

“SG should be offered as the first-line treatment for class II and class III obesity,” write Monica Saumoy, MD, of the Center for Digestive Health, Penn Medicine Princeton Medical Center, Plainsboro, N.J., and coauthors. “ESG is an effective and cost-effective nonsurgical treatment for class I, class II and class III obesity, and more efforts are needed to ensure that patients have access to this procedure.

Penn Medicine

“While semaglutide is highly effective for weight loss, and there is substantial patient interest, it is not currently cost-effective due to its high cost,” they add. “With methods to reduce semaglutide’s annual cost, it may provide an effective and cost-effective method to reduce the morbidity related to obesity.”

The study was published in Gut.
 

Cost Concerns

One in two Americans will likely be obese by 2030, according to current models, and nearly one in four adults will be severely obese.

Several weight-loss therapies exist to treat obesity. Evidence shows bariatric surgery is effective in reducing weight, metabolic comorbidities, and mortality in people with obesity compared with lifestyle intervention alone, but surgery has risks, adverse events, and poor national uptake. Patients are likely more interested in less invasive options, the authors write.

Recent trials have reported effective weight loss from less invasive options. A five-year follow-up of the randomized controlled MERIT trial found that ESG was associated with a 13.6% total body weight loss for people with mild to moderate obesity.

On the pharmaceutical front, other randomized controlled trials have shown that semaglutide is linked with as much as 17% total body weight loss at two years. Also, recent guidance from the American Gastroenterological Association (AGA) states that long-term treatment with a semaglutide is the preferred strategy for weight loss.

“However, concerns about the cost and the cost-effectiveness of these [less invasive] interventions have limited their usage in the USA,” the study authors write.

The aim of the study was to perform a cost-effectiveness analysis comparing SG, ESG, semaglutide, and lifestyle interventions (LI) for patients with obesity in class I (defined as BMI 30-34.9 kg/m²), class II (35-29.9 kg/m²), and class III (>40kg/m²) obesity.

Researchers used a state-transition, semi-Markov microsimulation model to analyze the effectiveness of ESG, SG, semaglutide, and LI in a simulated 40-year-old with three different base-case scenarios of class I, II, or III obesity. They then performed a detailed threshold and sensitivity analysis to change the cost of treatment modalities and the semaglutide adherence rate. Outcome measures included a willingness-to-pay threshold of US $100,000/quality-adjusted life years (QALY) and incremental cost-effectiveness ratios (ICERs).
 

Cost-Effectiveness of Treatments

When the treatment modalities were compared with each other, findings showed that for class I obesity, ESG was cost effective (US $4,105/QALY). For class II and III obesity, SG was cost-effective as well (US $5,883/QALY) and (US $7,821/QALY), respectively.

In all classes of obesity, SG and ESG were cost-effective compared with LI. Semaglutide was not cost-effective compared with LI for class I, II, and III obesity (ICER US $508,414/QALY, $420,483/QALY, and $350,637/QALY, respectively).

“For semaglutide to be cost-effective when compared with ESG, it would have to cost less than US $1,879 (class III), US $1,204 (class II), or US $297 (class I) annually,” the authors note.

The authors addressed recent guidelines to consider bariatric surgery in all obese patients. They recommend SG remain the standard of care for patients with severe obesity.

But national projections show that SG would address only 0.5% of life-years lost due to obesity.

“Barring a dramatic increase in patient adherence, bariatric surgery will not likely successfully mitigate the harm from the obesity epidemic,” they write.

“ESG may fill this gap and provide an additional option for patients with obesity as it demonstrated sustained weight loss at 2-5 years.” While insurance coverage is limited, they write, “our model demonstrates that payer coverage for ESG would provide an alternative tool to combat the obesity epidemic as part of a multidisciplinary approach.”

Semaglutide shows sustained weight loss in trials for up to two years but has a substantial annual cost, the authors note.

At lower prices, semaglutide can make a “major impact on the obesity pandemic as it can be prescribed in multiple healthcare settings and due to increased patient interested in non-invasive obesity treatment,” they write.

One limitation to the study is a lack of long-term data available for ESG and semaglutide. Authors were also not able to use a lifetime horizon because of a lack of long-term weight loss.

One study author reports financial relationships with BSC, Cook Medical, Surgical Intuitive, and Olympus America. Another author reports relationships with ACI, AGA-Varia, BSC, Dark Canyon Labs, Endiatx, Medtronic, Olympus, Virgo Systems; equity: AGA-Varia, Dark Canyon Labs, Endiatx, EndoSound, and Virgo Systems. The rest of the authors have no conflicts to disclose.

To lose weight, patients with obesity may be more interested in semaglutide products, but the glucagon-like peptide I agonists, such as Ozempic injections and Rybelsus tablets, are not yet cost-effective, according to a modeling study that compared the drugs with surgery and endoscopy.

Sleeve gastrectomy (SG) for moderate to severe (class II/III) obesity and the less invasive endoscopic sleeve gastroplasty (ESG) for mild (class I) obesity were both cost effective strategies to reduce obesity, the researchers report.

“SG should be offered as the first-line treatment for class II and class III obesity,” write Monica Saumoy, MD, of the Center for Digestive Health, Penn Medicine Princeton Medical Center, Plainsboro, N.J., and coauthors. “ESG is an effective and cost-effective nonsurgical treatment for class I, class II and class III obesity, and more efforts are needed to ensure that patients have access to this procedure.

Penn Medicine

“While semaglutide is highly effective for weight loss, and there is substantial patient interest, it is not currently cost-effective due to its high cost,” they add. “With methods to reduce semaglutide’s annual cost, it may provide an effective and cost-effective method to reduce the morbidity related to obesity.”

The study was published in Gut.
 

Cost Concerns

One in two Americans will likely be obese by 2030, according to current models, and nearly one in four adults will be severely obese.

Several weight-loss therapies exist to treat obesity. Evidence shows bariatric surgery is effective in reducing weight, metabolic comorbidities, and mortality in people with obesity compared with lifestyle intervention alone, but surgery has risks, adverse events, and poor national uptake. Patients are likely more interested in less invasive options, the authors write.

Recent trials have reported effective weight loss from less invasive options. A five-year follow-up of the randomized controlled MERIT trial found that ESG was associated with a 13.6% total body weight loss for people with mild to moderate obesity.

On the pharmaceutical front, other randomized controlled trials have shown that semaglutide is linked with as much as 17% total body weight loss at two years. Also, recent guidance from the American Gastroenterological Association (AGA) states that long-term treatment with a semaglutide is the preferred strategy for weight loss.

“However, concerns about the cost and the cost-effectiveness of these [less invasive] interventions have limited their usage in the USA,” the study authors write.

The aim of the study was to perform a cost-effectiveness analysis comparing SG, ESG, semaglutide, and lifestyle interventions (LI) for patients with obesity in class I (defined as BMI 30-34.9 kg/m²), class II (35-29.9 kg/m²), and class III (>40kg/m²) obesity.

Researchers used a state-transition, semi-Markov microsimulation model to analyze the effectiveness of ESG, SG, semaglutide, and LI in a simulated 40-year-old with three different base-case scenarios of class I, II, or III obesity. They then performed a detailed threshold and sensitivity analysis to change the cost of treatment modalities and the semaglutide adherence rate. Outcome measures included a willingness-to-pay threshold of US $100,000/quality-adjusted life years (QALY) and incremental cost-effectiveness ratios (ICERs).
 

Cost-Effectiveness of Treatments

When the treatment modalities were compared with each other, findings showed that for class I obesity, ESG was cost effective (US $4,105/QALY). For class II and III obesity, SG was cost-effective as well (US $5,883/QALY) and (US $7,821/QALY), respectively.

In all classes of obesity, SG and ESG were cost-effective compared with LI. Semaglutide was not cost-effective compared with LI for class I, II, and III obesity (ICER US $508,414/QALY, $420,483/QALY, and $350,637/QALY, respectively).

“For semaglutide to be cost-effective when compared with ESG, it would have to cost less than US $1,879 (class III), US $1,204 (class II), or US $297 (class I) annually,” the authors note.

The authors addressed recent guidelines to consider bariatric surgery in all obese patients. They recommend SG remain the standard of care for patients with severe obesity.

But national projections show that SG would address only 0.5% of life-years lost due to obesity.

“Barring a dramatic increase in patient adherence, bariatric surgery will not likely successfully mitigate the harm from the obesity epidemic,” they write.

“ESG may fill this gap and provide an additional option for patients with obesity as it demonstrated sustained weight loss at 2-5 years.” While insurance coverage is limited, they write, “our model demonstrates that payer coverage for ESG would provide an alternative tool to combat the obesity epidemic as part of a multidisciplinary approach.”

Semaglutide shows sustained weight loss in trials for up to two years but has a substantial annual cost, the authors note.

At lower prices, semaglutide can make a “major impact on the obesity pandemic as it can be prescribed in multiple healthcare settings and due to increased patient interested in non-invasive obesity treatment,” they write.

One limitation to the study is a lack of long-term data available for ESG and semaglutide. Authors were also not able to use a lifetime horizon because of a lack of long-term weight loss.

One study author reports financial relationships with BSC, Cook Medical, Surgical Intuitive, and Olympus America. Another author reports relationships with ACI, AGA-Varia, BSC, Dark Canyon Labs, Endiatx, Medtronic, Olympus, Virgo Systems; equity: AGA-Varia, Dark Canyon Labs, Endiatx, EndoSound, and Virgo Systems. The rest of the authors have no conflicts to disclose.

TOPLINE:

Patients with type 2 diabetes (T2D) at an elevated risk for kidney failure may stand to gain the most renal benefit with intensive glycemic control, but they also face the highest overall risk for death and hypoglycemic events.

METHODOLOGY:

• Studies show the primary benefit of intensive glycemic control in T2D is microvascular outcomes, mostly in the kidney, but no clear criteria exist to identify patients who may benefit most.
• Researchers conducted a post hoc analysis of the ACCORD trial, including 9777 patients with diabetes and cardiovascular disease or two or more cardiovascular risk factors.
• The 5-year kidney failure risk was estimated using the validated kidney failure risk equation (KFRE).
• The patients were randomly assigned to receive intensive glycemic control (A1c, < 6.0%) or standard glycemic control (A1c, 7.0%-7.9%).
• The primary outcomes were kidney microvascular events and all-cause mortality.

TAKEAWAY:

• Over a 7-year period, intensive vs standard glycemic control delayed the onset of kidney microvascular outcomes by 48.4 days (corresponding hazard ratio [HR], 0.75; 95% CI, 0.65-0.86) but reduced the time to death by 23.6 days (HR, 1.20; 95% CI, 1.04-1.40).
• Patients in the highest quartile of 5-year kidney failure risk according to KFRE benefited the most with intensive vs standard glycemic control and reported the longest delay in the onset of kidney microvascular outcomes (114.8 days; 95% CI, 58.1-176.4).
• Although renal outcomes improved, the time to death was shortened by 56.7 days in patients with elevated risk for kidney failure receiving intensive glycemic control.

IN PRACTICE:

“The observed effect of intensive glycemic control on kidney microvascular outcomes in ACCORD is almost entirely driven by a subset of patients representing one quarter of the trial eligible population at elevated risk for kidney failure at baseline,” the authors wrote.

SOURCE:

Vivek Charu of Stanford University School of Medicine, Stanford, California, led this study, which was published online on December 11, 2023, in the Journal of the American Society of Nephrology

LIMITATIONS:

The ACCORD study enrolled participants with a low risk for kidney disease. Therefore, this study lacks relevant data that might be needed to analyze the risks and benefits of intensive glycemic control in a population at high risk for kidney disease. Treatment options and monitoring approaches to glycemic control have evolved in the nearly 20 years since the ACCORD trial, which used insulin and sulfonylurea agents for glycemic control.

DISCLOSURES:

This work was supported by several grants secured by the authors. Some authors declared serving in advisory or leadership roles, receiving honoraria and research funding, and other ties with several sources.

A version of this article appeared on Medscape.com.

TOPLINE:

Patients with type 2 diabetes (T2D) at an elevated risk for kidney failure may stand to gain the most renal benefit with intensive glycemic control, but they also face the highest overall risk for death and hypoglycemic events.

METHODOLOGY:

• Studies show the primary benefit of intensive glycemic control in T2D is microvascular outcomes, mostly in the kidney, but no clear criteria exist to identify patients who may benefit most.
• Researchers conducted a post hoc analysis of the ACCORD trial, including 9777 patients with diabetes and cardiovascular disease or two or more cardiovascular risk factors.
• The 5-year kidney failure risk was estimated using the validated kidney failure risk equation (KFRE).
• The patients were randomly assigned to receive intensive glycemic control (A1c, < 6.0%) or standard glycemic control (A1c, 7.0%-7.9%).
• The primary outcomes were kidney microvascular events and all-cause mortality.

TAKEAWAY:

• Over a 7-year period, intensive vs standard glycemic control delayed the onset of kidney microvascular outcomes by 48.4 days (corresponding hazard ratio [HR], 0.75; 95% CI, 0.65-0.86) but reduced the time to death by 23.6 days (HR, 1.20; 95% CI, 1.04-1.40).
• Patients in the highest quartile of 5-year kidney failure risk according to KFRE benefited the most with intensive vs standard glycemic control and reported the longest delay in the onset of kidney microvascular outcomes (114.8 days; 95% CI, 58.1-176.4).
• Although renal outcomes improved, the time to death was shortened by 56.7 days in patients with elevated risk for kidney failure receiving intensive glycemic control.

IN PRACTICE:

“The observed effect of intensive glycemic control on kidney microvascular outcomes in ACCORD is almost entirely driven by a subset of patients representing one quarter of the trial eligible population at elevated risk for kidney failure at baseline,” the authors wrote.

SOURCE:

Vivek Charu of Stanford University School of Medicine, Stanford, California, led this study, which was published online on December 11, 2023, in the Journal of the American Society of Nephrology

LIMITATIONS:

The ACCORD study enrolled participants with a low risk for kidney disease. Therefore, this study lacks relevant data that might be needed to analyze the risks and benefits of intensive glycemic control in a population at high risk for kidney disease. Treatment options and monitoring approaches to glycemic control have evolved in the nearly 20 years since the ACCORD trial, which used insulin and sulfonylurea agents for glycemic control.

DISCLOSURES:

This work was supported by several grants secured by the authors. Some authors declared serving in advisory or leadership roles, receiving honoraria and research funding, and other ties with several sources.

A version of this article appeared on Medscape.com.

TOPLINE:

Patients with type 2 diabetes (T2D) at an elevated risk for kidney failure may stand to gain the most renal benefit with intensive glycemic control, but they also face the highest overall risk for death and hypoglycemic events.

METHODOLOGY:

• Studies show the primary benefit of intensive glycemic control in T2D is microvascular outcomes, mostly in the kidney, but no clear criteria exist to identify patients who may benefit most.
• Researchers conducted a post hoc analysis of the ACCORD trial, including 9777 patients with diabetes and cardiovascular disease or two or more cardiovascular risk factors.
• The 5-year kidney failure risk was estimated using the validated kidney failure risk equation (KFRE).
• The patients were randomly assigned to receive intensive glycemic control (A1c, < 6.0%) or standard glycemic control (A1c, 7.0%-7.9%).
• The primary outcomes were kidney microvascular events and all-cause mortality.

TAKEAWAY:

• Over a 7-year period, intensive vs standard glycemic control delayed the onset of kidney microvascular outcomes by 48.4 days (corresponding hazard ratio [HR], 0.75; 95% CI, 0.65-0.86) but reduced the time to death by 23.6 days (HR, 1.20; 95% CI, 1.04-1.40).
• Patients in the highest quartile of 5-year kidney failure risk according to KFRE benefited the most with intensive vs standard glycemic control and reported the longest delay in the onset of kidney microvascular outcomes (114.8 days; 95% CI, 58.1-176.4).
• Although renal outcomes improved, the time to death was shortened by 56.7 days in patients with elevated risk for kidney failure receiving intensive glycemic control.

IN PRACTICE:

“The observed effect of intensive glycemic control on kidney microvascular outcomes in ACCORD is almost entirely driven by a subset of patients representing one quarter of the trial eligible population at elevated risk for kidney failure at baseline,” the authors wrote.

SOURCE:

Vivek Charu of Stanford University School of Medicine, Stanford, California, led this study, which was published online on December 11, 2023, in the Journal of the American Society of Nephrology

LIMITATIONS:

The ACCORD study enrolled participants with a low risk for kidney disease. Therefore, this study lacks relevant data that might be needed to analyze the risks and benefits of intensive glycemic control in a population at high risk for kidney disease. Treatment options and monitoring approaches to glycemic control have evolved in the nearly 20 years since the ACCORD trial, which used insulin and sulfonylurea agents for glycemic control.

DISCLOSURES:

This work was supported by several grants secured by the authors. Some authors declared serving in advisory or leadership roles, receiving honoraria and research funding, and other ties with several sources.

A version of this article appeared on Medscape.com.

FAIRFAX, VIRGINIA — Pharmacologic treatment of gestational diabetes mellitus (GDM) remains challenged by overall poor trial quality, clinical practice guidelines that offer differing advice, and a limited ability to predict individual risk and treatment response, but researchers at the biennial meeting of the Diabetes in Pregnancy Study Group of North America expressed hope for more clarity in the near future and the ability to someday individualize treatment to account for what is increasingly viewed as a heterogeneous condition.

Until studies in 2015 and 2018 cast doubt on glyburide, “we used to have 80% [of our GDM patients] on glyburide, and 20% on insulin,” Maisa Feghali, MD, of the University of Pittsburgh, said during a discussion period. “Now we have 95% on insulin and 5% on oral hypoglycemics. I rely on insulin because I don’t have a better option, and I rely on research efforts [underway to provide better options]” in the future.

The American College of Obstetricians and Gynecologists recommends insulin as the preferred first-line pharmacologic therapy for GDM when pharmacologic therapy is needed, with metformin as an option when patients decline or cannot safely use insulin. Glyburide, ACOG said in its 2018 practice bulletin on GDM (Obstet Gynecol. 2018;131[2]:e49-64), should not be recommended as a first-line pharmacologic therapy.

The Society of Maternal-Fetal Medicine, on the other hand, has accepted metformin as a “reasonable and safe” first-line alternative to insulin — while recognizing that half of women will still require insulin to achieve glycemic control — and does not rule out consideration of glyburide. In its 2018 statement on the pharmacologic treatment of GDM, the society said that the evidence of benefit of one oral agent over another remains limited.  

“When you have dueling guidelines, it means the data are not that clear,” George Saade, MD, professor and chair of obstetrics and gynecology at the Eastern Virginia School of Medicine, Norfolk, said in a presentation on GDM. An upcoming $12 million multicenter study to be led by the Ohio State University College of Medicine — coined the DECIDE trial — should provide clarity, he said.

The trial, funded by the Patient-Centered Outcomes Research Institute, which funds comparative clinical effectiveness research designed to be broadly applicable to practice, will enroll and randomize over 1500 pregnant individuals with GDM to either oral metformin or insulin and will follow mothers and children until 2 years after delivery.

The study’s primary and secondary hypotheses, respectively, are that metformin is not inferior to insulin in reducing a composite adverse neonatal outcome (large for gestational age, neonatal hypoglycemia and/or hyperbilirubemia) and that metformin does not result in increased child body mass index at 2 years, compared with insulin. It will also look at patient-reported factors associated with metformin use compared to insulin use — factors that “are important ... to enable clinical implementation of study findings,” said Dr. Saade, who played a role in designing the study over the past several years.

The study will take a pragmatic, real-world approach by ensuring racial and ethnic, socioeconomic, urban and rural, and geographic diversity at both large academic and community-based sites across the United States.

The trial, to be led by Mark Landon, MD, and Kartik Venkatesh, MD, PhD, of Ohio State University, will be the first large trial in the United States to both directly compare the ability of oral hypoglycemics and insulin to prevent GDM-associated pregnancy complications, and to follow children for 2 years, Dr. Saade said. “Prior research was either outside the United States, not randomized, not adequately powered, or had no long-term child follow-up,” he added after the meeting.
 

The State Of Knowledge About Oral Hypoglycemics

The trial was envisioned several years ago as a three-arm comparative trial including the sulfonylurea glyburide, but data published in recent years has increasingly “not favored” glyburide, and many providers “have stopped using it,” Dr. Saade said during and after the meeting. At this point, “it would not be useful to include it” in a pragmatic trial, he said.

Glyburide became the number one agent after a seminal trial published in 2000 (N Engl J Med. 2000;343:1134-8) showed equivalent glycemic control in about 400 women with GDM who were randomized to receive insulin or glyburide. While the trial was not powered to evaluate other outcomes, there were no significant differences in neonatal complications.

In 2015, a large retrospective population-based study (JAMA Pediatr. 2015;169[5]:452-8) of more than 9,000 women with GDM showed higher risks of neonatal intensive care admission, neonatal hypoglycemia, and large-for-gestational age with glyburide compared with insulin. “It prompted a pause in thinking,” Dr. Saade recalled at the DPSG meeting. After that, several meta-analyses/systematic reviews compared the two treatments, showing varying and sometimes conflicting degrees of difference in neonatal outcomes.

In 2018, a French noninferiority randomized controlled trial (JAMA 2018;319[17]:1773-80) did not show that glyburide is not inferior to insulin in the prevention of perinatal outcomes (macrosomia, neonatal hypoglycemia, and hyperbilirubinemia). “If you add this trial to the systematic reviews, it would probably would shift more in favor of insulin,” Dr. Saade said, noting that the trial’s supplementary data included a higher rate of maternal hypoglycemia with glyburide. “I feel personally now, with all the data, that glyburide is inferior to insulin.”

A 2021 network meta-analysis (BMC Endocr Disord. 2021;21:199) that looked at glycemic control and neonatal outcomes in GDM treated with glyburide, metformin, or insulin, also offers valuable insight, Dr. Saade said. The meta-analysis used a Bayesian framework and presents results as a ranking estimated probability of a treatment being the best or worst — or in between — for different outcomes (glycemic control and neonatal outcomes), which “is one of the best ways to look at data these days,” he said.

“It tells us how likely [it is for one agent] to be better than others. Will it work most of the time? More than 60% of the time?” Dr. Saade explained. For example, the analysis “tell us that for large for gestational age, glyburide has a 94% chance of being the worst, metformin has an 80% change of being the best, and insulin a 76% chance of being in between.”

Overall, the 2021 analysis suggests that “glyburide is the most likely to be worst in most outcomes and that there is equipoise between metformin and insulin,” he said.

Meta-analyses of pharmacologic treatment of GDM have been challenged, he said, by inconsistent reporting in trials of GDM diagnostic criteria, severity of hyperglycemia, and small sample sizes (and wide confidence intervals). Criteria for supplemental insulin are also often “unclear” in trials, Dr. Saade said, as is involvement of social determinants of health and the “care package” enveloping pharmacologic interventions.

Dr. Saade, Dr. Landon, and other researchers have also lamented over the years that there is limited long-term follow-up of exposed offspring.
 

The Challenge of Heterogeneity

In another presentation on GDM, Maisa Feghali, MD, MS, emphasized that GDM is a heterogeneous condition, with clinical hyperglycemia not capturing individual variation in underlying physiologic processes. A 2016 study (Diabetes Care. 2016;39[6]:1052-5) assessing insulin sensitivity and secretion in 800-plus women at 24-30 weeks’ gestation found that about 50% of those with GDM had predominant insulin resistance, 30% had predominant insulin secretion deficit, and 20% were mixed.

Those with predominant insulin resistance had higher BMI, higher fasting glucose, larger infants, and greater risk of GDM-associated adverse outcomes, “suggesting that the risk is not universal or equivalent,” said Dr. Feghali, assistant professor in the department of obstetrics, gynecology and reproductive sciences at the University of Pittsburgh and the UPCM Magee-Women’s Hospital.

A 2019 multicenter European study (Diabetologia. 2019;62[11]:2118-28) found an even higher proportion of GDM involving predominant insulin resistance and, similarly, a greater risk of adverse pregnancy outcomes in these women than in insulin-sensitive women with GDM, “again suggesting that there’s probably some benefit to looking deeper at physiology to understand individual risk,” she said.

Research published decades ago showed that insulin sensitivity decreases by over 50% during pregnancy, and “what we’ve come to recognize is there [can be] insulin secretion deficiency that’s not able to surmount or overcome the insulin resistance that develops during advanced gestation,” she said. “We need to think not at the population level but at the individual level.”

Dr. Feghali is leading the MATCh-GDM (Metabolic Analysis for Treatment Choice in GDM) study, which has been randomizing women to receive either usual, unmatched treatment or treatment matched to GDM mechanism — metformin for predominant insulin resistance, glyburide, or insulin for predominant insulin secretion defects, and one of the three for combined mechanisms. Data are not available yet.

There is still more to be learned about the pharmacologic effects of oral hypoglycemics, she noted, pointing to a 2020 study (Clin Pharmacol Ther. 2020;107[6]:1362-72) that randomized women to glyburide, metformin, or glyburide/metformin combination therapy and measured insulin sensitivity, beta-cell responsivity, and disposition index. (The latter describes the overall metabolic state and is a product of insulin sensitivity and total beta-cell responsivity.)

“Somewhat surprisingly, they found metformin performed better than glyburide,” shifting the overall disposition index closer to normal, Dr. Feghali said. “But not surprisingly, they found the combination worked best.”

Total beta-cell responsivity occurred in 56% of the glyburide group and 74% of the combination group. Improvements in insulin sensitivity occurred in 84% of the metformin group and 74% of the combination group. Surprisingly, there was “a decrease in first-phase insulin secretion” with glyburide, noted Dr. Feghali — a finding that means “the glyburide story has turned out to be a little more complicated.” With metformin, there was a positive change in insulin secretion as well as insulin sensitivity.

The authors’ conclusion, she noted, “is that there’s potential in thinking about metformin first, as the primary treatment, and then adding glyburide after that.”
 

Future Use Of Incretin Mimetics, and Intensive Targets in Overweight/Obesity

Dr. Feghali wonders whether incretin hormone mimetics — such as glucagonlike peptide–1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) — could play a future role in GDM treatment, helping to increase insulin secretion.

She is currently recruiting for a pilot study on the pharmacokinetics and pharmacodynamics in GDM of exenatide, a FDA-approved GLP-1 agonist that has been shown not to cross the placenta and that should, research suggests, lower the risk of maternal hypoglycemia and limit the risk of excessive fetal growth, “overcoming some of the concerns we have with glyburide,” Dr. Feghali said.

A recent study of the gut-generated incretin response during an oral glucose tolerance test in pregnant women with and without GDM showed that post-load GLP-1 and GIP were higher in women with GDM, and that the GLP-1 secretion was associated with insulin secretion only in those with GDM (J Clin Endocrinol Metab. 2022;107(6):e2425-30). “In those with normal OGTT, insulin secretion was independent of GLP-1,” she said. “This study suggests there’s a potential role for incretin mimetics in GDM.”

Also regarding the individualization of GDM treatment, patients who are overweight or obese in the prepregnancy setting and have gestational diabetes represent a different phenotype, she noted, with higher fasting and postprandial blood glucose compared to normal-weight counterparts despite higher doses of medication.

“After controlling for gestational weight gain and glycemic control, we see there’s an independent effect of prepregnancy obesity specifically for an increased risk of macrosomia, preterm birth, and hypertensive disorders of pregnancy,” said Dr. Feghali, referring to a 2015 retrospective study of GDM and obesity (Obstet Gynecol. 2015;126:316-25). “It suggests that we might think about redrawing the line, not on diagnosis and screening but on treatment.”

The randomized, controlled Intensive Glycemic Targets in Overweight and Obese Women with Gestational Diabetes Mellitus (iGDM) trial, is now recruiting at multiple centers, including at Dr. Feghali’s University of Pittsburgh, and will investigate the effect of intensive glycemic targets (fasting < 90 mg/dL, 1-hour postprandial < 120 mg/dL) versus standard glycemic targets (fasting < 95 mg/dL, 1-hour postprandial < 140 mg/dL), she said.

In another presentation on GDM, Monica Longo, MD, PhD, of the Inova Health System in Fairfax, Va., said researchers are also looking at whether nutritional supplements such as myo-inositol can reduce the risk of adverse pregnancy outcomes in GDM, and whether probiotics can improve insulin sensitivity in some patients.

Data on newer insulin analogs in pregnancy are lacking, she noted. “Preliminary data has shown no malformations in infants, but there is some increase in hypoglycemia-related admissions to the NICU,” she said. “It’s worth it [to research more].”

FAIRFAX, VIRGINIA — Pharmacologic treatment of gestational diabetes mellitus (GDM) remains challenged by overall poor trial quality, clinical practice guidelines that offer differing advice, and a limited ability to predict individual risk and treatment response, but researchers at the biennial meeting of the Diabetes in Pregnancy Study Group of North America expressed hope for more clarity in the near future and the ability to someday individualize treatment to account for what is increasingly viewed as a heterogeneous condition.

Until studies in 2015 and 2018 cast doubt on glyburide, “we used to have 80% [of our GDM patients] on glyburide, and 20% on insulin,” Maisa Feghali, MD, of the University of Pittsburgh, said during a discussion period. “Now we have 95% on insulin and 5% on oral hypoglycemics. I rely on insulin because I don’t have a better option, and I rely on research efforts [underway to provide better options]” in the future.

The American College of Obstetricians and Gynecologists recommends insulin as the preferred first-line pharmacologic therapy for GDM when pharmacologic therapy is needed, with metformin as an option when patients decline or cannot safely use insulin. Glyburide, ACOG said in its 2018 practice bulletin on GDM (Obstet Gynecol. 2018;131[2]:e49-64), should not be recommended as a first-line pharmacologic therapy.

The Society of Maternal-Fetal Medicine, on the other hand, has accepted metformin as a “reasonable and safe” first-line alternative to insulin — while recognizing that half of women will still require insulin to achieve glycemic control — and does not rule out consideration of glyburide. In its 2018 statement on the pharmacologic treatment of GDM, the society said that the evidence of benefit of one oral agent over another remains limited.  

“When you have dueling guidelines, it means the data are not that clear,” George Saade, MD, professor and chair of obstetrics and gynecology at the Eastern Virginia School of Medicine, Norfolk, said in a presentation on GDM. An upcoming $12 million multicenter study to be led by the Ohio State University College of Medicine — coined the DECIDE trial — should provide clarity, he said.

The trial, funded by the Patient-Centered Outcomes Research Institute, which funds comparative clinical effectiveness research designed to be broadly applicable to practice, will enroll and randomize over 1500 pregnant individuals with GDM to either oral metformin or insulin and will follow mothers and children until 2 years after delivery.

The study’s primary and secondary hypotheses, respectively, are that metformin is not inferior to insulin in reducing a composite adverse neonatal outcome (large for gestational age, neonatal hypoglycemia and/or hyperbilirubemia) and that metformin does not result in increased child body mass index at 2 years, compared with insulin. It will also look at patient-reported factors associated with metformin use compared to insulin use — factors that “are important ... to enable clinical implementation of study findings,” said Dr. Saade, who played a role in designing the study over the past several years.

The study will take a pragmatic, real-world approach by ensuring racial and ethnic, socioeconomic, urban and rural, and geographic diversity at both large academic and community-based sites across the United States.

The trial, to be led by Mark Landon, MD, and Kartik Venkatesh, MD, PhD, of Ohio State University, will be the first large trial in the United States to both directly compare the ability of oral hypoglycemics and insulin to prevent GDM-associated pregnancy complications, and to follow children for 2 years, Dr. Saade said. “Prior research was either outside the United States, not randomized, not adequately powered, or had no long-term child follow-up,” he added after the meeting.
 

The State Of Knowledge About Oral Hypoglycemics

The trial was envisioned several years ago as a three-arm comparative trial including the sulfonylurea glyburide, but data published in recent years has increasingly “not favored” glyburide, and many providers “have stopped using it,” Dr. Saade said during and after the meeting. At this point, “it would not be useful to include it” in a pragmatic trial, he said.

Glyburide became the number one agent after a seminal trial published in 2000 (N Engl J Med. 2000;343:1134-8) showed equivalent glycemic control in about 400 women with GDM who were randomized to receive insulin or glyburide. While the trial was not powered to evaluate other outcomes, there were no significant differences in neonatal complications.

In 2015, a large retrospective population-based study (JAMA Pediatr. 2015;169[5]:452-8) of more than 9,000 women with GDM showed higher risks of neonatal intensive care admission, neonatal hypoglycemia, and large-for-gestational age with glyburide compared with insulin. “It prompted a pause in thinking,” Dr. Saade recalled at the DPSG meeting. After that, several meta-analyses/systematic reviews compared the two treatments, showing varying and sometimes conflicting degrees of difference in neonatal outcomes.

In 2018, a French noninferiority randomized controlled trial (JAMA 2018;319[17]:1773-80) did not show that glyburide is not inferior to insulin in the prevention of perinatal outcomes (macrosomia, neonatal hypoglycemia, and hyperbilirubinemia). “If you add this trial to the systematic reviews, it would probably would shift more in favor of insulin,” Dr. Saade said, noting that the trial’s supplementary data included a higher rate of maternal hypoglycemia with glyburide. “I feel personally now, with all the data, that glyburide is inferior to insulin.”

A 2021 network meta-analysis (BMC Endocr Disord. 2021;21:199) that looked at glycemic control and neonatal outcomes in GDM treated with glyburide, metformin, or insulin, also offers valuable insight, Dr. Saade said. The meta-analysis used a Bayesian framework and presents results as a ranking estimated probability of a treatment being the best or worst — or in between — for different outcomes (glycemic control and neonatal outcomes), which “is one of the best ways to look at data these days,” he said.

“It tells us how likely [it is for one agent] to be better than others. Will it work most of the time? More than 60% of the time?” Dr. Saade explained. For example, the analysis “tell us that for large for gestational age, glyburide has a 94% chance of being the worst, metformin has an 80% change of being the best, and insulin a 76% chance of being in between.”

Overall, the 2021 analysis suggests that “glyburide is the most likely to be worst in most outcomes and that there is equipoise between metformin and insulin,” he said.

Meta-analyses of pharmacologic treatment of GDM have been challenged, he said, by inconsistent reporting in trials of GDM diagnostic criteria, severity of hyperglycemia, and small sample sizes (and wide confidence intervals). Criteria for supplemental insulin are also often “unclear” in trials, Dr. Saade said, as is involvement of social determinants of health and the “care package” enveloping pharmacologic interventions.

Dr. Saade, Dr. Landon, and other researchers have also lamented over the years that there is limited long-term follow-up of exposed offspring.
 

The Challenge of Heterogeneity

In another presentation on GDM, Maisa Feghali, MD, MS, emphasized that GDM is a heterogeneous condition, with clinical hyperglycemia not capturing individual variation in underlying physiologic processes. A 2016 study (Diabetes Care. 2016;39[6]:1052-5) assessing insulin sensitivity and secretion in 800-plus women at 24-30 weeks’ gestation found that about 50% of those with GDM had predominant insulin resistance, 30% had predominant insulin secretion deficit, and 20% were mixed.

Those with predominant insulin resistance had higher BMI, higher fasting glucose, larger infants, and greater risk of GDM-associated adverse outcomes, “suggesting that the risk is not universal or equivalent,” said Dr. Feghali, assistant professor in the department of obstetrics, gynecology and reproductive sciences at the University of Pittsburgh and the UPCM Magee-Women’s Hospital.

A 2019 multicenter European study (Diabetologia. 2019;62[11]:2118-28) found an even higher proportion of GDM involving predominant insulin resistance and, similarly, a greater risk of adverse pregnancy outcomes in these women than in insulin-sensitive women with GDM, “again suggesting that there’s probably some benefit to looking deeper at physiology to understand individual risk,” she said.

Research published decades ago showed that insulin sensitivity decreases by over 50% during pregnancy, and “what we’ve come to recognize is there [can be] insulin secretion deficiency that’s not able to surmount or overcome the insulin resistance that develops during advanced gestation,” she said. “We need to think not at the population level but at the individual level.”

Dr. Feghali is leading the MATCh-GDM (Metabolic Analysis for Treatment Choice in GDM) study, which has been randomizing women to receive either usual, unmatched treatment or treatment matched to GDM mechanism — metformin for predominant insulin resistance, glyburide, or insulin for predominant insulin secretion defects, and one of the three for combined mechanisms. Data are not available yet.

There is still more to be learned about the pharmacologic effects of oral hypoglycemics, she noted, pointing to a 2020 study (Clin Pharmacol Ther. 2020;107[6]:1362-72) that randomized women to glyburide, metformin, or glyburide/metformin combination therapy and measured insulin sensitivity, beta-cell responsivity, and disposition index. (The latter describes the overall metabolic state and is a product of insulin sensitivity and total beta-cell responsivity.)

“Somewhat surprisingly, they found metformin performed better than glyburide,” shifting the overall disposition index closer to normal, Dr. Feghali said. “But not surprisingly, they found the combination worked best.”

Total beta-cell responsivity occurred in 56% of the glyburide group and 74% of the combination group. Improvements in insulin sensitivity occurred in 84% of the metformin group and 74% of the combination group. Surprisingly, there was “a decrease in first-phase insulin secretion” with glyburide, noted Dr. Feghali — a finding that means “the glyburide story has turned out to be a little more complicated.” With metformin, there was a positive change in insulin secretion as well as insulin sensitivity.

The authors’ conclusion, she noted, “is that there’s potential in thinking about metformin first, as the primary treatment, and then adding glyburide after that.”
 

Future Use Of Incretin Mimetics, and Intensive Targets in Overweight/Obesity

Dr. Feghali wonders whether incretin hormone mimetics — such as glucagonlike peptide–1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) — could play a future role in GDM treatment, helping to increase insulin secretion.

She is currently recruiting for a pilot study on the pharmacokinetics and pharmacodynamics in GDM of exenatide, a FDA-approved GLP-1 agonist that has been shown not to cross the placenta and that should, research suggests, lower the risk of maternal hypoglycemia and limit the risk of excessive fetal growth, “overcoming some of the concerns we have with glyburide,” Dr. Feghali said.

A recent study of the gut-generated incretin response during an oral glucose tolerance test in pregnant women with and without GDM showed that post-load GLP-1 and GIP were higher in women with GDM, and that the GLP-1 secretion was associated with insulin secretion only in those with GDM (J Clin Endocrinol Metab. 2022;107(6):e2425-30). “In those with normal OGTT, insulin secretion was independent of GLP-1,” she said. “This study suggests there’s a potential role for incretin mimetics in GDM.”

Also regarding the individualization of GDM treatment, patients who are overweight or obese in the prepregnancy setting and have gestational diabetes represent a different phenotype, she noted, with higher fasting and postprandial blood glucose compared to normal-weight counterparts despite higher doses of medication.

“After controlling for gestational weight gain and glycemic control, we see there’s an independent effect of prepregnancy obesity specifically for an increased risk of macrosomia, preterm birth, and hypertensive disorders of pregnancy,” said Dr. Feghali, referring to a 2015 retrospective study of GDM and obesity (Obstet Gynecol. 2015;126:316-25). “It suggests that we might think about redrawing the line, not on diagnosis and screening but on treatment.”

The randomized, controlled Intensive Glycemic Targets in Overweight and Obese Women with Gestational Diabetes Mellitus (iGDM) trial, is now recruiting at multiple centers, including at Dr. Feghali’s University of Pittsburgh, and will investigate the effect of intensive glycemic targets (fasting < 90 mg/dL, 1-hour postprandial < 120 mg/dL) versus standard glycemic targets (fasting < 95 mg/dL, 1-hour postprandial < 140 mg/dL), she said.

In another presentation on GDM, Monica Longo, MD, PhD, of the Inova Health System in Fairfax, Va., said researchers are also looking at whether nutritional supplements such as myo-inositol can reduce the risk of adverse pregnancy outcomes in GDM, and whether probiotics can improve insulin sensitivity in some patients.

Data on newer insulin analogs in pregnancy are lacking, she noted. “Preliminary data has shown no malformations in infants, but there is some increase in hypoglycemia-related admissions to the NICU,” she said. “It’s worth it [to research more].”

FAIRFAX, VIRGINIA — Pharmacologic treatment of gestational diabetes mellitus (GDM) remains challenged by overall poor trial quality, clinical practice guidelines that offer differing advice, and a limited ability to predict individual risk and treatment response, but researchers at the biennial meeting of the Diabetes in Pregnancy Study Group of North America expressed hope for more clarity in the near future and the ability to someday individualize treatment to account for what is increasingly viewed as a heterogeneous condition.

Until studies in 2015 and 2018 cast doubt on glyburide, “we used to have 80% [of our GDM patients] on glyburide, and 20% on insulin,” Maisa Feghali, MD, of the University of Pittsburgh, said during a discussion period. “Now we have 95% on insulin and 5% on oral hypoglycemics. I rely on insulin because I don’t have a better option, and I rely on research efforts [underway to provide better options]” in the future.

The American College of Obstetricians and Gynecologists recommends insulin as the preferred first-line pharmacologic therapy for GDM when pharmacologic therapy is needed, with metformin as an option when patients decline or cannot safely use insulin. Glyburide, ACOG said in its 2018 practice bulletin on GDM (Obstet Gynecol. 2018;131[2]:e49-64), should not be recommended as a first-line pharmacologic therapy.

The Society of Maternal-Fetal Medicine, on the other hand, has accepted metformin as a “reasonable and safe” first-line alternative to insulin — while recognizing that half of women will still require insulin to achieve glycemic control — and does not rule out consideration of glyburide. In its 2018 statement on the pharmacologic treatment of GDM, the society said that the evidence of benefit of one oral agent over another remains limited.  

“When you have dueling guidelines, it means the data are not that clear,” George Saade, MD, professor and chair of obstetrics and gynecology at the Eastern Virginia School of Medicine, Norfolk, said in a presentation on GDM. An upcoming $12 million multicenter study to be led by the Ohio State University College of Medicine — coined the DECIDE trial — should provide clarity, he said.

The trial, funded by the Patient-Centered Outcomes Research Institute, which funds comparative clinical effectiveness research designed to be broadly applicable to practice, will enroll and randomize over 1500 pregnant individuals with GDM to either oral metformin or insulin and will follow mothers and children until 2 years after delivery.

The study’s primary and secondary hypotheses, respectively, are that metformin is not inferior to insulin in reducing a composite adverse neonatal outcome (large for gestational age, neonatal hypoglycemia and/or hyperbilirubemia) and that metformin does not result in increased child body mass index at 2 years, compared with insulin. It will also look at patient-reported factors associated with metformin use compared to insulin use — factors that “are important ... to enable clinical implementation of study findings,” said Dr. Saade, who played a role in designing the study over the past several years.

The study will take a pragmatic, real-world approach by ensuring racial and ethnic, socioeconomic, urban and rural, and geographic diversity at both large academic and community-based sites across the United States.

The trial, to be led by Mark Landon, MD, and Kartik Venkatesh, MD, PhD, of Ohio State University, will be the first large trial in the United States to both directly compare the ability of oral hypoglycemics and insulin to prevent GDM-associated pregnancy complications, and to follow children for 2 years, Dr. Saade said. “Prior research was either outside the United States, not randomized, not adequately powered, or had no long-term child follow-up,” he added after the meeting.
 

The State Of Knowledge About Oral Hypoglycemics

The trial was envisioned several years ago as a three-arm comparative trial including the sulfonylurea glyburide, but data published in recent years has increasingly “not favored” glyburide, and many providers “have stopped using it,” Dr. Saade said during and after the meeting. At this point, “it would not be useful to include it” in a pragmatic trial, he said.

Glyburide became the number one agent after a seminal trial published in 2000 (N Engl J Med. 2000;343:1134-8) showed equivalent glycemic control in about 400 women with GDM who were randomized to receive insulin or glyburide. While the trial was not powered to evaluate other outcomes, there were no significant differences in neonatal complications.

In 2015, a large retrospective population-based study (JAMA Pediatr. 2015;169[5]:452-8) of more than 9,000 women with GDM showed higher risks of neonatal intensive care admission, neonatal hypoglycemia, and large-for-gestational age with glyburide compared with insulin. “It prompted a pause in thinking,” Dr. Saade recalled at the DPSG meeting. After that, several meta-analyses/systematic reviews compared the two treatments, showing varying and sometimes conflicting degrees of difference in neonatal outcomes.

In 2018, a French noninferiority randomized controlled trial (JAMA 2018;319[17]:1773-80) did not show that glyburide is not inferior to insulin in the prevention of perinatal outcomes (macrosomia, neonatal hypoglycemia, and hyperbilirubinemia). “If you add this trial to the systematic reviews, it would probably would shift more in favor of insulin,” Dr. Saade said, noting that the trial’s supplementary data included a higher rate of maternal hypoglycemia with glyburide. “I feel personally now, with all the data, that glyburide is inferior to insulin.”

A 2021 network meta-analysis (BMC Endocr Disord. 2021;21:199) that looked at glycemic control and neonatal outcomes in GDM treated with glyburide, metformin, or insulin, also offers valuable insight, Dr. Saade said. The meta-analysis used a Bayesian framework and presents results as a ranking estimated probability of a treatment being the best or worst — or in between — for different outcomes (glycemic control and neonatal outcomes), which “is one of the best ways to look at data these days,” he said.

“It tells us how likely [it is for one agent] to be better than others. Will it work most of the time? More than 60% of the time?” Dr. Saade explained. For example, the analysis “tell us that for large for gestational age, glyburide has a 94% chance of being the worst, metformin has an 80% change of being the best, and insulin a 76% chance of being in between.”

Overall, the 2021 analysis suggests that “glyburide is the most likely to be worst in most outcomes and that there is equipoise between metformin and insulin,” he said.

Meta-analyses of pharmacologic treatment of GDM have been challenged, he said, by inconsistent reporting in trials of GDM diagnostic criteria, severity of hyperglycemia, and small sample sizes (and wide confidence intervals). Criteria for supplemental insulin are also often “unclear” in trials, Dr. Saade said, as is involvement of social determinants of health and the “care package” enveloping pharmacologic interventions.

Dr. Saade, Dr. Landon, and other researchers have also lamented over the years that there is limited long-term follow-up of exposed offspring.
 

The Challenge of Heterogeneity

In another presentation on GDM, Maisa Feghali, MD, MS, emphasized that GDM is a heterogeneous condition, with clinical hyperglycemia not capturing individual variation in underlying physiologic processes. A 2016 study (Diabetes Care. 2016;39[6]:1052-5) assessing insulin sensitivity and secretion in 800-plus women at 24-30 weeks’ gestation found that about 50% of those with GDM had predominant insulin resistance, 30% had predominant insulin secretion deficit, and 20% were mixed.

Those with predominant insulin resistance had higher BMI, higher fasting glucose, larger infants, and greater risk of GDM-associated adverse outcomes, “suggesting that the risk is not universal or equivalent,” said Dr. Feghali, assistant professor in the department of obstetrics, gynecology and reproductive sciences at the University of Pittsburgh and the UPCM Magee-Women’s Hospital.

A 2019 multicenter European study (Diabetologia. 2019;62[11]:2118-28) found an even higher proportion of GDM involving predominant insulin resistance and, similarly, a greater risk of adverse pregnancy outcomes in these women than in insulin-sensitive women with GDM, “again suggesting that there’s probably some benefit to looking deeper at physiology to understand individual risk,” she said.

Research published decades ago showed that insulin sensitivity decreases by over 50% during pregnancy, and “what we’ve come to recognize is there [can be] insulin secretion deficiency that’s not able to surmount or overcome the insulin resistance that develops during advanced gestation,” she said. “We need to think not at the population level but at the individual level.”

Dr. Feghali is leading the MATCh-GDM (Metabolic Analysis for Treatment Choice in GDM) study, which has been randomizing women to receive either usual, unmatched treatment or treatment matched to GDM mechanism — metformin for predominant insulin resistance, glyburide, or insulin for predominant insulin secretion defects, and one of the three for combined mechanisms. Data are not available yet.

There is still more to be learned about the pharmacologic effects of oral hypoglycemics, she noted, pointing to a 2020 study (Clin Pharmacol Ther. 2020;107[6]:1362-72) that randomized women to glyburide, metformin, or glyburide/metformin combination therapy and measured insulin sensitivity, beta-cell responsivity, and disposition index. (The latter describes the overall metabolic state and is a product of insulin sensitivity and total beta-cell responsivity.)

“Somewhat surprisingly, they found metformin performed better than glyburide,” shifting the overall disposition index closer to normal, Dr. Feghali said. “But not surprisingly, they found the combination worked best.”

Total beta-cell responsivity occurred in 56% of the glyburide group and 74% of the combination group. Improvements in insulin sensitivity occurred in 84% of the metformin group and 74% of the combination group. Surprisingly, there was “a decrease in first-phase insulin secretion” with glyburide, noted Dr. Feghali — a finding that means “the glyburide story has turned out to be a little more complicated.” With metformin, there was a positive change in insulin secretion as well as insulin sensitivity.

The authors’ conclusion, she noted, “is that there’s potential in thinking about metformin first, as the primary treatment, and then adding glyburide after that.”
 

Future Use Of Incretin Mimetics, and Intensive Targets in Overweight/Obesity

Dr. Feghali wonders whether incretin hormone mimetics — such as glucagonlike peptide–1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) — could play a future role in GDM treatment, helping to increase insulin secretion.

She is currently recruiting for a pilot study on the pharmacokinetics and pharmacodynamics in GDM of exenatide, a FDA-approved GLP-1 agonist that has been shown not to cross the placenta and that should, research suggests, lower the risk of maternal hypoglycemia and limit the risk of excessive fetal growth, “overcoming some of the concerns we have with glyburide,” Dr. Feghali said.

A recent study of the gut-generated incretin response during an oral glucose tolerance test in pregnant women with and without GDM showed that post-load GLP-1 and GIP were higher in women with GDM, and that the GLP-1 secretion was associated with insulin secretion only in those with GDM (J Clin Endocrinol Metab. 2022;107(6):e2425-30). “In those with normal OGTT, insulin secretion was independent of GLP-1,” she said. “This study suggests there’s a potential role for incretin mimetics in GDM.”

Also regarding the individualization of GDM treatment, patients who are overweight or obese in the prepregnancy setting and have gestational diabetes represent a different phenotype, she noted, with higher fasting and postprandial blood glucose compared to normal-weight counterparts despite higher doses of medication.

“After controlling for gestational weight gain and glycemic control, we see there’s an independent effect of prepregnancy obesity specifically for an increased risk of macrosomia, preterm birth, and hypertensive disorders of pregnancy,” said Dr. Feghali, referring to a 2015 retrospective study of GDM and obesity (Obstet Gynecol. 2015;126:316-25). “It suggests that we might think about redrawing the line, not on diagnosis and screening but on treatment.”

The randomized, controlled Intensive Glycemic Targets in Overweight and Obese Women with Gestational Diabetes Mellitus (iGDM) trial, is now recruiting at multiple centers, including at Dr. Feghali’s University of Pittsburgh, and will investigate the effect of intensive glycemic targets (fasting < 90 mg/dL, 1-hour postprandial < 120 mg/dL) versus standard glycemic targets (fasting < 95 mg/dL, 1-hour postprandial < 140 mg/dL), she said.

In another presentation on GDM, Monica Longo, MD, PhD, of the Inova Health System in Fairfax, Va., said researchers are also looking at whether nutritional supplements such as myo-inositol can reduce the risk of adverse pregnancy outcomes in GDM, and whether probiotics can improve insulin sensitivity in some patients.

Data on newer insulin analogs in pregnancy are lacking, she noted. “Preliminary data has shown no malformations in infants, but there is some increase in hypoglycemia-related admissions to the NICU,” she said. “It’s worth it [to research more].”

Infection with COVID-19 conferred a nearly twofold risk of developing alopecia areata (AA), results from a large analysis of Korean patients demonstrated.

“There is a growing number of reports on new onset, exacerbation, and recurrence of AA after COVID-19,” corresponding author Jin Park, MD, PhD, of the department of dermatology at Jeonbuk National University Medical School, South Korea, and colleagues wrote in a research letter published online January 10, 2024, in JAMA Dermatology. “However, evidence supporting an association between COVID-19 and AA is limited.”

To investigate the association between COVID-19 and AA, the researchers used data from the Korea Disease Control and Prevention Agency–COVID-19–National Health Insurance Service cohort to conduct a propensity score–matched, nationwide, population-based cohort study from October 8, 2020, to September 30, 2021. They used Cox proportional hazards regression to calculate the incidence, prevalence, and adjusted hazard ratios (AHRs) for AA.

The cohort consisted of 259,369 patients with COVID-19 and 259,369 uninfected controls. The researchers observed an increased risk of telogen effluvium in patients with COVID-19 compared with the uninfected controls (AHR, 6.40; 95% CI, 4.92-8.33), while the incidence of epidermal cysts, benign skin tumors, and other negative control outcomes did not differ between groups.

Meanwhile, the incidence of AA in patients with COVID-19 was significantly higher compared with the uninfected controls (43.19 per 10,000 person-years [PY]), regardless of clinical subtype. This translated into an AHR of 1.82 (95% CI, 1.60-2.07). In other findings, the incidence of patchy AA and alopecia totalis and alopecia universalis (AT/AU) was 35.94 and 7.24 per 10,000 PY in patients with COVID-19 compared with 19.43 and 4.18 per 10,000 PY in uninfected controls, respectively.

“These findings support the possible role of COVID-19 in AA occurrence and exacerbation, although other environmental factors, such as psychological stress, may have also contributed to AA development during the pandemic,” the authors concluded. “Plausible mechanisms of AA following COVID-19 include antigenic molecular mimicry between SARS-CoV-2 and hair follicle autoantigens, cytokine shifting, and bystander activation.”

They acknowledged certain limitations of the analysis, including the potential for detection or misclassification bias and the fact that it did not evaluate causality between the two conditions.

Shari Lipner, MD, PhD, associate professor of dermatology at Weill Cornell Medicine, New York, who was asked to comment on the study, said that strengths of the study include the large sample size, and the use of positive and negative outcome controls, and that the incidence and prevalence of AA in Korea was stable during the prepandemic period. “A weakness of the study is that all alopecia areata cases may not have necessarily been confirmed,” Dr. Lipner told this news organization.

“Based on this study, dermatologists may consider AA in the differential diagnosis for a patient presenting with hair loss with recent COVID-19 diagnosis,” she added, noting that the potential for prevention of AA flares is also a reason to recommend COVID-19 vaccination for patients with a history of AA.

Christine Ko, MD, professor of dermatology and pathology at Yale University, New Haven, Connecticut, who was also asked to comment on the study, said that while the analysis suggests a definite epidemiologic association between COVID-19 and AA, “any causal relationship needs further study.” She added that she has no specific advice for patients who develop AA following a COVID-19 infection. “Any conversation about AA can be difficult because there is no way to prognosticate if someone will just have one small, localized area of hair loss,” or several small areas, versus loss of all hair on the head or even the body as well, Dr. Ko explained.

The study was supported with grants from the National Research Foundation of the Korean Government and the Ministry of Health and Welfare, Republic of Korea. The authors, as well as Dr. Lipner and Dr. Ko, reported having no relevant disclosures.

Infection with COVID-19 conferred a nearly twofold risk of developing alopecia areata (AA), results from a large analysis of Korean patients demonstrated.

“There is a growing number of reports on new onset, exacerbation, and recurrence of AA after COVID-19,” corresponding author Jin Park, MD, PhD, of the department of dermatology at Jeonbuk National University Medical School, South Korea, and colleagues wrote in a research letter published online January 10, 2024, in JAMA Dermatology. “However, evidence supporting an association between COVID-19 and AA is limited.”

To investigate the association between COVID-19 and AA, the researchers used data from the Korea Disease Control and Prevention Agency–COVID-19–National Health Insurance Service cohort to conduct a propensity score–matched, nationwide, population-based cohort study from October 8, 2020, to September 30, 2021. They used Cox proportional hazards regression to calculate the incidence, prevalence, and adjusted hazard ratios (AHRs) for AA.

The cohort consisted of 259,369 patients with COVID-19 and 259,369 uninfected controls. The researchers observed an increased risk of telogen effluvium in patients with COVID-19 compared with the uninfected controls (AHR, 6.40; 95% CI, 4.92-8.33), while the incidence of epidermal cysts, benign skin tumors, and other negative control outcomes did not differ between groups.

Meanwhile, the incidence of AA in patients with COVID-19 was significantly higher compared with the uninfected controls (43.19 per 10,000 person-years [PY]), regardless of clinical subtype. This translated into an AHR of 1.82 (95% CI, 1.60-2.07). In other findings, the incidence of patchy AA and alopecia totalis and alopecia universalis (AT/AU) was 35.94 and 7.24 per 10,000 PY in patients with COVID-19 compared with 19.43 and 4.18 per 10,000 PY in uninfected controls, respectively.

“These findings support the possible role of COVID-19 in AA occurrence and exacerbation, although other environmental factors, such as psychological stress, may have also contributed to AA development during the pandemic,” the authors concluded. “Plausible mechanisms of AA following COVID-19 include antigenic molecular mimicry between SARS-CoV-2 and hair follicle autoantigens, cytokine shifting, and bystander activation.”

They acknowledged certain limitations of the analysis, including the potential for detection or misclassification bias and the fact that it did not evaluate causality between the two conditions.

Shari Lipner, MD, PhD, associate professor of dermatology at Weill Cornell Medicine, New York, who was asked to comment on the study, said that strengths of the study include the large sample size, and the use of positive and negative outcome controls, and that the incidence and prevalence of AA in Korea was stable during the prepandemic period. “A weakness of the study is that all alopecia areata cases may not have necessarily been confirmed,” Dr. Lipner told this news organization.

“Based on this study, dermatologists may consider AA in the differential diagnosis for a patient presenting with hair loss with recent COVID-19 diagnosis,” she added, noting that the potential for prevention of AA flares is also a reason to recommend COVID-19 vaccination for patients with a history of AA.

Christine Ko, MD, professor of dermatology and pathology at Yale University, New Haven, Connecticut, who was also asked to comment on the study, said that while the analysis suggests a definite epidemiologic association between COVID-19 and AA, “any causal relationship needs further study.” She added that she has no specific advice for patients who develop AA following a COVID-19 infection. “Any conversation about AA can be difficult because there is no way to prognosticate if someone will just have one small, localized area of hair loss,” or several small areas, versus loss of all hair on the head or even the body as well, Dr. Ko explained.

The study was supported with grants from the National Research Foundation of the Korean Government and the Ministry of Health and Welfare, Republic of Korea. The authors, as well as Dr. Lipner and Dr. Ko, reported having no relevant disclosures.

Infection with COVID-19 conferred a nearly twofold risk of developing alopecia areata (AA), results from a large analysis of Korean patients demonstrated.

“There is a growing number of reports on new onset, exacerbation, and recurrence of AA after COVID-19,” corresponding author Jin Park, MD, PhD, of the department of dermatology at Jeonbuk National University Medical School, South Korea, and colleagues wrote in a research letter published online January 10, 2024, in JAMA Dermatology. “However, evidence supporting an association between COVID-19 and AA is limited.”

To investigate the association between COVID-19 and AA, the researchers used data from the Korea Disease Control and Prevention Agency–COVID-19–National Health Insurance Service cohort to conduct a propensity score–matched, nationwide, population-based cohort study from October 8, 2020, to September 30, 2021. They used Cox proportional hazards regression to calculate the incidence, prevalence, and adjusted hazard ratios (AHRs) for AA.

The cohort consisted of 259,369 patients with COVID-19 and 259,369 uninfected controls. The researchers observed an increased risk of telogen effluvium in patients with COVID-19 compared with the uninfected controls (AHR, 6.40; 95% CI, 4.92-8.33), while the incidence of epidermal cysts, benign skin tumors, and other negative control outcomes did not differ between groups.

Meanwhile, the incidence of AA in patients with COVID-19 was significantly higher compared with the uninfected controls (43.19 per 10,000 person-years [PY]), regardless of clinical subtype. This translated into an AHR of 1.82 (95% CI, 1.60-2.07). In other findings, the incidence of patchy AA and alopecia totalis and alopecia universalis (AT/AU) was 35.94 and 7.24 per 10,000 PY in patients with COVID-19 compared with 19.43 and 4.18 per 10,000 PY in uninfected controls, respectively.

“These findings support the possible role of COVID-19 in AA occurrence and exacerbation, although other environmental factors, such as psychological stress, may have also contributed to AA development during the pandemic,” the authors concluded. “Plausible mechanisms of AA following COVID-19 include antigenic molecular mimicry between SARS-CoV-2 and hair follicle autoantigens, cytokine shifting, and bystander activation.”

They acknowledged certain limitations of the analysis, including the potential for detection or misclassification bias and the fact that it did not evaluate causality between the two conditions.

Shari Lipner, MD, PhD, associate professor of dermatology at Weill Cornell Medicine, New York, who was asked to comment on the study, said that strengths of the study include the large sample size, and the use of positive and negative outcome controls, and that the incidence and prevalence of AA in Korea was stable during the prepandemic period. “A weakness of the study is that all alopecia areata cases may not have necessarily been confirmed,” Dr. Lipner told this news organization.

“Based on this study, dermatologists may consider AA in the differential diagnosis for a patient presenting with hair loss with recent COVID-19 diagnosis,” she added, noting that the potential for prevention of AA flares is also a reason to recommend COVID-19 vaccination for patients with a history of AA.

Christine Ko, MD, professor of dermatology and pathology at Yale University, New Haven, Connecticut, who was also asked to comment on the study, said that while the analysis suggests a definite epidemiologic association between COVID-19 and AA, “any causal relationship needs further study.” She added that she has no specific advice for patients who develop AA following a COVID-19 infection. “Any conversation about AA can be difficult because there is no way to prognosticate if someone will just have one small, localized area of hair loss,” or several small areas, versus loss of all hair on the head or even the body as well, Dr. Ko explained.

The study was supported with grants from the National Research Foundation of the Korean Government and the Ministry of Health and Welfare, Republic of Korea. The authors, as well as Dr. Lipner and Dr. Ko, reported having no relevant disclosures.

Exposure to endocrine-disrupting chemicals (EDCs) via daily use of plastics is a major contributor to the overall disease burden in the United States and the associated costs to society amount to more than 1% of the gross domestic product, revealed a large-scale analysis.

The research, published in the Journal of the Endocrine Society, indicated that taken together, the disease burden attributable to EDCs used in the manufacture of plastics added up to almost $250 billion in 2018 alone.

“The diseases due to plastics run the entire life course from preterm birth to obesity, heart disease, and cancers,” commented lead author Leonardo Trasande, MD, MPP, Jim G. Hendrick, MD Professor of Pediatrics, Department of Pediatrics, NYU Langone Medical Center, New York, in a release.

“Our study drives home the need to address chemicals used in plastic materials” through global treaties and other policy initiatives, he said, so as to “reduce these costs” in line with reductions in exposure to the chemicals.

Co-author Michael Belliveau, Executive Director at Defend Our Health in Portland, ME, agreed, saying: “We can reduce these health costs and the prevalence of chronic endocrine diseases such as diabetes and obesity if governments and companies enact policies that minimize exposure to EDCs to protect public health and the environment.”

Plastics may contain any one of a number of EDCs, such as polybrominated diphenylethers in flame retardant additives, phthalates in food packaging, bisphenols in can linings, and perfluoroalkyl and polyfluoroalkyl substances (PFAS) in nonstick cooking utensils.

These chemicals have been shown to leach and disturb the body’s hormone systems, increasing the risk for cancer, diabetes, reproductive disorders, neurological impairments in developing fetuses and children, and even death.

In March 2022, the United Nations Environment Assembly committed to a global plastics treaty to “end plastic pollution and forge an international legally binding agreement by 2024” that “addresses the full life cycle of plastic, including its production, design and disposal.”

Minimizing EDC Exposure

But what can doctors tell their patients today to help them reduce their exposure to EDCs?

“There are safe and simple steps that people can take to limit their exposure to the chemicals of greatest concern,” Dr. Trasande told this news organization.

This can be partly achieved by reducing plastic use down to its essentials. “To use an example, when you are flying, fill up a stainless steel container after clearing security. At home, use glass or stainless steel” rather than plastic bottles or containers.

In particular, “avoiding microwaving plastic is important,” Dr. Trasande said, “even if a container says it’s microwave-safe.”

He warned that “many chemicals used in plastic are not covalently bound, and heat facilitates leaching into food. Microscopic contaminants can also get into food when you microwave plastic.”

Dr. Trasande also suggests limiting canned food consumption and avoiding cleaning plastic food containers in machine dishwashers.

Calculating the Disease Burden

To accurately assess the “the tradeoffs involved in the ongoing reliance on plastic production as a source of economic productivity,” the current researchers calculated the attributable disease burden and cost related to EDCs used in plastic materials in the United States in 2018.

Building on previously published analyses, they used industry reports, publications by national and international governing bodies, and peer-reviewed publications to determine the usage of each type of EDC and its attributable disease and disability burden.

This plastic-related fraction (PRF) of disease burden was then used to calculate an updated cost estimate for each EDC, based on the assumption that the disease burden is directly proportional to its exposure.

They found that for bisphenol A, 97.5% of its use, and therefore its estimated PRF of disease burden, was related to the manufacture of plastics, while this figure was 98%-100% for phthalates. For PDBE, 98% of its use was in plastics vs 93% for PFAS.

The researchers then estimated that the total plastic-attributable disease burden in the United States in 2018 cost the nation $249 billion, or 1.22% of the gross domestic product. Of this, $159 billion was linked to PDBE exposure, which is associated with diseases such as cancer.

Moreover, $1.02 billion plastic-attributable disease burden was associated with bisphenol A exposure, which can have potentially harmful health effects on the immune system; followed by $66.7 billion due to phthalates, which are linked to preterm birth, reduced sperm count, and childhood obesity; and $22.4 billion due to PFAS, which are associated with kidney failure and gestational diabetes.

The study was supported by the National Institutes of Health and the Passport Foundation.

Dr. Trasande declared relationships with Audible, Houghton Mifflin, Paidos, and Kobunsha, none of which relate to the present manuscript.

No other financial relationships were declared.

A version of this article appeared on Medscape.com.

Exposure to endocrine-disrupting chemicals (EDCs) via daily use of plastics is a major contributor to the overall disease burden in the United States and the associated costs to society amount to more than 1% of the gross domestic product, revealed a large-scale analysis.

The research, published in the Journal of the Endocrine Society, indicated that taken together, the disease burden attributable to EDCs used in the manufacture of plastics added up to almost $250 billion in 2018 alone.

“The diseases due to plastics run the entire life course from preterm birth to obesity, heart disease, and cancers,” commented lead author Leonardo Trasande, MD, MPP, Jim G. Hendrick, MD Professor of Pediatrics, Department of Pediatrics, NYU Langone Medical Center, New York, in a release.

“Our study drives home the need to address chemicals used in plastic materials” through global treaties and other policy initiatives, he said, so as to “reduce these costs” in line with reductions in exposure to the chemicals.

Co-author Michael Belliveau, Executive Director at Defend Our Health in Portland, ME, agreed, saying: “We can reduce these health costs and the prevalence of chronic endocrine diseases such as diabetes and obesity if governments and companies enact policies that minimize exposure to EDCs to protect public health and the environment.”

Plastics may contain any one of a number of EDCs, such as polybrominated diphenylethers in flame retardant additives, phthalates in food packaging, bisphenols in can linings, and perfluoroalkyl and polyfluoroalkyl substances (PFAS) in nonstick cooking utensils.

These chemicals have been shown to leach and disturb the body’s hormone systems, increasing the risk for cancer, diabetes, reproductive disorders, neurological impairments in developing fetuses and children, and even death.

In March 2022, the United Nations Environment Assembly committed to a global plastics treaty to “end plastic pollution and forge an international legally binding agreement by 2024” that “addresses the full life cycle of plastic, including its production, design and disposal.”

Minimizing EDC Exposure

But what can doctors tell their patients today to help them reduce their exposure to EDCs?

“There are safe and simple steps that people can take to limit their exposure to the chemicals of greatest concern,” Dr. Trasande told this news organization.

This can be partly achieved by reducing plastic use down to its essentials. “To use an example, when you are flying, fill up a stainless steel container after clearing security. At home, use glass or stainless steel” rather than plastic bottles or containers.

In particular, “avoiding microwaving plastic is important,” Dr. Trasande said, “even if a container says it’s microwave-safe.”

He warned that “many chemicals used in plastic are not covalently bound, and heat facilitates leaching into food. Microscopic contaminants can also get into food when you microwave plastic.”

Dr. Trasande also suggests limiting canned food consumption and avoiding cleaning plastic food containers in machine dishwashers.

Calculating the Disease Burden

To accurately assess the “the tradeoffs involved in the ongoing reliance on plastic production as a source of economic productivity,” the current researchers calculated the attributable disease burden and cost related to EDCs used in plastic materials in the United States in 2018.

Building on previously published analyses, they used industry reports, publications by national and international governing bodies, and peer-reviewed publications to determine the usage of each type of EDC and its attributable disease and disability burden.

This plastic-related fraction (PRF) of disease burden was then used to calculate an updated cost estimate for each EDC, based on the assumption that the disease burden is directly proportional to its exposure.

They found that for bisphenol A, 97.5% of its use, and therefore its estimated PRF of disease burden, was related to the manufacture of plastics, while this figure was 98%-100% for phthalates. For PDBE, 98% of its use was in plastics vs 93% for PFAS.

The researchers then estimated that the total plastic-attributable disease burden in the United States in 2018 cost the nation $249 billion, or 1.22% of the gross domestic product. Of this, $159 billion was linked to PDBE exposure, which is associated with diseases such as cancer.

Moreover, $1.02 billion plastic-attributable disease burden was associated with bisphenol A exposure, which can have potentially harmful health effects on the immune system; followed by $66.7 billion due to phthalates, which are linked to preterm birth, reduced sperm count, and childhood obesity; and $22.4 billion due to PFAS, which are associated with kidney failure and gestational diabetes.

The study was supported by the National Institutes of Health and the Passport Foundation.

Dr. Trasande declared relationships with Audible, Houghton Mifflin, Paidos, and Kobunsha, none of which relate to the present manuscript.

No other financial relationships were declared.

A version of this article appeared on Medscape.com.

Exposure to endocrine-disrupting chemicals (EDCs) via daily use of plastics is a major contributor to the overall disease burden in the United States and the associated costs to society amount to more than 1% of the gross domestic product, revealed a large-scale analysis.

The research, published in the Journal of the Endocrine Society, indicated that taken together, the disease burden attributable to EDCs used in the manufacture of plastics added up to almost $250 billion in 2018 alone.

“The diseases due to plastics run the entire life course from preterm birth to obesity, heart disease, and cancers,” commented lead author Leonardo Trasande, MD, MPP, Jim G. Hendrick, MD Professor of Pediatrics, Department of Pediatrics, NYU Langone Medical Center, New York, in a release.

“Our study drives home the need to address chemicals used in plastic materials” through global treaties and other policy initiatives, he said, so as to “reduce these costs” in line with reductions in exposure to the chemicals.

Co-author Michael Belliveau, Executive Director at Defend Our Health in Portland, ME, agreed, saying: “We can reduce these health costs and the prevalence of chronic endocrine diseases such as diabetes and obesity if governments and companies enact policies that minimize exposure to EDCs to protect public health and the environment.”

Plastics may contain any one of a number of EDCs, such as polybrominated diphenylethers in flame retardant additives, phthalates in food packaging, bisphenols in can linings, and perfluoroalkyl and polyfluoroalkyl substances (PFAS) in nonstick cooking utensils.

These chemicals have been shown to leach and disturb the body’s hormone systems, increasing the risk for cancer, diabetes, reproductive disorders, neurological impairments in developing fetuses and children, and even death.

In March 2022, the United Nations Environment Assembly committed to a global plastics treaty to “end plastic pollution and forge an international legally binding agreement by 2024” that “addresses the full life cycle of plastic, including its production, design and disposal.”

Minimizing EDC Exposure

But what can doctors tell their patients today to help them reduce their exposure to EDCs?

“There are safe and simple steps that people can take to limit their exposure to the chemicals of greatest concern,” Dr. Trasande told this news organization.

This can be partly achieved by reducing plastic use down to its essentials. “To use an example, when you are flying, fill up a stainless steel container after clearing security. At home, use glass or stainless steel” rather than plastic bottles or containers.

In particular, “avoiding microwaving plastic is important,” Dr. Trasande said, “even if a container says it’s microwave-safe.”

He warned that “many chemicals used in plastic are not covalently bound, and heat facilitates leaching into food. Microscopic contaminants can also get into food when you microwave plastic.”

Dr. Trasande also suggests limiting canned food consumption and avoiding cleaning plastic food containers in machine dishwashers.

Calculating the Disease Burden

To accurately assess the “the tradeoffs involved in the ongoing reliance on plastic production as a source of economic productivity,” the current researchers calculated the attributable disease burden and cost related to EDCs used in plastic materials in the United States in 2018.

Building on previously published analyses, they used industry reports, publications by national and international governing bodies, and peer-reviewed publications to determine the usage of each type of EDC and its attributable disease and disability burden.

This plastic-related fraction (PRF) of disease burden was then used to calculate an updated cost estimate for each EDC, based on the assumption that the disease burden is directly proportional to its exposure.

They found that for bisphenol A, 97.5% of its use, and therefore its estimated PRF of disease burden, was related to the manufacture of plastics, while this figure was 98%-100% for phthalates. For PDBE, 98% of its use was in plastics vs 93% for PFAS.

The researchers then estimated that the total plastic-attributable disease burden in the United States in 2018 cost the nation $249 billion, or 1.22% of the gross domestic product. Of this, $159 billion was linked to PDBE exposure, which is associated with diseases such as cancer.

Moreover, $1.02 billion plastic-attributable disease burden was associated with bisphenol A exposure, which can have potentially harmful health effects on the immune system; followed by $66.7 billion due to phthalates, which are linked to preterm birth, reduced sperm count, and childhood obesity; and $22.4 billion due to PFAS, which are associated with kidney failure and gestational diabetes.

The study was supported by the National Institutes of Health and the Passport Foundation.

Dr. Trasande declared relationships with Audible, Houghton Mifflin, Paidos, and Kobunsha, none of which relate to the present manuscript.

No other financial relationships were declared.

A version of this article appeared on Medscape.com.

FAIRFAX, VIRGINIA — The lack of data on optimal timing of delivery for pregnancies complicated by diabetes remains a major challenge in obstetrics — one with considerable implications given the high and rising prevalence of pregestational and gestational diabetes, Katherine Laughon Grantz, MD, MS, of the National Institute of Child Health and Human Development, said at the biennial meeting of the Diabetes in Pregnancy Study Group of North America.

“While 39-40 weeks might be ideal for low-risk pregnancies, the optimal timing for pregnancies with complications [like diabetes] is unknown,” said Dr. Grantz, a senior investigator in the NICHD’s epidemiology branch.

The percentage of mothers with gestational diabetes mellitus (GDM) increased from 6% in 2016 to 8% in 2021, according to the most recent data from the National Vital Statistics System of the Centers for Disease Control and Prevention (MMWR Morb Mortal Wkly Rep. 2023;72:16). Meanwhile, the prevalence of prepregnancy obesity, which raises the risk of gestational and type 2 diabetes, was 29% in 2019; this represents an 11% increase from 2015 (NCHS Data Brief. 2020;392:1-8) and has occurred across all maternal ages, races, ethnic groups, and educational levels, she said.

“The reason clinicians deliver pregnancies with diabetes earlier is because there’s a decreased risk of macrosomia, shoulder dystocia, and stillbirth. And these risks need to be balanced with the increased risk of neonatal morbidity and mortality associated with earlier delivery,” said Dr. Grantz, who noted during her talk that delivery timing also appears to influence long-term neurodevelopmental outcomes. “Yet despite [diabetes in pregnancy] being so common, there is complete uncertainty about when to deliver.”
 

ACOG Recommendations, Randomized Trials (New And Old)

The American College of Obstetricians and Gynecologists, in a Committee Opinion on Medically Indicated Late-Preterm and Early-Term Deliveries, published in collaboration with the Society of Maternal-Fetal Medicine, offers recommendations based on the type of diabetes and the level of control. For instance, the suggested delivery timing for well-controlled GDM is full term (39 0/7 to 40 6/7 weeks of gestation), while the recommendation for poorly controlled diabetes is individualized late preterm/early term management (Obstet Gynecol. 2021;138:e35-9).

In defining and evaluating control, she noted, “the clinical focus is on glucose, but there are likely other important parameters that are not taken into account ... which [could be] important when considering the timing of delivery.” Potentially important factors include estimated fetal weight, fetal growth velocity, lipids, and amino acids, she said.

ACOG’s recommendations are based mainly on retrospective data, Dr. Grantz said. Only two randomized controlled trials have investigated the timing of delivery in the context of diabetes, and both focused on cesarean section and were “generally underpowered to study neonatal outcomes,” she said.

The first RCT, published in 1993, enrolled 200 women with uncomplicated insulin-requiring diabetes (187 with GDM and 13 with pregestational diabetes) at 38 weeks of gestation, and compared active induction of labor within 5 days to expectant management. There was no significant difference in the cesarean delivery rate (the primary outcome), but rates of macrosomia and large for gestational age were higher in the expectant management group (27% vs. 15%, P = .05, and 23% vs. 10%, P = .02, respectively). Shoulder dystocia occurred in three deliveries, each of which was expectantly managed (Am J Obstet Gynecol. 1993;169[3]:611-5). Notably, the study included “only women with excellent glucose control,” Dr. Grantz said.

The second RCT, published in 2017 by a group in Italy, enrolled 425 patients with GDM (diagnosed by the International Association of Diabetes and Pregnancy Study Groups criteria) between week 38 and week 39 of gestation and similarly randomized them to induction of labor or expectant management. No difference in cesarean delivery was found (BJOG. 2017;124[4]:669-77). Induction of labor was associated with a higher risk of hyperbilirubinemia, and there was a trend toward a decreased risk of macrosomia, but again, the study was underpowered to detect differences in most outcomes, she said. (The study also was stopped early because of an inability to recruit, she noted.)

Dr. Grantz is currently recruiting for a randomized trial aimed at determining the optimal time between 37 and 39 weeks to initiate delivery — the time when neonatal morbidity and perinatal mortality risk is the lowest – for uncontrolled GDM-complicated pregnancies. The trial is designed to recruit up to 3,450 pregnant women with uncontrolled GDM and randomize the timing of their delivery (NCT05515744).

Those who are eligible for the study but do not consent to participate in randomization for delivery will be asked about chart review only (an estimated additional 3,000). The SPAN TIME study will also assess newborn development and behavior outcomes, as well as anthropometric measures, as secondary outcomes. An exploratory analysis will look for clinical, nonclinical or biochemical factors that could be helpful in optimizing delivery timing.

What Retrospective Studies Reveal

Factors that may influence the timing of delivery include the duration of neonatal exposure to hyperglycemia/hyperinsulinemia (pregestational vs. gestational diabetes), the level of diabetes control, and comorbidities (e.g. maternal renal disease or chronic hypertension). However, research “investigating how these factors influence morbidity and the timing of delivery is limited,” said Dr. Grantz.

Overall, it has been difficult through retrospective studies, she said, to investigate neonatal morbidity in diabetic pregnancies and tease apart the relative effects of diabetes as a precursor for early delivery and prematurity itself. Among the studies suggesting an independent risk of diabetes is a retrospective study focusing on neonatal respiratory morbidity — “one of the most common adverse outcomes associated with diabetes.”

The study, an analysis of the Consortium on Safe Labor study (an electronic medical record study of more than 220,000 singleton pregnancies), stratified morbidity by the probability of delivering at term (≥ 37 weeks). GDM and pregestational diabetes complicated 5.1% and 1.5% of the pregnancies, respectively, and were found to be associated with increased risks of neonatal respiratory morbidity compared to women without diabetes — regardless of the probability of delivering at term.

However, these associations were stronger with a higher probability of delivering at term, which suggests that the neonatal respiratory morbidity associated with diabetes is not fully explained by a greater propensity for prematurity (Am J Perinatol. 2017;34[11]:1160-8).

In addition, the rates of all neonatal respiratory morbidities and mortality were higher for pregestational diabetes compared with gestational diabetes, said Dr. Grantz, a senior author of the study. (Morbidities included neonatal intensive care unit admission, transient tachypnea of newborn, apnea, respiratory distress syndrome, mechanical ventilation, and stillbirth.)

The pathophysiology of diabetes and neonatal respiratory morbidity is “not fully known,” she said. It is believed that fetal hyperinsulinemia may cause delayed pulmonary maturation and there is evidence from animal studies that insulin decreases the incorporation of glucose and fatty acids into phospholipid phosphatidylglycerol. Indirect effects stem from the physiologic immaturity of earlier delivery and a higher cesarean delivery rate in pregnancies complicated by diabetes, Dr. Grantz said.

Among other retrospective studies was a population-based study from Canada (2004-2014), published in 2020, of large numbers of women with all types of diabetes and a comparison group of over 2.5 million without diabetes. For maternal morbidity/mortality, there were no significant differences by gestational age between iatrogenic delivery and expectant management among any form of diabetes. But for neonatal morbidity and mortality, the study found differences.

In women with gestational diabetes, iatrogenic delivery was associated with increased risk of neonatal morbidity/mortality at 36 and 37 weeks’ gestation and with decreased risk at weeks 38-40. Increased risk with iatrogenic delivery was also found for women with type 1 and type 2 diabetes at weeks 36 and 37 (Acta Obstet Gynecol Scand. 2020;99[3]:341-9).

Another retrospective study using California vital statistics (1997-2006) examined rates of stillbirth and infant death in women with GDM by gestational age at delivery (Am J Obstet Gynecol. 2012;206[4]:309.e1-e7). The 190,000-plus women with GDM had elevated risk of stillbirth at each gestational age compared to those without GDM, but “the [excess] risk for GDM was lowest at 38 weeks and again at 40 weeks,” Dr. Grantz said. The investigators concluded, she said, “that the risk of expectant management exceeded that of delivery at 38 weeks and beyond.”

Dr. Grantz reported no disclosures.

FAIRFAX, VIRGINIA — The lack of data on optimal timing of delivery for pregnancies complicated by diabetes remains a major challenge in obstetrics — one with considerable implications given the high and rising prevalence of pregestational and gestational diabetes, Katherine Laughon Grantz, MD, MS, of the National Institute of Child Health and Human Development, said at the biennial meeting of the Diabetes in Pregnancy Study Group of North America.

“While 39-40 weeks might be ideal for low-risk pregnancies, the optimal timing for pregnancies with complications [like diabetes] is unknown,” said Dr. Grantz, a senior investigator in the NICHD’s epidemiology branch.

The percentage of mothers with gestational diabetes mellitus (GDM) increased from 6% in 2016 to 8% in 2021, according to the most recent data from the National Vital Statistics System of the Centers for Disease Control and Prevention (MMWR Morb Mortal Wkly Rep. 2023;72:16). Meanwhile, the prevalence of prepregnancy obesity, which raises the risk of gestational and type 2 diabetes, was 29% in 2019; this represents an 11% increase from 2015 (NCHS Data Brief. 2020;392:1-8) and has occurred across all maternal ages, races, ethnic groups, and educational levels, she said.

“The reason clinicians deliver pregnancies with diabetes earlier is because there’s a decreased risk of macrosomia, shoulder dystocia, and stillbirth. And these risks need to be balanced with the increased risk of neonatal morbidity and mortality associated with earlier delivery,” said Dr. Grantz, who noted during her talk that delivery timing also appears to influence long-term neurodevelopmental outcomes. “Yet despite [diabetes in pregnancy] being so common, there is complete uncertainty about when to deliver.”
 

ACOG Recommendations, Randomized Trials (New And Old)

The American College of Obstetricians and Gynecologists, in a Committee Opinion on Medically Indicated Late-Preterm and Early-Term Deliveries, published in collaboration with the Society of Maternal-Fetal Medicine, offers recommendations based on the type of diabetes and the level of control. For instance, the suggested delivery timing for well-controlled GDM is full term (39 0/7 to 40 6/7 weeks of gestation), while the recommendation for poorly controlled diabetes is individualized late preterm/early term management (Obstet Gynecol. 2021;138:e35-9).

In defining and evaluating control, she noted, “the clinical focus is on glucose, but there are likely other important parameters that are not taken into account ... which [could be] important when considering the timing of delivery.” Potentially important factors include estimated fetal weight, fetal growth velocity, lipids, and amino acids, she said.

ACOG’s recommendations are based mainly on retrospective data, Dr. Grantz said. Only two randomized controlled trials have investigated the timing of delivery in the context of diabetes, and both focused on cesarean section and were “generally underpowered to study neonatal outcomes,” she said.

The first RCT, published in 1993, enrolled 200 women with uncomplicated insulin-requiring diabetes (187 with GDM and 13 with pregestational diabetes) at 38 weeks of gestation, and compared active induction of labor within 5 days to expectant management. There was no significant difference in the cesarean delivery rate (the primary outcome), but rates of macrosomia and large for gestational age were higher in the expectant management group (27% vs. 15%, P = .05, and 23% vs. 10%, P = .02, respectively). Shoulder dystocia occurred in three deliveries, each of which was expectantly managed (Am J Obstet Gynecol. 1993;169[3]:611-5). Notably, the study included “only women with excellent glucose control,” Dr. Grantz said.

The second RCT, published in 2017 by a group in Italy, enrolled 425 patients with GDM (diagnosed by the International Association of Diabetes and Pregnancy Study Groups criteria) between week 38 and week 39 of gestation and similarly randomized them to induction of labor or expectant management. No difference in cesarean delivery was found (BJOG. 2017;124[4]:669-77). Induction of labor was associated with a higher risk of hyperbilirubinemia, and there was a trend toward a decreased risk of macrosomia, but again, the study was underpowered to detect differences in most outcomes, she said. (The study also was stopped early because of an inability to recruit, she noted.)

Dr. Grantz is currently recruiting for a randomized trial aimed at determining the optimal time between 37 and 39 weeks to initiate delivery — the time when neonatal morbidity and perinatal mortality risk is the lowest – for uncontrolled GDM-complicated pregnancies. The trial is designed to recruit up to 3,450 pregnant women with uncontrolled GDM and randomize the timing of their delivery (NCT05515744).

Those who are eligible for the study but do not consent to participate in randomization for delivery will be asked about chart review only (an estimated additional 3,000). The SPAN TIME study will also assess newborn development and behavior outcomes, as well as anthropometric measures, as secondary outcomes. An exploratory analysis will look for clinical, nonclinical or biochemical factors that could be helpful in optimizing delivery timing.

What Retrospective Studies Reveal

Factors that may influence the timing of delivery include the duration of neonatal exposure to hyperglycemia/hyperinsulinemia (pregestational vs. gestational diabetes), the level of diabetes control, and comorbidities (e.g. maternal renal disease or chronic hypertension). However, research “investigating how these factors influence morbidity and the timing of delivery is limited,” said Dr. Grantz.

Overall, it has been difficult through retrospective studies, she said, to investigate neonatal morbidity in diabetic pregnancies and tease apart the relative effects of diabetes as a precursor for early delivery and prematurity itself. Among the studies suggesting an independent risk of diabetes is a retrospective study focusing on neonatal respiratory morbidity — “one of the most common adverse outcomes associated with diabetes.”

The study, an analysis of the Consortium on Safe Labor study (an electronic medical record study of more than 220,000 singleton pregnancies), stratified morbidity by the probability of delivering at term (≥ 37 weeks). GDM and pregestational diabetes complicated 5.1% and 1.5% of the pregnancies, respectively, and were found to be associated with increased risks of neonatal respiratory morbidity compared to women without diabetes — regardless of the probability of delivering at term.

However, these associations were stronger with a higher probability of delivering at term, which suggests that the neonatal respiratory morbidity associated with diabetes is not fully explained by a greater propensity for prematurity (Am J Perinatol. 2017;34[11]:1160-8).

In addition, the rates of all neonatal respiratory morbidities and mortality were higher for pregestational diabetes compared with gestational diabetes, said Dr. Grantz, a senior author of the study. (Morbidities included neonatal intensive care unit admission, transient tachypnea of newborn, apnea, respiratory distress syndrome, mechanical ventilation, and stillbirth.)

The pathophysiology of diabetes and neonatal respiratory morbidity is “not fully known,” she said. It is believed that fetal hyperinsulinemia may cause delayed pulmonary maturation and there is evidence from animal studies that insulin decreases the incorporation of glucose and fatty acids into phospholipid phosphatidylglycerol. Indirect effects stem from the physiologic immaturity of earlier delivery and a higher cesarean delivery rate in pregnancies complicated by diabetes, Dr. Grantz said.

Among other retrospective studies was a population-based study from Canada (2004-2014), published in 2020, of large numbers of women with all types of diabetes and a comparison group of over 2.5 million without diabetes. For maternal morbidity/mortality, there were no significant differences by gestational age between iatrogenic delivery and expectant management among any form of diabetes. But for neonatal morbidity and mortality, the study found differences.

In women with gestational diabetes, iatrogenic delivery was associated with increased risk of neonatal morbidity/mortality at 36 and 37 weeks’ gestation and with decreased risk at weeks 38-40. Increased risk with iatrogenic delivery was also found for women with type 1 and type 2 diabetes at weeks 36 and 37 (Acta Obstet Gynecol Scand. 2020;99[3]:341-9).

Another retrospective study using California vital statistics (1997-2006) examined rates of stillbirth and infant death in women with GDM by gestational age at delivery (Am J Obstet Gynecol. 2012;206[4]:309.e1-e7). The 190,000-plus women with GDM had elevated risk of stillbirth at each gestational age compared to those without GDM, but “the [excess] risk for GDM was lowest at 38 weeks and again at 40 weeks,” Dr. Grantz said. The investigators concluded, she said, “that the risk of expectant management exceeded that of delivery at 38 weeks and beyond.”

Dr. Grantz reported no disclosures.

FAIRFAX, VIRGINIA — The lack of data on optimal timing of delivery for pregnancies complicated by diabetes remains a major challenge in obstetrics — one with considerable implications given the high and rising prevalence of pregestational and gestational diabetes, Katherine Laughon Grantz, MD, MS, of the National Institute of Child Health and Human Development, said at the biennial meeting of the Diabetes in Pregnancy Study Group of North America.

“While 39-40 weeks might be ideal for low-risk pregnancies, the optimal timing for pregnancies with complications [like diabetes] is unknown,” said Dr. Grantz, a senior investigator in the NICHD’s epidemiology branch.

The percentage of mothers with gestational diabetes mellitus (GDM) increased from 6% in 2016 to 8% in 2021, according to the most recent data from the National Vital Statistics System of the Centers for Disease Control and Prevention (MMWR Morb Mortal Wkly Rep. 2023;72:16). Meanwhile, the prevalence of prepregnancy obesity, which raises the risk of gestational and type 2 diabetes, was 29% in 2019; this represents an 11% increase from 2015 (NCHS Data Brief. 2020;392:1-8) and has occurred across all maternal ages, races, ethnic groups, and educational levels, she said.

“The reason clinicians deliver pregnancies with diabetes earlier is because there’s a decreased risk of macrosomia, shoulder dystocia, and stillbirth. And these risks need to be balanced with the increased risk of neonatal morbidity and mortality associated with earlier delivery,” said Dr. Grantz, who noted during her talk that delivery timing also appears to influence long-term neurodevelopmental outcomes. “Yet despite [diabetes in pregnancy] being so common, there is complete uncertainty about when to deliver.”
 

ACOG Recommendations, Randomized Trials (New And Old)

The American College of Obstetricians and Gynecologists, in a Committee Opinion on Medically Indicated Late-Preterm and Early-Term Deliveries, published in collaboration with the Society of Maternal-Fetal Medicine, offers recommendations based on the type of diabetes and the level of control. For instance, the suggested delivery timing for well-controlled GDM is full term (39 0/7 to 40 6/7 weeks of gestation), while the recommendation for poorly controlled diabetes is individualized late preterm/early term management (Obstet Gynecol. 2021;138:e35-9).

In defining and evaluating control, she noted, “the clinical focus is on glucose, but there are likely other important parameters that are not taken into account ... which [could be] important when considering the timing of delivery.” Potentially important factors include estimated fetal weight, fetal growth velocity, lipids, and amino acids, she said.

ACOG’s recommendations are based mainly on retrospective data, Dr. Grantz said. Only two randomized controlled trials have investigated the timing of delivery in the context of diabetes, and both focused on cesarean section and were “generally underpowered to study neonatal outcomes,” she said.

The first RCT, published in 1993, enrolled 200 women with uncomplicated insulin-requiring diabetes (187 with GDM and 13 with pregestational diabetes) at 38 weeks of gestation, and compared active induction of labor within 5 days to expectant management. There was no significant difference in the cesarean delivery rate (the primary outcome), but rates of macrosomia and large for gestational age were higher in the expectant management group (27% vs. 15%, P = .05, and 23% vs. 10%, P = .02, respectively). Shoulder dystocia occurred in three deliveries, each of which was expectantly managed (Am J Obstet Gynecol. 1993;169[3]:611-5). Notably, the study included “only women with excellent glucose control,” Dr. Grantz said.

The second RCT, published in 2017 by a group in Italy, enrolled 425 patients with GDM (diagnosed by the International Association of Diabetes and Pregnancy Study Groups criteria) between week 38 and week 39 of gestation and similarly randomized them to induction of labor or expectant management. No difference in cesarean delivery was found (BJOG. 2017;124[4]:669-77). Induction of labor was associated with a higher risk of hyperbilirubinemia, and there was a trend toward a decreased risk of macrosomia, but again, the study was underpowered to detect differences in most outcomes, she said. (The study also was stopped early because of an inability to recruit, she noted.)

Dr. Grantz is currently recruiting for a randomized trial aimed at determining the optimal time between 37 and 39 weeks to initiate delivery — the time when neonatal morbidity and perinatal mortality risk is the lowest – for uncontrolled GDM-complicated pregnancies. The trial is designed to recruit up to 3,450 pregnant women with uncontrolled GDM and randomize the timing of their delivery (NCT05515744).

Those who are eligible for the study but do not consent to participate in randomization for delivery will be asked about chart review only (an estimated additional 3,000). The SPAN TIME study will also assess newborn development and behavior outcomes, as well as anthropometric measures, as secondary outcomes. An exploratory analysis will look for clinical, nonclinical or biochemical factors that could be helpful in optimizing delivery timing.

What Retrospective Studies Reveal

Factors that may influence the timing of delivery include the duration of neonatal exposure to hyperglycemia/hyperinsulinemia (pregestational vs. gestational diabetes), the level of diabetes control, and comorbidities (e.g. maternal renal disease or chronic hypertension). However, research “investigating how these factors influence morbidity and the timing of delivery is limited,” said Dr. Grantz.

Overall, it has been difficult through retrospective studies, she said, to investigate neonatal morbidity in diabetic pregnancies and tease apart the relative effects of diabetes as a precursor for early delivery and prematurity itself. Among the studies suggesting an independent risk of diabetes is a retrospective study focusing on neonatal respiratory morbidity — “one of the most common adverse outcomes associated with diabetes.”

The study, an analysis of the Consortium on Safe Labor study (an electronic medical record study of more than 220,000 singleton pregnancies), stratified morbidity by the probability of delivering at term (≥ 37 weeks). GDM and pregestational diabetes complicated 5.1% and 1.5% of the pregnancies, respectively, and were found to be associated with increased risks of neonatal respiratory morbidity compared to women without diabetes — regardless of the probability of delivering at term.

However, these associations were stronger with a higher probability of delivering at term, which suggests that the neonatal respiratory morbidity associated with diabetes is not fully explained by a greater propensity for prematurity (Am J Perinatol. 2017;34[11]:1160-8).

In addition, the rates of all neonatal respiratory morbidities and mortality were higher for pregestational diabetes compared with gestational diabetes, said Dr. Grantz, a senior author of the study. (Morbidities included neonatal intensive care unit admission, transient tachypnea of newborn, apnea, respiratory distress syndrome, mechanical ventilation, and stillbirth.)

The pathophysiology of diabetes and neonatal respiratory morbidity is “not fully known,” she said. It is believed that fetal hyperinsulinemia may cause delayed pulmonary maturation and there is evidence from animal studies that insulin decreases the incorporation of glucose and fatty acids into phospholipid phosphatidylglycerol. Indirect effects stem from the physiologic immaturity of earlier delivery and a higher cesarean delivery rate in pregnancies complicated by diabetes, Dr. Grantz said.

Among other retrospective studies was a population-based study from Canada (2004-2014), published in 2020, of large numbers of women with all types of diabetes and a comparison group of over 2.5 million without diabetes. For maternal morbidity/mortality, there were no significant differences by gestational age between iatrogenic delivery and expectant management among any form of diabetes. But for neonatal morbidity and mortality, the study found differences.

In women with gestational diabetes, iatrogenic delivery was associated with increased risk of neonatal morbidity/mortality at 36 and 37 weeks’ gestation and with decreased risk at weeks 38-40. Increased risk with iatrogenic delivery was also found for women with type 1 and type 2 diabetes at weeks 36 and 37 (Acta Obstet Gynecol Scand. 2020;99[3]:341-9).

Another retrospective study using California vital statistics (1997-2006) examined rates of stillbirth and infant death in women with GDM by gestational age at delivery (Am J Obstet Gynecol. 2012;206[4]:309.e1-e7). The 190,000-plus women with GDM had elevated risk of stillbirth at each gestational age compared to those without GDM, but “the [excess] risk for GDM was lowest at 38 weeks and again at 40 weeks,” Dr. Grantz said. The investigators concluded, she said, “that the risk of expectant management exceeded that of delivery at 38 weeks and beyond.”

Dr. Grantz reported no disclosures.

TOPLINE:

Dermatomyositis (DM) is associated with an increased risk for cardiovascular comorbidities, including chronic kidney disease, a new study found.

METHODOLOGY:

• DM is associated with cardiovascular disease (CVD), but US-based data studies on CVD comorbidities in patients with DM are lacking.
• In a cross-sectional analysis of participants in the All of Us research program aged 18 years and older with at least 1 year of electronic health record (EHR) data, researchers identified DM cases and controls with nearest neighbor propensity score matching by age, sex, race/ethnicity, EHR duration, and healthcare visit quantity.
• They used the Pearson’s chi-squared test, Fisher’s exact test, unpaired t-test, or Mann-Whitney U test to compare clinical characteristics and traditional CV comorbidities.
• Multivariable conditional logistic regression was used with backward elimination of comorbidities with P > .1 or evidence of collinearity.

TAKEAWAY:

• Among 235,161 All of Us participants, researchers identified 206 DM cases and 824 matched controls with largely similar demographic characteristics, including smoking status, obesity, and indicators of socioeconomic status.
• Participants with DM were more likely to have a history of atrial fibrillation (10.1% vs 16.0%, respectively), chronic kidney disease (15.2% vs 29.1%), congestive heart failure (9.6% vs 18.0%), coronary artery disease (CAD) (18.2% vs 34.0%), hypertension (52.5% vs 60.7%), myocardial infarction (7.4% vs 15.0), type 2 diabetes (27.3% vs 47.6%), and valvular heart disease (8.7% vs 16.5%) than matched controls.
• In a multivariable analysis that adjusted for potential confounders, three comorbidities remained associated with DM: CAD (odds ratio [OR], 2.0; P < .001), type 2 diabetes (OR, 2.2; P < .001), and chronic kidney disease (OR, 1.7; P = .015).

IN PRACTICE:

“Our findings are important both for prognosis and clinical care, suggesting DM patients should be screened for CVD risk factors to potentially reduce the increased risk for cardiovascular events and CVD-related mortality in DM,” the authors concluded.

SOURCE:

Corresponding author Alisa N. Femia, MD, of the department of dermatology at NYU Grossman School of Medicine, led the research. The study was published online in the Journal of the American Academy of Dermatology.

LIMITATIONS:

How DM treatments might influence CVD development was not addressed. EHRs may have diagnostic inaccuracies and omissions and lack data on clinical features and severity.

DISCLOSURES:

The project was supported by the National Center for Advancing Translational Sciences, National Institutes of Health. Dr. Femia reported consulting fees from Octagon Therapeutics, Timber Pharmaceuticals, and Guidepoint. Study author Michael S. Garshick, MD, reported consulting fees from AbbVie and Horizon Therapeutics. The remaining authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Dermatomyositis (DM) is associated with an increased risk for cardiovascular comorbidities, including chronic kidney disease, a new study found.

METHODOLOGY:

• DM is associated with cardiovascular disease (CVD), but US-based data studies on CVD comorbidities in patients with DM are lacking.
• In a cross-sectional analysis of participants in the All of Us research program aged 18 years and older with at least 1 year of electronic health record (EHR) data, researchers identified DM cases and controls with nearest neighbor propensity score matching by age, sex, race/ethnicity, EHR duration, and healthcare visit quantity.
• They used the Pearson’s chi-squared test, Fisher’s exact test, unpaired t-test, or Mann-Whitney U test to compare clinical characteristics and traditional CV comorbidities.
• Multivariable conditional logistic regression was used with backward elimination of comorbidities with P > .1 or evidence of collinearity.

TAKEAWAY:

• Among 235,161 All of Us participants, researchers identified 206 DM cases and 824 matched controls with largely similar demographic characteristics, including smoking status, obesity, and indicators of socioeconomic status.
• Participants with DM were more likely to have a history of atrial fibrillation (10.1% vs 16.0%, respectively), chronic kidney disease (15.2% vs 29.1%), congestive heart failure (9.6% vs 18.0%), coronary artery disease (CAD) (18.2% vs 34.0%), hypertension (52.5% vs 60.7%), myocardial infarction (7.4% vs 15.0), type 2 diabetes (27.3% vs 47.6%), and valvular heart disease (8.7% vs 16.5%) than matched controls.
• In a multivariable analysis that adjusted for potential confounders, three comorbidities remained associated with DM: CAD (odds ratio [OR], 2.0; P < .001), type 2 diabetes (OR, 2.2; P < .001), and chronic kidney disease (OR, 1.7; P = .015).

IN PRACTICE:

“Our findings are important both for prognosis and clinical care, suggesting DM patients should be screened for CVD risk factors to potentially reduce the increased risk for cardiovascular events and CVD-related mortality in DM,” the authors concluded.

SOURCE:

Corresponding author Alisa N. Femia, MD, of the department of dermatology at NYU Grossman School of Medicine, led the research. The study was published online in the Journal of the American Academy of Dermatology.

LIMITATIONS:

How DM treatments might influence CVD development was not addressed. EHRs may have diagnostic inaccuracies and omissions and lack data on clinical features and severity.

DISCLOSURES:

The project was supported by the National Center for Advancing Translational Sciences, National Institutes of Health. Dr. Femia reported consulting fees from Octagon Therapeutics, Timber Pharmaceuticals, and Guidepoint. Study author Michael S. Garshick, MD, reported consulting fees from AbbVie and Horizon Therapeutics. The remaining authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Dermatomyositis (DM) is associated with an increased risk for cardiovascular comorbidities, including chronic kidney disease, a new study found.

METHODOLOGY:

• DM is associated with cardiovascular disease (CVD), but US-based data studies on CVD comorbidities in patients with DM are lacking.
• In a cross-sectional analysis of participants in the All of Us research program aged 18 years and older with at least 1 year of electronic health record (EHR) data, researchers identified DM cases and controls with nearest neighbor propensity score matching by age, sex, race/ethnicity, EHR duration, and healthcare visit quantity.
• They used the Pearson’s chi-squared test, Fisher’s exact test, unpaired t-test, or Mann-Whitney U test to compare clinical characteristics and traditional CV comorbidities.
• Multivariable conditional logistic regression was used with backward elimination of comorbidities with P > .1 or evidence of collinearity.

TAKEAWAY:

• Among 235,161 All of Us participants, researchers identified 206 DM cases and 824 matched controls with largely similar demographic characteristics, including smoking status, obesity, and indicators of socioeconomic status.
• Participants with DM were more likely to have a history of atrial fibrillation (10.1% vs 16.0%, respectively), chronic kidney disease (15.2% vs 29.1%), congestive heart failure (9.6% vs 18.0%), coronary artery disease (CAD) (18.2% vs 34.0%), hypertension (52.5% vs 60.7%), myocardial infarction (7.4% vs 15.0), type 2 diabetes (27.3% vs 47.6%), and valvular heart disease (8.7% vs 16.5%) than matched controls.
• In a multivariable analysis that adjusted for potential confounders, three comorbidities remained associated with DM: CAD (odds ratio [OR], 2.0; P < .001), type 2 diabetes (OR, 2.2; P < .001), and chronic kidney disease (OR, 1.7; P = .015).

IN PRACTICE:

“Our findings are important both for prognosis and clinical care, suggesting DM patients should be screened for CVD risk factors to potentially reduce the increased risk for cardiovascular events and CVD-related mortality in DM,” the authors concluded.

SOURCE:

Corresponding author Alisa N. Femia, MD, of the department of dermatology at NYU Grossman School of Medicine, led the research. The study was published online in the Journal of the American Academy of Dermatology.

LIMITATIONS:

How DM treatments might influence CVD development was not addressed. EHRs may have diagnostic inaccuracies and omissions and lack data on clinical features and severity.

DISCLOSURES:

The project was supported by the National Center for Advancing Translational Sciences, National Institutes of Health. Dr. Femia reported consulting fees from Octagon Therapeutics, Timber Pharmaceuticals, and Guidepoint. Study author Michael S. Garshick, MD, reported consulting fees from AbbVie and Horizon Therapeutics. The remaining authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

Medication people with type 2 diabetes use to manage their blood sugar also appears to protect their hearts and kidneys, according to a study in JAMA Network Open. 

These pills, known as sodium-glucose cotransport protein 2 (SGLT2) inhibitors, reduce the amount of blood sugar in a kidney by causing more glucose to be excreted in urine.

Chronic kidney disease (CKD) cannot be cured and often leads to renal failure. SGLT2 inhibitor drugs can help stave off this possibility. Acute kidney disease (AKD), on the other hand, is potentially reversible. It typically occurs after an acute kidney injury, lasts for up to 90 days, and can progress to CKD if left unchecked. 

“There has been a notable absence of targeted pharmacotherapy to offer protection to these patients,” said Vin-Cent Wu, MD, PhD, a nephrologist at National Taiwan University Hospital in Taipei, and an author of the study. 

For the retrospective analysis, Dr. Wu and his colleagues looked at data from more than 230,000 adults with type 2 diabetes whose health records were gathered into a research tool called the TriNetX, a global research database. Patients had been treated for AKD between 2002 and 2022. Major adverse kidney events were noted for 5 years after discharge, which were defined as events which required regular dialysis, major adverse cardiovascular events such as a heart attack or stroke, or death. 

To determine the effects of SGLT2 inhibitors, Dr. Wu and colleagues compared outcomes among 5317 patients with AKD who received the drugs with 5317 similar patients who did not. Members of both groups had lived for at least 90 days after being discharged from the hospital and did not require dialysis during that period. 

After a median follow-up of 2.3 years, more patients who did not receive an SGLT2 inhibitor had died (994 compared with 481) or had endured major stress to their kidneys (1119 compared with 504) or heart (612 compared with 295). The relative reduction in mortality risk for people in the SGLT2-inhibitor arm was 31% (adjusted hazard ratio, 0.69; 95% CI, 0.62-0.77).

Only 2.3% of patients with AKD in the study were prescribed an SGLT2 inhibitor. 

In the United States, approximately 20% of people with type 2 diabetes and CKD receive a SGLT2 inhibitor, according to 2023 research.

“Our study reveals that the prescription rate of SGLT2 inhibitors remains relatively low in clinical practice among patients with type 2 diabetes and AKD,” Dr. Wu told this news organization. “This underscores the need for increased awareness and greater consideration of this critical issue in clinical decision-making.” 

Dr. Wu said that AKD management tends to be conservative and relies on symptom monitoring. He acknowledged that confounders may have influenced the results, and that the use of SGLT2 inhibitors might only be correlated with better results instead of producing a causation effect.

This point was raised by Ayodele Odutayo, MD, DPhil, a nephrologist at the University of Toronto, who was not involved in the study. But despite that caution, Dr. Odutayo said that he found the study to be encouraging overall and broadly in line with known benefits of SGLT2 inhibitors in CKD. 

“The findings are reassuring that the medications work even in people who’ve already had some kidney injury beforehand,” but who are not yet diagnosed with CKD, Dr. Odutayo said. 

“There is vast underuse of these medications in people for whom they are indicated,” perhaps due to clinician concern that the drugs will cause side effects such as low blood pressure or loss of salt and fluid, Dr. Odutayo said. Though those concerns are valid, the benefits of these drugs exceed the risks for most patients with CKD. 

Dr. Wu and Dr. Odutayo report no relevant financial relationships.

A version of this article appeared on Medscape.com.

Medication people with type 2 diabetes use to manage their blood sugar also appears to protect their hearts and kidneys, according to a study in JAMA Network Open. 

These pills, known as sodium-glucose cotransport protein 2 (SGLT2) inhibitors, reduce the amount of blood sugar in a kidney by causing more glucose to be excreted in urine.

Chronic kidney disease (CKD) cannot be cured and often leads to renal failure. SGLT2 inhibitor drugs can help stave off this possibility. Acute kidney disease (AKD), on the other hand, is potentially reversible. It typically occurs after an acute kidney injury, lasts for up to 90 days, and can progress to CKD if left unchecked. 

“There has been a notable absence of targeted pharmacotherapy to offer protection to these patients,” said Vin-Cent Wu, MD, PhD, a nephrologist at National Taiwan University Hospital in Taipei, and an author of the study. 

For the retrospective analysis, Dr. Wu and his colleagues looked at data from more than 230,000 adults with type 2 diabetes whose health records were gathered into a research tool called the TriNetX, a global research database. Patients had been treated for AKD between 2002 and 2022. Major adverse kidney events were noted for 5 years after discharge, which were defined as events which required regular dialysis, major adverse cardiovascular events such as a heart attack or stroke, or death. 

To determine the effects of SGLT2 inhibitors, Dr. Wu and colleagues compared outcomes among 5317 patients with AKD who received the drugs with 5317 similar patients who did not. Members of both groups had lived for at least 90 days after being discharged from the hospital and did not require dialysis during that period. 

After a median follow-up of 2.3 years, more patients who did not receive an SGLT2 inhibitor had died (994 compared with 481) or had endured major stress to their kidneys (1119 compared with 504) or heart (612 compared with 295). The relative reduction in mortality risk for people in the SGLT2-inhibitor arm was 31% (adjusted hazard ratio, 0.69; 95% CI, 0.62-0.77).

Only 2.3% of patients with AKD in the study were prescribed an SGLT2 inhibitor. 

In the United States, approximately 20% of people with type 2 diabetes and CKD receive a SGLT2 inhibitor, according to 2023 research.

“Our study reveals that the prescription rate of SGLT2 inhibitors remains relatively low in clinical practice among patients with type 2 diabetes and AKD,” Dr. Wu told this news organization. “This underscores the need for increased awareness and greater consideration of this critical issue in clinical decision-making.” 

Dr. Wu said that AKD management tends to be conservative and relies on symptom monitoring. He acknowledged that confounders may have influenced the results, and that the use of SGLT2 inhibitors might only be correlated with better results instead of producing a causation effect.

This point was raised by Ayodele Odutayo, MD, DPhil, a nephrologist at the University of Toronto, who was not involved in the study. But despite that caution, Dr. Odutayo said that he found the study to be encouraging overall and broadly in line with known benefits of SGLT2 inhibitors in CKD. 

“The findings are reassuring that the medications work even in people who’ve already had some kidney injury beforehand,” but who are not yet diagnosed with CKD, Dr. Odutayo said. 

“There is vast underuse of these medications in people for whom they are indicated,” perhaps due to clinician concern that the drugs will cause side effects such as low blood pressure or loss of salt and fluid, Dr. Odutayo said. Though those concerns are valid, the benefits of these drugs exceed the risks for most patients with CKD. 

Dr. Wu and Dr. Odutayo report no relevant financial relationships.

A version of this article appeared on Medscape.com.

Medication people with type 2 diabetes use to manage their blood sugar also appears to protect their hearts and kidneys, according to a study in JAMA Network Open. 

These pills, known as sodium-glucose cotransport protein 2 (SGLT2) inhibitors, reduce the amount of blood sugar in a kidney by causing more glucose to be excreted in urine.

Chronic kidney disease (CKD) cannot be cured and often leads to renal failure. SGLT2 inhibitor drugs can help stave off this possibility. Acute kidney disease (AKD), on the other hand, is potentially reversible. It typically occurs after an acute kidney injury, lasts for up to 90 days, and can progress to CKD if left unchecked. 

“There has been a notable absence of targeted pharmacotherapy to offer protection to these patients,” said Vin-Cent Wu, MD, PhD, a nephrologist at National Taiwan University Hospital in Taipei, and an author of the study. 

For the retrospective analysis, Dr. Wu and his colleagues looked at data from more than 230,000 adults with type 2 diabetes whose health records were gathered into a research tool called the TriNetX, a global research database. Patients had been treated for AKD between 2002 and 2022. Major adverse kidney events were noted for 5 years after discharge, which were defined as events which required regular dialysis, major adverse cardiovascular events such as a heart attack or stroke, or death. 

To determine the effects of SGLT2 inhibitors, Dr. Wu and colleagues compared outcomes among 5317 patients with AKD who received the drugs with 5317 similar patients who did not. Members of both groups had lived for at least 90 days after being discharged from the hospital and did not require dialysis during that period. 

After a median follow-up of 2.3 years, more patients who did not receive an SGLT2 inhibitor had died (994 compared with 481) or had endured major stress to their kidneys (1119 compared with 504) or heart (612 compared with 295). The relative reduction in mortality risk for people in the SGLT2-inhibitor arm was 31% (adjusted hazard ratio, 0.69; 95% CI, 0.62-0.77).

Only 2.3% of patients with AKD in the study were prescribed an SGLT2 inhibitor. 

In the United States, approximately 20% of people with type 2 diabetes and CKD receive a SGLT2 inhibitor, according to 2023 research.

“Our study reveals that the prescription rate of SGLT2 inhibitors remains relatively low in clinical practice among patients with type 2 diabetes and AKD,” Dr. Wu told this news organization. “This underscores the need for increased awareness and greater consideration of this critical issue in clinical decision-making.” 

Dr. Wu said that AKD management tends to be conservative and relies on symptom monitoring. He acknowledged that confounders may have influenced the results, and that the use of SGLT2 inhibitors might only be correlated with better results instead of producing a causation effect.

This point was raised by Ayodele Odutayo, MD, DPhil, a nephrologist at the University of Toronto, who was not involved in the study. But despite that caution, Dr. Odutayo said that he found the study to be encouraging overall and broadly in line with known benefits of SGLT2 inhibitors in CKD. 

“The findings are reassuring that the medications work even in people who’ve already had some kidney injury beforehand,” but who are not yet diagnosed with CKD, Dr. Odutayo said. 

“There is vast underuse of these medications in people for whom they are indicated,” perhaps due to clinician concern that the drugs will cause side effects such as low blood pressure or loss of salt and fluid, Dr. Odutayo said. Though those concerns are valid, the benefits of these drugs exceed the risks for most patients with CKD. 

Dr. Wu and Dr. Odutayo report no relevant financial relationships.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

The first time I saw a patient in the hospital was in 2004, twenty years ago, when I was a third-year med student. I mean, look at that guy. The things I could tell him.

Since that time, I have spent countless hours in the hospital as a resident, a renal fellow, and finally as an attending. And I’m sure many of you in the medical community feel the same thing I do, which is that patients are much more complicated now than they used to be. I’ll listen to an intern present a new case on rounds and she’ll have an assessment and plan that encompasses a dozen individual medical problems. Sometimes I have to literally be like, “Wait, why is this patient here again?”

But until now, I had no data to convince myself that this feeling was real — that hospitalized patients are getting more and more complicated, or that they only seem more complicated because I’m getting older. Maybe I was better able to keep track of things when I was an intern rather than now as an attending, spending just a couple months of the year in the hospital. I mean, after all, if patients were getting more complicated, surely hospitals would know this and allocate more resources to patient care, right?

Right?

It’s not an illusion. At least not according to this paper, Population-Based Trends in Complexity of Hospital Inpatients, appearing in JAMA Internal Medicine, which examines about 15 years of inpatient hospital admissions in British Columbia.

I like Canada for this study for two reasons: First, their electronic health record system is province-wide, so they don’t have issues of getting data from hospital A vs hospital B. All the data are there — in this case, more than 3 million nonelective hospital admissions from British Columbia. Second, there is universal healthcare. We don’t have to worry about insurance companies changing, or the start of a new program like the Affordable Care Act. It’s just a cleaner set-up.

Of course, complexity is hard to define, and the authors here decide to look at a variety of metrics I think we can agree are tied into complexity. These include things like patient age, comorbidities, medications, frequency of hospitalization, and so on. They also looked at outcomes associated with hospitalization: Did the patient require the ICU? Did they survive? Were they readmitted?

And the tale of the tape is as clear as that British Columbian air: Over the past 15 years, your average hospitalized patient is about 3 years older, is twice as likely to have kidney disease, 70% more likely to have diabetes, is on more medications (particularly anticoagulants), and is much more likely to be admitted through the emergency room. They’ve also spent more time in the hospital in the past year.

Given the increased complexity, you might expect that the outcomes for these patients are worse than years ago, but the data do not bear that out. In fact, inpatient mortality is lower now than it was 15 years ago, although 30-day postdischarge mortality is higher. Put those together and it turns out that death rates are pretty stable: 9% of people admitted for nonelective reasons to the hospital will die within 30 days. It’s just that nowadays, we tend to discharge them before that happens.

Why are our patients getting more complex? Some of it is demographics; the population is aging, after all. Some of it relates to the increasing burden of comorbidities like diabetes and kidney disease, which are associated with the obesity epidemic. But in some ways, we’re a victim of our own success. We have the ability to keep people alive today who would not have survived 15 years ago. We have better treatments for metastatic cancer, less-invasive therapies for heart disease, better protocolized ICU care.

Given all that, does it make any sense that many of our hospitals are at skeleton-crew staffing levels? That hospitalists report taking care of more patients than they ever have before?

There’s been so much talk about burnout in the health professions lately. Maybe something people need to start acknowledging — particularly those who haven’t practiced on the front lines for a decade or two — is that the job is, quite simply, harder now. As patients become more complex, we need more resources, human and otherwise, to care for them.

F. Perry Wilson, MD, MSCE, is an associate professor of medicine and public health and director of Yale’s Clinical and Translational Research Accelerator. His science communication work can be found in the Huffington Post, on NPR, and here on Medscape. He tweets @fperrywilson and his book, How Medicine Works and When It Doesn’t, is available now. He has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

The first time I saw a patient in the hospital was in 2004, twenty years ago, when I was a third-year med student. I mean, look at that guy. The things I could tell him.

Since that time, I have spent countless hours in the hospital as a resident, a renal fellow, and finally as an attending. And I’m sure many of you in the medical community feel the same thing I do, which is that patients are much more complicated now than they used to be. I’ll listen to an intern present a new case on rounds and she’ll have an assessment and plan that encompasses a dozen individual medical problems. Sometimes I have to literally be like, “Wait, why is this patient here again?”

But until now, I had no data to convince myself that this feeling was real — that hospitalized patients are getting more and more complicated, or that they only seem more complicated because I’m getting older. Maybe I was better able to keep track of things when I was an intern rather than now as an attending, spending just a couple months of the year in the hospital. I mean, after all, if patients were getting more complicated, surely hospitals would know this and allocate more resources to patient care, right?

Right?

It’s not an illusion. At least not according to this paper, Population-Based Trends in Complexity of Hospital Inpatients, appearing in JAMA Internal Medicine, which examines about 15 years of inpatient hospital admissions in British Columbia.

I like Canada for this study for two reasons: First, their electronic health record system is province-wide, so they don’t have issues of getting data from hospital A vs hospital B. All the data are there — in this case, more than 3 million nonelective hospital admissions from British Columbia. Second, there is universal healthcare. We don’t have to worry about insurance companies changing, or the start of a new program like the Affordable Care Act. It’s just a cleaner set-up.

Of course, complexity is hard to define, and the authors here decide to look at a variety of metrics I think we can agree are tied into complexity. These include things like patient age, comorbidities, medications, frequency of hospitalization, and so on. They also looked at outcomes associated with hospitalization: Did the patient require the ICU? Did they survive? Were they readmitted?

And the tale of the tape is as clear as that British Columbian air: Over the past 15 years, your average hospitalized patient is about 3 years older, is twice as likely to have kidney disease, 70% more likely to have diabetes, is on more medications (particularly anticoagulants), and is much more likely to be admitted through the emergency room. They’ve also spent more time in the hospital in the past year.

Given the increased complexity, you might expect that the outcomes for these patients are worse than years ago, but the data do not bear that out. In fact, inpatient mortality is lower now than it was 15 years ago, although 30-day postdischarge mortality is higher. Put those together and it turns out that death rates are pretty stable: 9% of people admitted for nonelective reasons to the hospital will die within 30 days. It’s just that nowadays, we tend to discharge them before that happens.

Why are our patients getting more complex? Some of it is demographics; the population is aging, after all. Some of it relates to the increasing burden of comorbidities like diabetes and kidney disease, which are associated with the obesity epidemic. But in some ways, we’re a victim of our own success. We have the ability to keep people alive today who would not have survived 15 years ago. We have better treatments for metastatic cancer, less-invasive therapies for heart disease, better protocolized ICU care.

Given all that, does it make any sense that many of our hospitals are at skeleton-crew staffing levels? That hospitalists report taking care of more patients than they ever have before?

There’s been so much talk about burnout in the health professions lately. Maybe something people need to start acknowledging — particularly those who haven’t practiced on the front lines for a decade or two — is that the job is, quite simply, harder now. As patients become more complex, we need more resources, human and otherwise, to care for them.

F. Perry Wilson, MD, MSCE, is an associate professor of medicine and public health and director of Yale’s Clinical and Translational Research Accelerator. His science communication work can be found in the Huffington Post, on NPR, and here on Medscape. He tweets @fperrywilson and his book, How Medicine Works and When It Doesn’t, is available now. He has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

The first time I saw a patient in the hospital was in 2004, twenty years ago, when I was a third-year med student. I mean, look at that guy. The things I could tell him.

Since that time, I have spent countless hours in the hospital as a resident, a renal fellow, and finally as an attending. And I’m sure many of you in the medical community feel the same thing I do, which is that patients are much more complicated now than they used to be. I’ll listen to an intern present a new case on rounds and she’ll have an assessment and plan that encompasses a dozen individual medical problems. Sometimes I have to literally be like, “Wait, why is this patient here again?”

But until now, I had no data to convince myself that this feeling was real — that hospitalized patients are getting more and more complicated, or that they only seem more complicated because I’m getting older. Maybe I was better able to keep track of things when I was an intern rather than now as an attending, spending just a couple months of the year in the hospital. I mean, after all, if patients were getting more complicated, surely hospitals would know this and allocate more resources to patient care, right?

Right?

It’s not an illusion. At least not according to this paper, Population-Based Trends in Complexity of Hospital Inpatients, appearing in JAMA Internal Medicine, which examines about 15 years of inpatient hospital admissions in British Columbia.

I like Canada for this study for two reasons: First, their electronic health record system is province-wide, so they don’t have issues of getting data from hospital A vs hospital B. All the data are there — in this case, more than 3 million nonelective hospital admissions from British Columbia. Second, there is universal healthcare. We don’t have to worry about insurance companies changing, or the start of a new program like the Affordable Care Act. It’s just a cleaner set-up.

Of course, complexity is hard to define, and the authors here decide to look at a variety of metrics I think we can agree are tied into complexity. These include things like patient age, comorbidities, medications, frequency of hospitalization, and so on. They also looked at outcomes associated with hospitalization: Did the patient require the ICU? Did they survive? Were they readmitted?

And the tale of the tape is as clear as that British Columbian air: Over the past 15 years, your average hospitalized patient is about 3 years older, is twice as likely to have kidney disease, 70% more likely to have diabetes, is on more medications (particularly anticoagulants), and is much more likely to be admitted through the emergency room. They’ve also spent more time in the hospital in the past year.

Given the increased complexity, you might expect that the outcomes for these patients are worse than years ago, but the data do not bear that out. In fact, inpatient mortality is lower now than it was 15 years ago, although 30-day postdischarge mortality is higher. Put those together and it turns out that death rates are pretty stable: 9% of people admitted for nonelective reasons to the hospital will die within 30 days. It’s just that nowadays, we tend to discharge them before that happens.

Why are our patients getting more complex? Some of it is demographics; the population is aging, after all. Some of it relates to the increasing burden of comorbidities like diabetes and kidney disease, which are associated with the obesity epidemic. But in some ways, we’re a victim of our own success. We have the ability to keep people alive today who would not have survived 15 years ago. We have better treatments for metastatic cancer, less-invasive therapies for heart disease, better protocolized ICU care.

Given all that, does it make any sense that many of our hospitals are at skeleton-crew staffing levels? That hospitalists report taking care of more patients than they ever have before?

There’s been so much talk about burnout in the health professions lately. Maybe something people need to start acknowledging — particularly those who haven’t practiced on the front lines for a decade or two — is that the job is, quite simply, harder now. As patients become more complex, we need more resources, human and otherwise, to care for them.

F. Perry Wilson, MD, MSCE, is an associate professor of medicine and public health and director of Yale’s Clinical and Translational Research Accelerator. His science communication work can be found in the Huffington Post, on NPR, and here on Medscape. He tweets @fperrywilson and his book, How Medicine Works and When It Doesn’t, is available now. He has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.