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FDA okays Tidepool Loop app to help guide insulin delivery
The Food and Drug Administration has cleared the Tidepool Loop, a mobile application for use with compatible continuous glucose monitors (CGMs) and insulin pumps to enable automated insulin delivery.
Indicated for people with type 1 diabetes ages 6 years and up, the app algorithm was developed by the diabetes startup Tidepool, which already hosts a cloud-based platform for users to download and review data from different glucose meters, insulin pumps, and CGM systems. The Tidepool Loop project arose from patient-led, open-source initiatives to enable interoperability between the devices.
“The [FDA] authorization of the Tidepool Loop is a huge win for the type 1 diabetes (T1D) community and is a vital step towards a world where people with T1D can choose the pump, CGM, and algorithm that are best for them – and have all three work together seamlessly,” Aaron Kowalski, PhD, CEO of the advocacy organization JDRF, said in a statement.
JDRF helped support preclinical and clinical research in the development of the Loop algorithm, along with The Leona M. and Harry B. Helmsley Charitable Trust, the Tullman Foundation, and partnerships with device makers and donations from the T1D community.
Available by prescription only, the Tidepool app is for single patient use. It works with designated “integrated CGMs” and “alternate controller enabled pumps” to automatically increase, decrease, or suspend insulin delivery, based on the glucose readings and predicted values. The app can also recommend correction doses, which the user can confirm.
According to an FDA statement:“Tidepool Loop’s algorithm technology is designed to be compatible with other individual interoperable devices that meet prespecified acceptance criteria set forth in a validation and integration plan provided by the sponsor and cleared by the FDA as part of the premarket submission.”
Tidepool is finalizing agreements with the various device manufacturers “to create a seamless experience for both physicians prescribing Tidepool Loop and the patients using it,” according to a company statement.
Tidepool’s initial launch device partners have not yet been announced, but the company “has a development partnership with Dexcom and other yet-to-be-named medical device companies for future inclusion of their components with the Tidepool Loop platform,” the statement says.
A version of this article first appeared on Medscape.com.
The Food and Drug Administration has cleared the Tidepool Loop, a mobile application for use with compatible continuous glucose monitors (CGMs) and insulin pumps to enable automated insulin delivery.
Indicated for people with type 1 diabetes ages 6 years and up, the app algorithm was developed by the diabetes startup Tidepool, which already hosts a cloud-based platform for users to download and review data from different glucose meters, insulin pumps, and CGM systems. The Tidepool Loop project arose from patient-led, open-source initiatives to enable interoperability between the devices.
“The [FDA] authorization of the Tidepool Loop is a huge win for the type 1 diabetes (T1D) community and is a vital step towards a world where people with T1D can choose the pump, CGM, and algorithm that are best for them – and have all three work together seamlessly,” Aaron Kowalski, PhD, CEO of the advocacy organization JDRF, said in a statement.
JDRF helped support preclinical and clinical research in the development of the Loop algorithm, along with The Leona M. and Harry B. Helmsley Charitable Trust, the Tullman Foundation, and partnerships with device makers and donations from the T1D community.
Available by prescription only, the Tidepool app is for single patient use. It works with designated “integrated CGMs” and “alternate controller enabled pumps” to automatically increase, decrease, or suspend insulin delivery, based on the glucose readings and predicted values. The app can also recommend correction doses, which the user can confirm.
According to an FDA statement:“Tidepool Loop’s algorithm technology is designed to be compatible with other individual interoperable devices that meet prespecified acceptance criteria set forth in a validation and integration plan provided by the sponsor and cleared by the FDA as part of the premarket submission.”
Tidepool is finalizing agreements with the various device manufacturers “to create a seamless experience for both physicians prescribing Tidepool Loop and the patients using it,” according to a company statement.
Tidepool’s initial launch device partners have not yet been announced, but the company “has a development partnership with Dexcom and other yet-to-be-named medical device companies for future inclusion of their components with the Tidepool Loop platform,” the statement says.
A version of this article first appeared on Medscape.com.
The Food and Drug Administration has cleared the Tidepool Loop, a mobile application for use with compatible continuous glucose monitors (CGMs) and insulin pumps to enable automated insulin delivery.
Indicated for people with type 1 diabetes ages 6 years and up, the app algorithm was developed by the diabetes startup Tidepool, which already hosts a cloud-based platform for users to download and review data from different glucose meters, insulin pumps, and CGM systems. The Tidepool Loop project arose from patient-led, open-source initiatives to enable interoperability between the devices.
“The [FDA] authorization of the Tidepool Loop is a huge win for the type 1 diabetes (T1D) community and is a vital step towards a world where people with T1D can choose the pump, CGM, and algorithm that are best for them – and have all three work together seamlessly,” Aaron Kowalski, PhD, CEO of the advocacy organization JDRF, said in a statement.
JDRF helped support preclinical and clinical research in the development of the Loop algorithm, along with The Leona M. and Harry B. Helmsley Charitable Trust, the Tullman Foundation, and partnerships with device makers and donations from the T1D community.
Available by prescription only, the Tidepool app is for single patient use. It works with designated “integrated CGMs” and “alternate controller enabled pumps” to automatically increase, decrease, or suspend insulin delivery, based on the glucose readings and predicted values. The app can also recommend correction doses, which the user can confirm.
According to an FDA statement:“Tidepool Loop’s algorithm technology is designed to be compatible with other individual interoperable devices that meet prespecified acceptance criteria set forth in a validation and integration plan provided by the sponsor and cleared by the FDA as part of the premarket submission.”
Tidepool is finalizing agreements with the various device manufacturers “to create a seamless experience for both physicians prescribing Tidepool Loop and the patients using it,” according to a company statement.
Tidepool’s initial launch device partners have not yet been announced, but the company “has a development partnership with Dexcom and other yet-to-be-named medical device companies for future inclusion of their components with the Tidepool Loop platform,” the statement says.
A version of this article first appeared on Medscape.com.
FDA approves new type 2 diabetes drug bexagliflozin
The U.S. Food and Drug Administration has approved bexagliflozin (Brenzavvy, TheracosBio) for the treatment of adults with type 2 diabetes.
The once-daily 20-mg oral sodium-glucose cotransporter 2 (SGLT2) inhibitor is indicated as an adjunct to diet and exercise to improve glycemic control for those with type 2 diabetes, but not type 1 diabetes. It can be used in adults with an estimated glomerular filtration rate (eGFR) > 30 mL/min per 1.73 m2.
Approval was based on results from 23 clinical trials with more than 5,000 participants, including more than 300 patients with stage 3 kidney disease (eGFR < 60 and > 30 mL/min per 1.73 m2).
In the phase 3 studies, bexagliflozin significantly reduced hemoglobin A1c and fasting blood glucose at 24 weeks as monotherapy or as add-on to metformin and other glucose-lowering drugs and combinations. It also produced modest reductions in body weight and systolic blood pressure.
In the phase 3 Bexagliflozin Efficacy and Safety Trial (BEST) cardiovascular outcomes trial, the drug met its efficacy and safety objectives in patients at high cardiovascular risk. Noninferiority was demonstrated for the composite outcome of cardiovascular death, myocardial infarction, stroke, or unstable angina.
“As a class of drugs, SGLT2 inhibitors have shown tremendous benefit in treating adults with type 2 diabetes,” said Mason Freeman, MD, director of the Translational Research Center at Massachusetts General Hospital, Boston, in a press release from TheracosBio.
“Being involved in all of the clinical trials for Brenzavvy, I am greatly impressed with the efficacy of the drug in reducing blood glucose levels and I believe it is an important addition to the SGLT2 inhibitor class of drugs.”
As with other SGLT2 inhibitors, adverse events seen in the trials include ketoacidosis, lower limb amputation, volume depletion, urosepsis, pyelonephritis, Fournier’s gangrene, genital mycotic infections, and hypoglycemia when used with insulin or insulin secretagogues.
Bexagliflozin joins an already crowded field of SGLT2 inhibitors, some of which have been approved for additional cardiovascular and kidney indications.
Of interest, bexagliflozin was approved by the FDA for diabetes in cats in December 2022, as the first oral new animal drug to improve glycemic control in otherwise healthy cats with diabetes not previously treated with insulin.
A version of this article first appeared on Medscape.com.
The U.S. Food and Drug Administration has approved bexagliflozin (Brenzavvy, TheracosBio) for the treatment of adults with type 2 diabetes.
The once-daily 20-mg oral sodium-glucose cotransporter 2 (SGLT2) inhibitor is indicated as an adjunct to diet and exercise to improve glycemic control for those with type 2 diabetes, but not type 1 diabetes. It can be used in adults with an estimated glomerular filtration rate (eGFR) > 30 mL/min per 1.73 m2.
Approval was based on results from 23 clinical trials with more than 5,000 participants, including more than 300 patients with stage 3 kidney disease (eGFR < 60 and > 30 mL/min per 1.73 m2).
In the phase 3 studies, bexagliflozin significantly reduced hemoglobin A1c and fasting blood glucose at 24 weeks as monotherapy or as add-on to metformin and other glucose-lowering drugs and combinations. It also produced modest reductions in body weight and systolic blood pressure.
In the phase 3 Bexagliflozin Efficacy and Safety Trial (BEST) cardiovascular outcomes trial, the drug met its efficacy and safety objectives in patients at high cardiovascular risk. Noninferiority was demonstrated for the composite outcome of cardiovascular death, myocardial infarction, stroke, or unstable angina.
“As a class of drugs, SGLT2 inhibitors have shown tremendous benefit in treating adults with type 2 diabetes,” said Mason Freeman, MD, director of the Translational Research Center at Massachusetts General Hospital, Boston, in a press release from TheracosBio.
“Being involved in all of the clinical trials for Brenzavvy, I am greatly impressed with the efficacy of the drug in reducing blood glucose levels and I believe it is an important addition to the SGLT2 inhibitor class of drugs.”
As with other SGLT2 inhibitors, adverse events seen in the trials include ketoacidosis, lower limb amputation, volume depletion, urosepsis, pyelonephritis, Fournier’s gangrene, genital mycotic infections, and hypoglycemia when used with insulin or insulin secretagogues.
Bexagliflozin joins an already crowded field of SGLT2 inhibitors, some of which have been approved for additional cardiovascular and kidney indications.
Of interest, bexagliflozin was approved by the FDA for diabetes in cats in December 2022, as the first oral new animal drug to improve glycemic control in otherwise healthy cats with diabetes not previously treated with insulin.
A version of this article first appeared on Medscape.com.
The U.S. Food and Drug Administration has approved bexagliflozin (Brenzavvy, TheracosBio) for the treatment of adults with type 2 diabetes.
The once-daily 20-mg oral sodium-glucose cotransporter 2 (SGLT2) inhibitor is indicated as an adjunct to diet and exercise to improve glycemic control for those with type 2 diabetes, but not type 1 diabetes. It can be used in adults with an estimated glomerular filtration rate (eGFR) > 30 mL/min per 1.73 m2.
Approval was based on results from 23 clinical trials with more than 5,000 participants, including more than 300 patients with stage 3 kidney disease (eGFR < 60 and > 30 mL/min per 1.73 m2).
In the phase 3 studies, bexagliflozin significantly reduced hemoglobin A1c and fasting blood glucose at 24 weeks as monotherapy or as add-on to metformin and other glucose-lowering drugs and combinations. It also produced modest reductions in body weight and systolic blood pressure.
In the phase 3 Bexagliflozin Efficacy and Safety Trial (BEST) cardiovascular outcomes trial, the drug met its efficacy and safety objectives in patients at high cardiovascular risk. Noninferiority was demonstrated for the composite outcome of cardiovascular death, myocardial infarction, stroke, or unstable angina.
“As a class of drugs, SGLT2 inhibitors have shown tremendous benefit in treating adults with type 2 diabetes,” said Mason Freeman, MD, director of the Translational Research Center at Massachusetts General Hospital, Boston, in a press release from TheracosBio.
“Being involved in all of the clinical trials for Brenzavvy, I am greatly impressed with the efficacy of the drug in reducing blood glucose levels and I believe it is an important addition to the SGLT2 inhibitor class of drugs.”
As with other SGLT2 inhibitors, adverse events seen in the trials include ketoacidosis, lower limb amputation, volume depletion, urosepsis, pyelonephritis, Fournier’s gangrene, genital mycotic infections, and hypoglycemia when used with insulin or insulin secretagogues.
Bexagliflozin joins an already crowded field of SGLT2 inhibitors, some of which have been approved for additional cardiovascular and kidney indications.
Of interest, bexagliflozin was approved by the FDA for diabetes in cats in December 2022, as the first oral new animal drug to improve glycemic control in otherwise healthy cats with diabetes not previously treated with insulin.
A version of this article first appeared on Medscape.com.
Metformin monotherapy not always best start in type 2 diabetes
Metformin failure in people with type 2 diabetes is very common, particularly among those with high hemoglobin A1c levels at the time of diagnosis, new findings suggest.
An analysis of electronic health record data for more than 22,000 patients starting metformin at three U.S. clinical sites found that over 40% experienced metformin failure.
This was defined as either failure to achieve or maintain A1c less than 7% within 18 months or the use of additional glucose-lowering medications.
Other predictors that metformin use wouldn’t be successful included increasing age, male sex, and race/ethnicity. However, the latter ceased to be linked after adjustment for other clinical risk factors.
“Our study results suggest increased monitoring with potentially earlier treatment intensification to achieve glycemic control may be appropriate in patients with clinical parameters described in this paper,” Suzette J. Bielinski, PhD, and colleagues wrote.
“Further, these results call into question the ubiquitous use of metformin as the first-line therapy and suggest a more individualized approach may be needed to optimize therapy,” they added in their article, published online in the Journal of Clinical Endocrinology and Metabolism.
The study is also noteworthy in that it demonstrated the feasibility of using EHR data with a machine-learning approach to discover risk biomarkers, Dr. Bielinski, professor of epidemiology at the Mayo Clinic, Rochester, Minn., said in an interview.
“We wanted to repurpose clinical data to answer questions ... I think more studies using these types of techniques repurposing data meant for one thing could potentially impact care in other domains. ... If we can get the bang for the buck from all these data that we generate on people I just think it will improve health care and maybe save health care dollars.”
Baseline A1c strongest predictor of metformin failure
The investigators identified a total of 22,047 metformin initiators from three clinical primary care sites: the University of Mississippi’s Jackson centers, which serves a mostly African American population, the Mountain Park Health Center in Arizona, a seven-clinic federally qualified community health center in Phoenix that serves a mostly Latino population, and the Rochester Epidemiology Project, which includes the Mayo Clinic and serves a primarily White population.
Overall, a total of 43% (9,407) of patients met one of two criteria for metformin failure by 18 months. Among those, median time to failure on metformin was 3.9 months.
Unadjusted failure rates were higher among African Americans, Hispanics, and other racial groups, compared with non-Hispanic White patients.
However, the racial groups also differed by baseline characteristics. Mean A1c was 7.7% overall, 8.1% for the African American group, 7.9% for Asians, and 8.2% for Hispanics, compared with 7.6% for non-Hispanic Whites.
Of 150 clinical factors examined, higher A1c was the strongest predictor of metformin failure, with a rapid increase in risk appearing between 7.5% and 8.0%.
“The slope is steep. It gives us some clinical guidance,” Dr. Bielinski said.
Other variables positively correlated with metformin failure included “diabetes with complications,” increased age, and higher levels of potassium, triglycerides, heart rate, and mean cell hemoglobin.
Factors inversely correlated with metformin failure were having received screening for other suspected conditions and medical examination/evaluation, and lower levels of sodium, albumin, and HDL cholesterol.
Three variables – body mass index, LDL cholesterol, and creatinine – had a U-shaped relationship with metformin failure, so that both high and low values were associated with increased risk.
“The racial/ethnic differences disappeared once other clinical factors were considered suggesting that the biological response to metformin is similar regardless of race/ethnicity,” Dr. Bielinski and colleagues wrote.
They also noted that the abnormal lab results which correlated with metformin failure “likely represent biomarkers for chronic illnesses. However, the effect size for lab abnormalities was small compared with that of baseline A1c.”
Dr. Bielinski urged caution in interpreting the findings. “Electronic health records data have limitations. We have evidence that these people were prescribed metformin. We have no idea if they took it. ... I would really be hesitant to be too strong in making clinical recommendations.”
However, she said that the data are “suggestive to say maybe we need to have some kind of threshold where if someone comes in with an A1c of X that they go on dual therapy right away. I think this is opening the door to that.”
The authors reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Metformin failure in people with type 2 diabetes is very common, particularly among those with high hemoglobin A1c levels at the time of diagnosis, new findings suggest.
An analysis of electronic health record data for more than 22,000 patients starting metformin at three U.S. clinical sites found that over 40% experienced metformin failure.
This was defined as either failure to achieve or maintain A1c less than 7% within 18 months or the use of additional glucose-lowering medications.
Other predictors that metformin use wouldn’t be successful included increasing age, male sex, and race/ethnicity. However, the latter ceased to be linked after adjustment for other clinical risk factors.
“Our study results suggest increased monitoring with potentially earlier treatment intensification to achieve glycemic control may be appropriate in patients with clinical parameters described in this paper,” Suzette J. Bielinski, PhD, and colleagues wrote.
“Further, these results call into question the ubiquitous use of metformin as the first-line therapy and suggest a more individualized approach may be needed to optimize therapy,” they added in their article, published online in the Journal of Clinical Endocrinology and Metabolism.
The study is also noteworthy in that it demonstrated the feasibility of using EHR data with a machine-learning approach to discover risk biomarkers, Dr. Bielinski, professor of epidemiology at the Mayo Clinic, Rochester, Minn., said in an interview.
“We wanted to repurpose clinical data to answer questions ... I think more studies using these types of techniques repurposing data meant for one thing could potentially impact care in other domains. ... If we can get the bang for the buck from all these data that we generate on people I just think it will improve health care and maybe save health care dollars.”
Baseline A1c strongest predictor of metformin failure
The investigators identified a total of 22,047 metformin initiators from three clinical primary care sites: the University of Mississippi’s Jackson centers, which serves a mostly African American population, the Mountain Park Health Center in Arizona, a seven-clinic federally qualified community health center in Phoenix that serves a mostly Latino population, and the Rochester Epidemiology Project, which includes the Mayo Clinic and serves a primarily White population.
Overall, a total of 43% (9,407) of patients met one of two criteria for metformin failure by 18 months. Among those, median time to failure on metformin was 3.9 months.
Unadjusted failure rates were higher among African Americans, Hispanics, and other racial groups, compared with non-Hispanic White patients.
However, the racial groups also differed by baseline characteristics. Mean A1c was 7.7% overall, 8.1% for the African American group, 7.9% for Asians, and 8.2% for Hispanics, compared with 7.6% for non-Hispanic Whites.
Of 150 clinical factors examined, higher A1c was the strongest predictor of metformin failure, with a rapid increase in risk appearing between 7.5% and 8.0%.
“The slope is steep. It gives us some clinical guidance,” Dr. Bielinski said.
Other variables positively correlated with metformin failure included “diabetes with complications,” increased age, and higher levels of potassium, triglycerides, heart rate, and mean cell hemoglobin.
Factors inversely correlated with metformin failure were having received screening for other suspected conditions and medical examination/evaluation, and lower levels of sodium, albumin, and HDL cholesterol.
Three variables – body mass index, LDL cholesterol, and creatinine – had a U-shaped relationship with metformin failure, so that both high and low values were associated with increased risk.
“The racial/ethnic differences disappeared once other clinical factors were considered suggesting that the biological response to metformin is similar regardless of race/ethnicity,” Dr. Bielinski and colleagues wrote.
They also noted that the abnormal lab results which correlated with metformin failure “likely represent biomarkers for chronic illnesses. However, the effect size for lab abnormalities was small compared with that of baseline A1c.”
Dr. Bielinski urged caution in interpreting the findings. “Electronic health records data have limitations. We have evidence that these people were prescribed metformin. We have no idea if they took it. ... I would really be hesitant to be too strong in making clinical recommendations.”
However, she said that the data are “suggestive to say maybe we need to have some kind of threshold where if someone comes in with an A1c of X that they go on dual therapy right away. I think this is opening the door to that.”
The authors reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Metformin failure in people with type 2 diabetes is very common, particularly among those with high hemoglobin A1c levels at the time of diagnosis, new findings suggest.
An analysis of electronic health record data for more than 22,000 patients starting metformin at three U.S. clinical sites found that over 40% experienced metformin failure.
This was defined as either failure to achieve or maintain A1c less than 7% within 18 months or the use of additional glucose-lowering medications.
Other predictors that metformin use wouldn’t be successful included increasing age, male sex, and race/ethnicity. However, the latter ceased to be linked after adjustment for other clinical risk factors.
“Our study results suggest increased monitoring with potentially earlier treatment intensification to achieve glycemic control may be appropriate in patients with clinical parameters described in this paper,” Suzette J. Bielinski, PhD, and colleagues wrote.
“Further, these results call into question the ubiquitous use of metformin as the first-line therapy and suggest a more individualized approach may be needed to optimize therapy,” they added in their article, published online in the Journal of Clinical Endocrinology and Metabolism.
The study is also noteworthy in that it demonstrated the feasibility of using EHR data with a machine-learning approach to discover risk biomarkers, Dr. Bielinski, professor of epidemiology at the Mayo Clinic, Rochester, Minn., said in an interview.
“We wanted to repurpose clinical data to answer questions ... I think more studies using these types of techniques repurposing data meant for one thing could potentially impact care in other domains. ... If we can get the bang for the buck from all these data that we generate on people I just think it will improve health care and maybe save health care dollars.”
Baseline A1c strongest predictor of metformin failure
The investigators identified a total of 22,047 metformin initiators from three clinical primary care sites: the University of Mississippi’s Jackson centers, which serves a mostly African American population, the Mountain Park Health Center in Arizona, a seven-clinic federally qualified community health center in Phoenix that serves a mostly Latino population, and the Rochester Epidemiology Project, which includes the Mayo Clinic and serves a primarily White population.
Overall, a total of 43% (9,407) of patients met one of two criteria for metformin failure by 18 months. Among those, median time to failure on metformin was 3.9 months.
Unadjusted failure rates were higher among African Americans, Hispanics, and other racial groups, compared with non-Hispanic White patients.
However, the racial groups also differed by baseline characteristics. Mean A1c was 7.7% overall, 8.1% for the African American group, 7.9% for Asians, and 8.2% for Hispanics, compared with 7.6% for non-Hispanic Whites.
Of 150 clinical factors examined, higher A1c was the strongest predictor of metformin failure, with a rapid increase in risk appearing between 7.5% and 8.0%.
“The slope is steep. It gives us some clinical guidance,” Dr. Bielinski said.
Other variables positively correlated with metformin failure included “diabetes with complications,” increased age, and higher levels of potassium, triglycerides, heart rate, and mean cell hemoglobin.
Factors inversely correlated with metformin failure were having received screening for other suspected conditions and medical examination/evaluation, and lower levels of sodium, albumin, and HDL cholesterol.
Three variables – body mass index, LDL cholesterol, and creatinine – had a U-shaped relationship with metformin failure, so that both high and low values were associated with increased risk.
“The racial/ethnic differences disappeared once other clinical factors were considered suggesting that the biological response to metformin is similar regardless of race/ethnicity,” Dr. Bielinski and colleagues wrote.
They also noted that the abnormal lab results which correlated with metformin failure “likely represent biomarkers for chronic illnesses. However, the effect size for lab abnormalities was small compared with that of baseline A1c.”
Dr. Bielinski urged caution in interpreting the findings. “Electronic health records data have limitations. We have evidence that these people were prescribed metformin. We have no idea if they took it. ... I would really be hesitant to be too strong in making clinical recommendations.”
However, she said that the data are “suggestive to say maybe we need to have some kind of threshold where if someone comes in with an A1c of X that they go on dual therapy right away. I think this is opening the door to that.”
The authors reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Oramed oral insulin fails to meet goal in type 2 diabetes
Oramed Pharmaceuticals’ investigational oral insulin failed to achieve its primary endpoint in a phase 3 trial, according to top-line results announced by the company.
“Therefore, Oramed expects to discontinue its oral insulin clinical activities for [type 2 diabetes],” according to a company statement.
, ORA-D-013-1, comparing the efficacy of the insulin product ORMD-0801 to placebo in 710 people with type 2 diabetes with inadequate glycemic control on two or three oral glucose-lowering agents.
The participants were randomized 2:2:1:1 into ORMD-0801 dosed at 8 mg once or twice daily, or placebo dosed once or twice daily. They completed a 21-day screening period, followed by a 26-week double-blind treatment period.
The product didn’t achieve the primary endpoint comparing reduction in hemoglobin A1c from baseline to 26 weeks, or the secondary endpoint of mean change in fasting plasma glucose at 26 weeks. There were no serious adverse events.
Oramed Pharmaceuticals specializes in developing oral delivery formulations of drugs currently delivered via injection. The company has offices in the United States and Israel.
Oramed CEO Nadav Kidron commented in the statement, “Today’s outcome is very disappointing, given the positive results from prior trials. Once full data from the studies are available, we expect to share relevant learnings and future plans. We thank all the patients, families, and health care professionals who participated in the trial.”
Insulin manufacturer Novo Nordisk had also been developing an oral insulin product. Successful phase 2a results were presented at the American Diabetes Association’s 2017 Scientific Sessions and full phase 2 feasibility results were published in Lancet Diabetes & Endocrinology in 2019.
However, Novo Nordisk, which manufactures the oral glucagon-like peptide-1 receptor agonist semaglutide (Rybelsus), subsequently discontinued development of their oral insulin product. According to a statement, “Initial results raised questions about truly addressing patients’ unmet needs with insulin therapy. Therefore, we discontinued this work to focus on projects that could in fact improve cardiometabolic outcomes for people living with diabetes.”
A version of this article first appeared on Medscape.com.
Oramed Pharmaceuticals’ investigational oral insulin failed to achieve its primary endpoint in a phase 3 trial, according to top-line results announced by the company.
“Therefore, Oramed expects to discontinue its oral insulin clinical activities for [type 2 diabetes],” according to a company statement.
, ORA-D-013-1, comparing the efficacy of the insulin product ORMD-0801 to placebo in 710 people with type 2 diabetes with inadequate glycemic control on two or three oral glucose-lowering agents.
The participants were randomized 2:2:1:1 into ORMD-0801 dosed at 8 mg once or twice daily, or placebo dosed once or twice daily. They completed a 21-day screening period, followed by a 26-week double-blind treatment period.
The product didn’t achieve the primary endpoint comparing reduction in hemoglobin A1c from baseline to 26 weeks, or the secondary endpoint of mean change in fasting plasma glucose at 26 weeks. There were no serious adverse events.
Oramed Pharmaceuticals specializes in developing oral delivery formulations of drugs currently delivered via injection. The company has offices in the United States and Israel.
Oramed CEO Nadav Kidron commented in the statement, “Today’s outcome is very disappointing, given the positive results from prior trials. Once full data from the studies are available, we expect to share relevant learnings and future plans. We thank all the patients, families, and health care professionals who participated in the trial.”
Insulin manufacturer Novo Nordisk had also been developing an oral insulin product. Successful phase 2a results were presented at the American Diabetes Association’s 2017 Scientific Sessions and full phase 2 feasibility results were published in Lancet Diabetes & Endocrinology in 2019.
However, Novo Nordisk, which manufactures the oral glucagon-like peptide-1 receptor agonist semaglutide (Rybelsus), subsequently discontinued development of their oral insulin product. According to a statement, “Initial results raised questions about truly addressing patients’ unmet needs with insulin therapy. Therefore, we discontinued this work to focus on projects that could in fact improve cardiometabolic outcomes for people living with diabetes.”
A version of this article first appeared on Medscape.com.
Oramed Pharmaceuticals’ investigational oral insulin failed to achieve its primary endpoint in a phase 3 trial, according to top-line results announced by the company.
“Therefore, Oramed expects to discontinue its oral insulin clinical activities for [type 2 diabetes],” according to a company statement.
, ORA-D-013-1, comparing the efficacy of the insulin product ORMD-0801 to placebo in 710 people with type 2 diabetes with inadequate glycemic control on two or three oral glucose-lowering agents.
The participants were randomized 2:2:1:1 into ORMD-0801 dosed at 8 mg once or twice daily, or placebo dosed once or twice daily. They completed a 21-day screening period, followed by a 26-week double-blind treatment period.
The product didn’t achieve the primary endpoint comparing reduction in hemoglobin A1c from baseline to 26 weeks, or the secondary endpoint of mean change in fasting plasma glucose at 26 weeks. There were no serious adverse events.
Oramed Pharmaceuticals specializes in developing oral delivery formulations of drugs currently delivered via injection. The company has offices in the United States and Israel.
Oramed CEO Nadav Kidron commented in the statement, “Today’s outcome is very disappointing, given the positive results from prior trials. Once full data from the studies are available, we expect to share relevant learnings and future plans. We thank all the patients, families, and health care professionals who participated in the trial.”
Insulin manufacturer Novo Nordisk had also been developing an oral insulin product. Successful phase 2a results were presented at the American Diabetes Association’s 2017 Scientific Sessions and full phase 2 feasibility results were published in Lancet Diabetes & Endocrinology in 2019.
However, Novo Nordisk, which manufactures the oral glucagon-like peptide-1 receptor agonist semaglutide (Rybelsus), subsequently discontinued development of their oral insulin product. According to a statement, “Initial results raised questions about truly addressing patients’ unmet needs with insulin therapy. Therefore, we discontinued this work to focus on projects that could in fact improve cardiometabolic outcomes for people living with diabetes.”
A version of this article first appeared on Medscape.com.
Latest steps toward reducing U.S. insulin cost begin in 2023
As of Jan. 1, 2023, the new provision tucked into the Inflation Reduction Act, signed into law by President Biden in August 2022, means that beneficiaries who take insulin via pen or syringe, covered under Medicare part D (prescription drugs), fall under the $35/month co-pay cap.
On July 1, 2023, the same out-of-pocket limit will also apply to those who take insulin via pump, which falls under Medicare part B (durable medical equipment).
The bill originally included the co-pay cap for people with private insurance as well, but that was stripped out as part of the reconciliation process and didn’t garner the necessary 60 Senate votes to keep it in prior to passage.
However, since 2019, 22 U.S. states have passed their own co-pay caps for people with state-regulated private insurance, ranging from $25 to $100 for a 30-day supply. A few states also cap the cost of diabetes devices as well.
Moreover, federal legislation could still address co-pay caps for people with private insurance, as well as include provisions to help those without insurance to afford insulin, Niels Knutson, director of government relations for the type 1 diabetes advocacy organization JDRF, told this news organization.
“There’s a whole menu of ideas on how to address the issue of insulin affordability. Most pathways to solving this on the federal level will require 60 votes in the Senate. There is universal recognition that this is a problem. The challenge becomes: is everybody on the same page for how to fix it,” Mr. Knutson said.
JDRF is supporting the bipartisan Improving Needed Safeguards for Users of Lifesaving Insulin Now (INSULIN) Act, introduced in June 2022 by U.S. Senators Jeanne Shaheen (D-NH) and Susan Collins (R-ME), who co-chair the Senate Diabetes Caucus. The bill includes a co-pay cap and also provisions to encourage insulin manufacturers to reduce their list prices.
“The bill is unique in that it adds a pathway to reduce the cost of insulin for everybody, regardless of whether they have insurance or not ... We see the Insulin Act as being the best path forward and the most viable path to have the biggest impact for the most people,” Mr. Knutson explained.
At the same time, JDRF is also supporting a nonprofit pharmaceutical company called Civica, which plans to bring biosimilar versions of the insulin analogs glargine, lispro, and aspart to the U.S. market by 2024 at a cost of no more than $30 for a vial and $50 for a box of prefilled pens. The state of California is expected to partner with Civica as well.
“This is just another access point for insulin, especially for folks who are uninsured, that would make a big impact,” Mr. Knutson said.
Other entities that have announced intentions to bring lower-cost insulin to the United States market include the Korean firm Undbio and billionaire entrepreneur Mark Cuban, through his company Cost Plus Drugs.
“Insulin is such a clear and present crisis that we need to address,” Mr. Knutson said. “You’re seeing this problem being recognized and solutions from all different angles coming at it.”
A version of this article first appeared on Medscape.com.
As of Jan. 1, 2023, the new provision tucked into the Inflation Reduction Act, signed into law by President Biden in August 2022, means that beneficiaries who take insulin via pen or syringe, covered under Medicare part D (prescription drugs), fall under the $35/month co-pay cap.
On July 1, 2023, the same out-of-pocket limit will also apply to those who take insulin via pump, which falls under Medicare part B (durable medical equipment).
The bill originally included the co-pay cap for people with private insurance as well, but that was stripped out as part of the reconciliation process and didn’t garner the necessary 60 Senate votes to keep it in prior to passage.
However, since 2019, 22 U.S. states have passed their own co-pay caps for people with state-regulated private insurance, ranging from $25 to $100 for a 30-day supply. A few states also cap the cost of diabetes devices as well.
Moreover, federal legislation could still address co-pay caps for people with private insurance, as well as include provisions to help those without insurance to afford insulin, Niels Knutson, director of government relations for the type 1 diabetes advocacy organization JDRF, told this news organization.
“There’s a whole menu of ideas on how to address the issue of insulin affordability. Most pathways to solving this on the federal level will require 60 votes in the Senate. There is universal recognition that this is a problem. The challenge becomes: is everybody on the same page for how to fix it,” Mr. Knutson said.
JDRF is supporting the bipartisan Improving Needed Safeguards for Users of Lifesaving Insulin Now (INSULIN) Act, introduced in June 2022 by U.S. Senators Jeanne Shaheen (D-NH) and Susan Collins (R-ME), who co-chair the Senate Diabetes Caucus. The bill includes a co-pay cap and also provisions to encourage insulin manufacturers to reduce their list prices.
“The bill is unique in that it adds a pathway to reduce the cost of insulin for everybody, regardless of whether they have insurance or not ... We see the Insulin Act as being the best path forward and the most viable path to have the biggest impact for the most people,” Mr. Knutson explained.
At the same time, JDRF is also supporting a nonprofit pharmaceutical company called Civica, which plans to bring biosimilar versions of the insulin analogs glargine, lispro, and aspart to the U.S. market by 2024 at a cost of no more than $30 for a vial and $50 for a box of prefilled pens. The state of California is expected to partner with Civica as well.
“This is just another access point for insulin, especially for folks who are uninsured, that would make a big impact,” Mr. Knutson said.
Other entities that have announced intentions to bring lower-cost insulin to the United States market include the Korean firm Undbio and billionaire entrepreneur Mark Cuban, through his company Cost Plus Drugs.
“Insulin is such a clear and present crisis that we need to address,” Mr. Knutson said. “You’re seeing this problem being recognized and solutions from all different angles coming at it.”
A version of this article first appeared on Medscape.com.
As of Jan. 1, 2023, the new provision tucked into the Inflation Reduction Act, signed into law by President Biden in August 2022, means that beneficiaries who take insulin via pen or syringe, covered under Medicare part D (prescription drugs), fall under the $35/month co-pay cap.
On July 1, 2023, the same out-of-pocket limit will also apply to those who take insulin via pump, which falls under Medicare part B (durable medical equipment).
The bill originally included the co-pay cap for people with private insurance as well, but that was stripped out as part of the reconciliation process and didn’t garner the necessary 60 Senate votes to keep it in prior to passage.
However, since 2019, 22 U.S. states have passed their own co-pay caps for people with state-regulated private insurance, ranging from $25 to $100 for a 30-day supply. A few states also cap the cost of diabetes devices as well.
Moreover, federal legislation could still address co-pay caps for people with private insurance, as well as include provisions to help those without insurance to afford insulin, Niels Knutson, director of government relations for the type 1 diabetes advocacy organization JDRF, told this news organization.
“There’s a whole menu of ideas on how to address the issue of insulin affordability. Most pathways to solving this on the federal level will require 60 votes in the Senate. There is universal recognition that this is a problem. The challenge becomes: is everybody on the same page for how to fix it,” Mr. Knutson said.
JDRF is supporting the bipartisan Improving Needed Safeguards for Users of Lifesaving Insulin Now (INSULIN) Act, introduced in June 2022 by U.S. Senators Jeanne Shaheen (D-NH) and Susan Collins (R-ME), who co-chair the Senate Diabetes Caucus. The bill includes a co-pay cap and also provisions to encourage insulin manufacturers to reduce their list prices.
“The bill is unique in that it adds a pathway to reduce the cost of insulin for everybody, regardless of whether they have insurance or not ... We see the Insulin Act as being the best path forward and the most viable path to have the biggest impact for the most people,” Mr. Knutson explained.
At the same time, JDRF is also supporting a nonprofit pharmaceutical company called Civica, which plans to bring biosimilar versions of the insulin analogs glargine, lispro, and aspart to the U.S. market by 2024 at a cost of no more than $30 for a vial and $50 for a box of prefilled pens. The state of California is expected to partner with Civica as well.
“This is just another access point for insulin, especially for folks who are uninsured, that would make a big impact,” Mr. Knutson said.
Other entities that have announced intentions to bring lower-cost insulin to the United States market include the Korean firm Undbio and billionaire entrepreneur Mark Cuban, through his company Cost Plus Drugs.
“Insulin is such a clear and present crisis that we need to address,” Mr. Knutson said. “You’re seeing this problem being recognized and solutions from all different angles coming at it.”
A version of this article first appeared on Medscape.com.
Dubious diagnosis: Is there a better way to define ‘prediabetes’?
and subsequent complications, and therefore merit more intensive intervention.
“Prediabetes” is the term coined to refer to either “impaired fasting glucose (IFG)” or “impaired glucose tolerance (IGT),” both denoting levels of elevated glycemia that don’t meet the thresholds for diabetes. It’s a heterogeneous group overall, and despite its name, not everyone with prediabetes will progress to develop type 2 diabetes.
There have been major increases in prediabetes in the United States and globally over the past 2 decades, epidemiologist Elizabeth Selvin, PhD, said at the recent IDF World Diabetes Congress 2022.
She noted that the concept of “prediabetes” has been controversial, previously dubbed a “dubious diagnosis” and a “boon for Pharma” in a 2019 Science article.
Others have said it’s “not a medical condition” and that it’s “an artificial category with virtually zero clinical relevance” in a press statement issued for a 2014 BMJ article.
“I don’t agree with these statements entirely but I think they speak to the confusion and tremendous controversy around the concept of prediabetes ... I think instead of calling prediabetes a ‘dubious diagnosis’ we should think of it as an opportunity,” said Dr. Selvin, of Johns Hopkins University Bloomberg School of Public Health, Baltimore.
She proposes trying to home in on those with highest risk of developing type 2 diabetes, which she suggests could be achieved by using a combination of elevated fasting glucose and an elevated A1c, although she stresses that this isn’t in any official guidance.
With the appropriate definition, people who are truly at risk for progression to type 2 diabetes can be identified so that lifestyle factors and cardiovascular risk can be addressed, and weight loss efforts implemented.
“Prevention of weight gain is ... important. That message often gets lost. Even if we can’t get people to lose weight, preventing [further] weight gain is important,” she noted.
Asked to comment, Sue Kirkman, MD, told this news organization, “The term prediabetes – or IFG or IGT or any of the ‘intermediate’ terms – is pragmatic in a way. It helps clinicians and patients understand that they are in a higher-risk category and might need intervention and likely need ongoing monitoring. But like many other risk factors [such as] blood pressure, [high] BMI, etc., the risk is not dichotomous but a continuum.
“People at the low end of the ‘intermediate’ range are not going to have much more risk compared to people who are ‘normal,’ while those at the high end of the range have very high risk,” said Dr. Kirkman, of the University of North Carolina, Chapel Hill, and a coauthor of the American Diabetes Association’s diabetes and prediabetes classifications.
“So we lose information if we just lump everyone into a single category. For individual patients, we definitely need better ways to estimate and communicate their potential risk.”
Currently five definitions for prediabetes: Home in on risk
The problem, Dr. Selvin explained, is that currently there are five official definitions for “prediabetes” using cutoffs for hemoglobin A1c, fasting glucose, or an oral glucose tolerance test.
Each one identifies different numbers of people with differing risk levels, ranging from a prevalence of 4.3% of the middle-aged adult population with the International Expert Committee’s definition of A1c 6.0%-6.4% to 43.5% with the American Diabetes Association’s 100-125 mg/dL fasting glucose.
“That’s an enormous difference. No wonder people are confused about who has prediabetes and what we should do about it,” Dr. Selvin said, adding that the concern about overdiagnosing “prediabetes” is even greater for older populations, in whom “it’s incredibly common to have mildly elevated glucose.”
Hence her proposal of what she sees as an evidence-based, “really easy solution” that clinicians can use now to better identify which patients with “intermediate hyperglycemia” to be most concerned about: Use a combination of fasting glucose above 100 mg/dL and an A1c greater than 5.7%.
“If you have both fasting glucose and hemoglobin A1c, you can use them together ... This is not codified in any guidelines. You won’t see this mentioned anywhere. The guidelines are silent on what to do when some people have an elevated fasting glucose but not an elevated A1c ... but I think a simple message is that if people have both an elevated fasting glucose and an elevated A1c, that’s a very high-risk group,” she said.
On the other hand, Dr. Kirkman pointed out, “most discrepancies are near the margins, as in one test is slightly elevated and one isn’t, so those people probably are at low risk.
“It may be that both being elevated means higher risk because they have more hyperglycemia ... so it seems reasonable, but only if it changes what you tell people.”
For example, Dr. Kirkman said, “I’d tell someone with A1c of 5.8% and fasting glucose of 99 mg/dL the same thing I’d tell someone with that A1c and a glucose of 104 mg/dL – that their risk is still pretty low – and I’d recommend healthy lifestyle and weight loss if overweight either way.”
However, she also said, “Certainly people with higher glucose or A1c are at much higher risk, and same for those with both.”
Tie “prediabetes” definition to risk, as cardiology scores do?
Dr. Selvin also believes that risk-based definitions of prediabetes are needed. Ideally, these would incorporate demographics and clinical factors such as age and body mass index. Other biomarkers could potentially be developed and validated for inclusion in the definition, such as C-reactive protein (CRP), lipids, or even genetic/proteomic information.
Moreover, she thinks that the definition should be tied to clinical decision-making, as is the pooled cohort equation in cardiology.
“I think we could do something very similar in prediabetes,” she suggested, adding that even simply incorporating age and BMI into the definition could help further stratify the risk level until other predictors are validated.
Dr. Kirkman said, “The concept of risk scores a la cardiology is interesting, although we’d have to make them simple and also validate them against some outcome.”
Regarding the age issue, Dr. Kirkman noted that although age wasn’t a predictor of progression to type 2 diabetes in the placebo arm of the landmark Diabetes Prevention Program (DPP) trial, “I do agree that it’s a problem that many older folks have the label of prediabetes because of a mildly elevated A1c and we know that most will never get diabetes.”
And, she noted, in the DPP people with prediabetes who had a BMI over 35 kg/m2 did have significantly higher progression rates than those with lower BMI, while women with a history of gestational diabetes mellitus are also known to be at particularly high risk.
Whom should we throw the kitchen sink at?
Some of this discussion, Dr. Kirkman said, “is really a philosophical one, especially when you consider that lifestyle intervention has benefits for almost everyone on many short- and long-term outcomes.”
“The question is probably whom we should ‘throw the kitchen sink at,’ who should get more scalable advice that might apply to everyone regardless of glycemic levels, and whether there’s some more intermediate group that needs more of a [National Diabetes Prevention Program] approach.”
Dr. Selvin’s group is now working on gathering data to inform development of a risk-based prediabetes definition. “We have a whole research effort in this area. I hope that with some really strong data on risk in prediabetes, that can help to solve the heterogeneity issue. I’m focused on bringing evidence to bear to change the guidelines.”
In the meantime, she told this news organization, “I think there are things we can do now to provide more guidance. I get a lot of feedback from people saying things like ‘my physician told me I have prediabetes but now I don’t’ or ‘I saw in my labs that my blood sugar is elevated but my doctor never said anything.’ That’s a communications issue where we can do a better job.”
The meeting was sponsored by the International Diabetes Federation.
Dr. Selvin is deputy editor of Diabetes Care and on the editorial board of Diabetologia. She receives funding from the NIH and the Foundation for the NIH, and royalties from UpToDate for sections related to screening, diagnosis, and laboratory testing for diabetes. Dr. Kirkman reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
and subsequent complications, and therefore merit more intensive intervention.
“Prediabetes” is the term coined to refer to either “impaired fasting glucose (IFG)” or “impaired glucose tolerance (IGT),” both denoting levels of elevated glycemia that don’t meet the thresholds for diabetes. It’s a heterogeneous group overall, and despite its name, not everyone with prediabetes will progress to develop type 2 diabetes.
There have been major increases in prediabetes in the United States and globally over the past 2 decades, epidemiologist Elizabeth Selvin, PhD, said at the recent IDF World Diabetes Congress 2022.
She noted that the concept of “prediabetes” has been controversial, previously dubbed a “dubious diagnosis” and a “boon for Pharma” in a 2019 Science article.
Others have said it’s “not a medical condition” and that it’s “an artificial category with virtually zero clinical relevance” in a press statement issued for a 2014 BMJ article.
“I don’t agree with these statements entirely but I think they speak to the confusion and tremendous controversy around the concept of prediabetes ... I think instead of calling prediabetes a ‘dubious diagnosis’ we should think of it as an opportunity,” said Dr. Selvin, of Johns Hopkins University Bloomberg School of Public Health, Baltimore.
She proposes trying to home in on those with highest risk of developing type 2 diabetes, which she suggests could be achieved by using a combination of elevated fasting glucose and an elevated A1c, although she stresses that this isn’t in any official guidance.
With the appropriate definition, people who are truly at risk for progression to type 2 diabetes can be identified so that lifestyle factors and cardiovascular risk can be addressed, and weight loss efforts implemented.
“Prevention of weight gain is ... important. That message often gets lost. Even if we can’t get people to lose weight, preventing [further] weight gain is important,” she noted.
Asked to comment, Sue Kirkman, MD, told this news organization, “The term prediabetes – or IFG or IGT or any of the ‘intermediate’ terms – is pragmatic in a way. It helps clinicians and patients understand that they are in a higher-risk category and might need intervention and likely need ongoing monitoring. But like many other risk factors [such as] blood pressure, [high] BMI, etc., the risk is not dichotomous but a continuum.
“People at the low end of the ‘intermediate’ range are not going to have much more risk compared to people who are ‘normal,’ while those at the high end of the range have very high risk,” said Dr. Kirkman, of the University of North Carolina, Chapel Hill, and a coauthor of the American Diabetes Association’s diabetes and prediabetes classifications.
“So we lose information if we just lump everyone into a single category. For individual patients, we definitely need better ways to estimate and communicate their potential risk.”
Currently five definitions for prediabetes: Home in on risk
The problem, Dr. Selvin explained, is that currently there are five official definitions for “prediabetes” using cutoffs for hemoglobin A1c, fasting glucose, or an oral glucose tolerance test.
Each one identifies different numbers of people with differing risk levels, ranging from a prevalence of 4.3% of the middle-aged adult population with the International Expert Committee’s definition of A1c 6.0%-6.4% to 43.5% with the American Diabetes Association’s 100-125 mg/dL fasting glucose.
“That’s an enormous difference. No wonder people are confused about who has prediabetes and what we should do about it,” Dr. Selvin said, adding that the concern about overdiagnosing “prediabetes” is even greater for older populations, in whom “it’s incredibly common to have mildly elevated glucose.”
Hence her proposal of what she sees as an evidence-based, “really easy solution” that clinicians can use now to better identify which patients with “intermediate hyperglycemia” to be most concerned about: Use a combination of fasting glucose above 100 mg/dL and an A1c greater than 5.7%.
“If you have both fasting glucose and hemoglobin A1c, you can use them together ... This is not codified in any guidelines. You won’t see this mentioned anywhere. The guidelines are silent on what to do when some people have an elevated fasting glucose but not an elevated A1c ... but I think a simple message is that if people have both an elevated fasting glucose and an elevated A1c, that’s a very high-risk group,” she said.
On the other hand, Dr. Kirkman pointed out, “most discrepancies are near the margins, as in one test is slightly elevated and one isn’t, so those people probably are at low risk.
“It may be that both being elevated means higher risk because they have more hyperglycemia ... so it seems reasonable, but only if it changes what you tell people.”
For example, Dr. Kirkman said, “I’d tell someone with A1c of 5.8% and fasting glucose of 99 mg/dL the same thing I’d tell someone with that A1c and a glucose of 104 mg/dL – that their risk is still pretty low – and I’d recommend healthy lifestyle and weight loss if overweight either way.”
However, she also said, “Certainly people with higher glucose or A1c are at much higher risk, and same for those with both.”
Tie “prediabetes” definition to risk, as cardiology scores do?
Dr. Selvin also believes that risk-based definitions of prediabetes are needed. Ideally, these would incorporate demographics and clinical factors such as age and body mass index. Other biomarkers could potentially be developed and validated for inclusion in the definition, such as C-reactive protein (CRP), lipids, or even genetic/proteomic information.
Moreover, she thinks that the definition should be tied to clinical decision-making, as is the pooled cohort equation in cardiology.
“I think we could do something very similar in prediabetes,” she suggested, adding that even simply incorporating age and BMI into the definition could help further stratify the risk level until other predictors are validated.
Dr. Kirkman said, “The concept of risk scores a la cardiology is interesting, although we’d have to make them simple and also validate them against some outcome.”
Regarding the age issue, Dr. Kirkman noted that although age wasn’t a predictor of progression to type 2 diabetes in the placebo arm of the landmark Diabetes Prevention Program (DPP) trial, “I do agree that it’s a problem that many older folks have the label of prediabetes because of a mildly elevated A1c and we know that most will never get diabetes.”
And, she noted, in the DPP people with prediabetes who had a BMI over 35 kg/m2 did have significantly higher progression rates than those with lower BMI, while women with a history of gestational diabetes mellitus are also known to be at particularly high risk.
Whom should we throw the kitchen sink at?
Some of this discussion, Dr. Kirkman said, “is really a philosophical one, especially when you consider that lifestyle intervention has benefits for almost everyone on many short- and long-term outcomes.”
“The question is probably whom we should ‘throw the kitchen sink at,’ who should get more scalable advice that might apply to everyone regardless of glycemic levels, and whether there’s some more intermediate group that needs more of a [National Diabetes Prevention Program] approach.”
Dr. Selvin’s group is now working on gathering data to inform development of a risk-based prediabetes definition. “We have a whole research effort in this area. I hope that with some really strong data on risk in prediabetes, that can help to solve the heterogeneity issue. I’m focused on bringing evidence to bear to change the guidelines.”
In the meantime, she told this news organization, “I think there are things we can do now to provide more guidance. I get a lot of feedback from people saying things like ‘my physician told me I have prediabetes but now I don’t’ or ‘I saw in my labs that my blood sugar is elevated but my doctor never said anything.’ That’s a communications issue where we can do a better job.”
The meeting was sponsored by the International Diabetes Federation.
Dr. Selvin is deputy editor of Diabetes Care and on the editorial board of Diabetologia. She receives funding from the NIH and the Foundation for the NIH, and royalties from UpToDate for sections related to screening, diagnosis, and laboratory testing for diabetes. Dr. Kirkman reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
and subsequent complications, and therefore merit more intensive intervention.
“Prediabetes” is the term coined to refer to either “impaired fasting glucose (IFG)” or “impaired glucose tolerance (IGT),” both denoting levels of elevated glycemia that don’t meet the thresholds for diabetes. It’s a heterogeneous group overall, and despite its name, not everyone with prediabetes will progress to develop type 2 diabetes.
There have been major increases in prediabetes in the United States and globally over the past 2 decades, epidemiologist Elizabeth Selvin, PhD, said at the recent IDF World Diabetes Congress 2022.
She noted that the concept of “prediabetes” has been controversial, previously dubbed a “dubious diagnosis” and a “boon for Pharma” in a 2019 Science article.
Others have said it’s “not a medical condition” and that it’s “an artificial category with virtually zero clinical relevance” in a press statement issued for a 2014 BMJ article.
“I don’t agree with these statements entirely but I think they speak to the confusion and tremendous controversy around the concept of prediabetes ... I think instead of calling prediabetes a ‘dubious diagnosis’ we should think of it as an opportunity,” said Dr. Selvin, of Johns Hopkins University Bloomberg School of Public Health, Baltimore.
She proposes trying to home in on those with highest risk of developing type 2 diabetes, which she suggests could be achieved by using a combination of elevated fasting glucose and an elevated A1c, although she stresses that this isn’t in any official guidance.
With the appropriate definition, people who are truly at risk for progression to type 2 diabetes can be identified so that lifestyle factors and cardiovascular risk can be addressed, and weight loss efforts implemented.
“Prevention of weight gain is ... important. That message often gets lost. Even if we can’t get people to lose weight, preventing [further] weight gain is important,” she noted.
Asked to comment, Sue Kirkman, MD, told this news organization, “The term prediabetes – or IFG or IGT or any of the ‘intermediate’ terms – is pragmatic in a way. It helps clinicians and patients understand that they are in a higher-risk category and might need intervention and likely need ongoing monitoring. But like many other risk factors [such as] blood pressure, [high] BMI, etc., the risk is not dichotomous but a continuum.
“People at the low end of the ‘intermediate’ range are not going to have much more risk compared to people who are ‘normal,’ while those at the high end of the range have very high risk,” said Dr. Kirkman, of the University of North Carolina, Chapel Hill, and a coauthor of the American Diabetes Association’s diabetes and prediabetes classifications.
“So we lose information if we just lump everyone into a single category. For individual patients, we definitely need better ways to estimate and communicate their potential risk.”
Currently five definitions for prediabetes: Home in on risk
The problem, Dr. Selvin explained, is that currently there are five official definitions for “prediabetes” using cutoffs for hemoglobin A1c, fasting glucose, or an oral glucose tolerance test.
Each one identifies different numbers of people with differing risk levels, ranging from a prevalence of 4.3% of the middle-aged adult population with the International Expert Committee’s definition of A1c 6.0%-6.4% to 43.5% with the American Diabetes Association’s 100-125 mg/dL fasting glucose.
“That’s an enormous difference. No wonder people are confused about who has prediabetes and what we should do about it,” Dr. Selvin said, adding that the concern about overdiagnosing “prediabetes” is even greater for older populations, in whom “it’s incredibly common to have mildly elevated glucose.”
Hence her proposal of what she sees as an evidence-based, “really easy solution” that clinicians can use now to better identify which patients with “intermediate hyperglycemia” to be most concerned about: Use a combination of fasting glucose above 100 mg/dL and an A1c greater than 5.7%.
“If you have both fasting glucose and hemoglobin A1c, you can use them together ... This is not codified in any guidelines. You won’t see this mentioned anywhere. The guidelines are silent on what to do when some people have an elevated fasting glucose but not an elevated A1c ... but I think a simple message is that if people have both an elevated fasting glucose and an elevated A1c, that’s a very high-risk group,” she said.
On the other hand, Dr. Kirkman pointed out, “most discrepancies are near the margins, as in one test is slightly elevated and one isn’t, so those people probably are at low risk.
“It may be that both being elevated means higher risk because they have more hyperglycemia ... so it seems reasonable, but only if it changes what you tell people.”
For example, Dr. Kirkman said, “I’d tell someone with A1c of 5.8% and fasting glucose of 99 mg/dL the same thing I’d tell someone with that A1c and a glucose of 104 mg/dL – that their risk is still pretty low – and I’d recommend healthy lifestyle and weight loss if overweight either way.”
However, she also said, “Certainly people with higher glucose or A1c are at much higher risk, and same for those with both.”
Tie “prediabetes” definition to risk, as cardiology scores do?
Dr. Selvin also believes that risk-based definitions of prediabetes are needed. Ideally, these would incorporate demographics and clinical factors such as age and body mass index. Other biomarkers could potentially be developed and validated for inclusion in the definition, such as C-reactive protein (CRP), lipids, or even genetic/proteomic information.
Moreover, she thinks that the definition should be tied to clinical decision-making, as is the pooled cohort equation in cardiology.
“I think we could do something very similar in prediabetes,” she suggested, adding that even simply incorporating age and BMI into the definition could help further stratify the risk level until other predictors are validated.
Dr. Kirkman said, “The concept of risk scores a la cardiology is interesting, although we’d have to make them simple and also validate them against some outcome.”
Regarding the age issue, Dr. Kirkman noted that although age wasn’t a predictor of progression to type 2 diabetes in the placebo arm of the landmark Diabetes Prevention Program (DPP) trial, “I do agree that it’s a problem that many older folks have the label of prediabetes because of a mildly elevated A1c and we know that most will never get diabetes.”
And, she noted, in the DPP people with prediabetes who had a BMI over 35 kg/m2 did have significantly higher progression rates than those with lower BMI, while women with a history of gestational diabetes mellitus are also known to be at particularly high risk.
Whom should we throw the kitchen sink at?
Some of this discussion, Dr. Kirkman said, “is really a philosophical one, especially when you consider that lifestyle intervention has benefits for almost everyone on many short- and long-term outcomes.”
“The question is probably whom we should ‘throw the kitchen sink at,’ who should get more scalable advice that might apply to everyone regardless of glycemic levels, and whether there’s some more intermediate group that needs more of a [National Diabetes Prevention Program] approach.”
Dr. Selvin’s group is now working on gathering data to inform development of a risk-based prediabetes definition. “We have a whole research effort in this area. I hope that with some really strong data on risk in prediabetes, that can help to solve the heterogeneity issue. I’m focused on bringing evidence to bear to change the guidelines.”
In the meantime, she told this news organization, “I think there are things we can do now to provide more guidance. I get a lot of feedback from people saying things like ‘my physician told me I have prediabetes but now I don’t’ or ‘I saw in my labs that my blood sugar is elevated but my doctor never said anything.’ That’s a communications issue where we can do a better job.”
The meeting was sponsored by the International Diabetes Federation.
Dr. Selvin is deputy editor of Diabetes Care and on the editorial board of Diabetologia. She receives funding from the NIH and the Foundation for the NIH, and royalties from UpToDate for sections related to screening, diagnosis, and laboratory testing for diabetes. Dr. Kirkman reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
AT IDF WORLD DIABETES CONGRESS 2022
ADA issues 2023 ‘Standards of Care’ for diabetes: Focus on tight BP, lipids
New more aggressive targets for blood pressure and lipids are among the changes to the annual American Diabetes Association (ADA) Standards of Care in Diabetes – 2023.
The document, long considered the gold standard for care of the more than 100 million Americans living with diabetes and prediabetes, was published as a supplement in Diabetes Care. The guidelines are also accessible to doctors via an app; last year’s standards were accessed more than 4 million times.
The standards now advise a blood pressure target for people with diabetes of less than 130/80 mm Hg, and low-density lipoprotein (LDL) cholesterol targets of below 70 mg/dL or no greater than 55 mg/dL, depending on the individual’s cardiovascular risk.
“In this year’s version of the ADA Standards of Care – the longstanding guidelines for diabetes management globally – you’ll see information that really speaks to how we can more aggressively treat diabetes and reduce complications in a variety of different ways,” ADA Chief Scientific and Medical Officer Robert A. Gabbay, MD, PhD, said in an interview.
Other changes for 2023 include a new emphasis on weight loss as a goal of therapy for type 2 diabetes; guidance for screening and assessing peripheral arterial disease in an effort to prevent amputations; use of finerenone in people with diabetes and chronic kidney disease; use of approved point-of-care A1c tests; and guidance on screening for food insecurity, along with an elevated role for community health workers.
“The management of type 2 diabetes is not just about glucose,” Dr. Gabbay emphasized, noting that the ADA Standards have increasingly focused on cardiorenal risk as well as weight management. “We need to think about all those things, not just one. We have better tools now that have been helpful in being able to move forward with this.”
New targets in cardiovascular disease and risk management
As it has been for the past 6 years, the section on cardiovascular disease and risk management is also endorsed by the American College of Cardiology.
The new definition of hypertension in people with diabetes is ≥ 130 mm Hg systolic or ≥ 80 mm Hg diastolic blood pressure, repeated on two measurements at different times. Among individuals with established cardiovascular disease, hypertension can be diagnosed with one measurement of ≥ 180/110 mm Hg.
The goal of treatment is now less than 130/80 mm Hg if it can be reached safely.
In 2012, easing of the systolic target to 140 mm Hg by the ADA caused some controversy.
But, as Dr. Gabbay explained: “The evidence wasn’t there 10 years ago. We stuck to the evidence at that time, although there was a belief that lower was better. Over the past decade, a number of studies have made it quite clear that there is benefit to a lower target. That’s why we staked out the ground on this.”
The new Standards of Care also has new lipid targets. For people with diabetes aged 40-75 years at increased cardiovascular risk, including those with one or more atherosclerotic risk factors, high-intensity statin therapy is recommended to reduce LDL cholesterol by 50% or more from baseline and to a target of less than 70 mg/dL, in contrast to the previous target of 100 mg/dL.
To achieve that goal, the document advises to consider adding ezetimibe or a PCSK9 inhibitor to maximally tolerated statin therapy.
For people with diabetes aged 40-75 who have established cardiovascular disease, treatment with high-intensity statin therapy is recommended with the target of a 50% or greater reduction from baseline and an LDL cholesterol level of 55 mg/dL or lower, in contrast to the previous 70 mg/dL.
“That is a lower goal than previously recommended, and based on strong evidence in the literature,” Dr. Gabbay noted.
Here, a stronger recommendation is made for ezetimibe or a PCSK9 inhibitor added to maximal statins.
And for people with diabetes older than 75 years, those already on statins should continue taking them. For those who aren’t, it may be reasonable to initiate moderate-intensity statin therapy after discussion of the benefits and risks.
Another new recommendation based on recent trial data is use of a sodium–glucose cotransporter 2 (SGLT2) inhibitor in people with diabetes and heart failure with preserved, as well as reduced, ejection fraction.
Kidney disease guidance updated: SGLT2 inhibitors, finerenone
Another recommendation calls for the addition of finerenone for people with type 2 diabetes who have chronic kidney disease (CKD) with albuminuria and have been treated with the maximum tolerated doses of an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) to improve cardiovascular outcomes as well as reduce the risk of CKD progression.
The threshold for initiating an SGLT2 inhibitor for kidney protection has changed to an estimated glomerular filtration rate (eGFR) ≥ 20 mL/min/1.73 m2 and urinary albumin ≥ 200 mg/g creatinine (previously ≥ 25 mL/min/1.73 m2 and ≥ 300 mg/g, respectively). An SGLT2 inhibitor may also be beneficial in people with a urinary albumin of normal to ≥ 200 mg/g creatinine, but supporting data have not yet been published.
Referral to a nephrologist is advised for individuals with increasing urinary albumin levels or continued decreasing eGFR or eGFR < 30 mL/min/1.73 m2.
Weight loss, point-of-care testing, food insecurity assessment
Other changes for 2023 include fresh emphasis on supporting weight loss of up to 15% with the new twincretin tirzepatide (Mounjaro) – approved in the United States in May for type 2 diabetes – added as a glucose-lowering drug with weight loss potential.
A novel section was added with guidance for peripheral arterial disease screening.
And a new recommendation advises use of point-of-care A1c testing for diabetes screening and diagnosis using only tests approved by the Food and Drug Administration.
Also introduced for 2023 is guidance to use community health workers to support the management of diabetes and cardiovascular risk factors, particularly in underserved areas and health systems.
“Community health workers can be a link to help people navigate and engage with the health system for better outcomes,” said Dr. Gabbay.
He added that these professionals are among those who can also assist with screening for food insecurity, another new recommendation. “We talk about screening for food insecurity and tools to use. That shouldn’t be something only dietitians do.”
Dr. Gabbay said he’d like to see more clinicians partner with community health workers. “We’d like to see more of that ... They should be considered part of the health care team,” he said.
Dr. Gabbay has reported serving on advisory boards for Lark, Health Reveal, Sweetch, StartUp Health, Vida Health, and Onduo.
A version of this article first appeared on Medscape.com.
New more aggressive targets for blood pressure and lipids are among the changes to the annual American Diabetes Association (ADA) Standards of Care in Diabetes – 2023.
The document, long considered the gold standard for care of the more than 100 million Americans living with diabetes and prediabetes, was published as a supplement in Diabetes Care. The guidelines are also accessible to doctors via an app; last year’s standards were accessed more than 4 million times.
The standards now advise a blood pressure target for people with diabetes of less than 130/80 mm Hg, and low-density lipoprotein (LDL) cholesterol targets of below 70 mg/dL or no greater than 55 mg/dL, depending on the individual’s cardiovascular risk.
“In this year’s version of the ADA Standards of Care – the longstanding guidelines for diabetes management globally – you’ll see information that really speaks to how we can more aggressively treat diabetes and reduce complications in a variety of different ways,” ADA Chief Scientific and Medical Officer Robert A. Gabbay, MD, PhD, said in an interview.
Other changes for 2023 include a new emphasis on weight loss as a goal of therapy for type 2 diabetes; guidance for screening and assessing peripheral arterial disease in an effort to prevent amputations; use of finerenone in people with diabetes and chronic kidney disease; use of approved point-of-care A1c tests; and guidance on screening for food insecurity, along with an elevated role for community health workers.
“The management of type 2 diabetes is not just about glucose,” Dr. Gabbay emphasized, noting that the ADA Standards have increasingly focused on cardiorenal risk as well as weight management. “We need to think about all those things, not just one. We have better tools now that have been helpful in being able to move forward with this.”
New targets in cardiovascular disease and risk management
As it has been for the past 6 years, the section on cardiovascular disease and risk management is also endorsed by the American College of Cardiology.
The new definition of hypertension in people with diabetes is ≥ 130 mm Hg systolic or ≥ 80 mm Hg diastolic blood pressure, repeated on two measurements at different times. Among individuals with established cardiovascular disease, hypertension can be diagnosed with one measurement of ≥ 180/110 mm Hg.
The goal of treatment is now less than 130/80 mm Hg if it can be reached safely.
In 2012, easing of the systolic target to 140 mm Hg by the ADA caused some controversy.
But, as Dr. Gabbay explained: “The evidence wasn’t there 10 years ago. We stuck to the evidence at that time, although there was a belief that lower was better. Over the past decade, a number of studies have made it quite clear that there is benefit to a lower target. That’s why we staked out the ground on this.”
The new Standards of Care also has new lipid targets. For people with diabetes aged 40-75 years at increased cardiovascular risk, including those with one or more atherosclerotic risk factors, high-intensity statin therapy is recommended to reduce LDL cholesterol by 50% or more from baseline and to a target of less than 70 mg/dL, in contrast to the previous target of 100 mg/dL.
To achieve that goal, the document advises to consider adding ezetimibe or a PCSK9 inhibitor to maximally tolerated statin therapy.
For people with diabetes aged 40-75 who have established cardiovascular disease, treatment with high-intensity statin therapy is recommended with the target of a 50% or greater reduction from baseline and an LDL cholesterol level of 55 mg/dL or lower, in contrast to the previous 70 mg/dL.
“That is a lower goal than previously recommended, and based on strong evidence in the literature,” Dr. Gabbay noted.
Here, a stronger recommendation is made for ezetimibe or a PCSK9 inhibitor added to maximal statins.
And for people with diabetes older than 75 years, those already on statins should continue taking them. For those who aren’t, it may be reasonable to initiate moderate-intensity statin therapy after discussion of the benefits and risks.
Another new recommendation based on recent trial data is use of a sodium–glucose cotransporter 2 (SGLT2) inhibitor in people with diabetes and heart failure with preserved, as well as reduced, ejection fraction.
Kidney disease guidance updated: SGLT2 inhibitors, finerenone
Another recommendation calls for the addition of finerenone for people with type 2 diabetes who have chronic kidney disease (CKD) with albuminuria and have been treated with the maximum tolerated doses of an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) to improve cardiovascular outcomes as well as reduce the risk of CKD progression.
The threshold for initiating an SGLT2 inhibitor for kidney protection has changed to an estimated glomerular filtration rate (eGFR) ≥ 20 mL/min/1.73 m2 and urinary albumin ≥ 200 mg/g creatinine (previously ≥ 25 mL/min/1.73 m2 and ≥ 300 mg/g, respectively). An SGLT2 inhibitor may also be beneficial in people with a urinary albumin of normal to ≥ 200 mg/g creatinine, but supporting data have not yet been published.
Referral to a nephrologist is advised for individuals with increasing urinary albumin levels or continued decreasing eGFR or eGFR < 30 mL/min/1.73 m2.
Weight loss, point-of-care testing, food insecurity assessment
Other changes for 2023 include fresh emphasis on supporting weight loss of up to 15% with the new twincretin tirzepatide (Mounjaro) – approved in the United States in May for type 2 diabetes – added as a glucose-lowering drug with weight loss potential.
A novel section was added with guidance for peripheral arterial disease screening.
And a new recommendation advises use of point-of-care A1c testing for diabetes screening and diagnosis using only tests approved by the Food and Drug Administration.
Also introduced for 2023 is guidance to use community health workers to support the management of diabetes and cardiovascular risk factors, particularly in underserved areas and health systems.
“Community health workers can be a link to help people navigate and engage with the health system for better outcomes,” said Dr. Gabbay.
He added that these professionals are among those who can also assist with screening for food insecurity, another new recommendation. “We talk about screening for food insecurity and tools to use. That shouldn’t be something only dietitians do.”
Dr. Gabbay said he’d like to see more clinicians partner with community health workers. “We’d like to see more of that ... They should be considered part of the health care team,” he said.
Dr. Gabbay has reported serving on advisory boards for Lark, Health Reveal, Sweetch, StartUp Health, Vida Health, and Onduo.
A version of this article first appeared on Medscape.com.
New more aggressive targets for blood pressure and lipids are among the changes to the annual American Diabetes Association (ADA) Standards of Care in Diabetes – 2023.
The document, long considered the gold standard for care of the more than 100 million Americans living with diabetes and prediabetes, was published as a supplement in Diabetes Care. The guidelines are also accessible to doctors via an app; last year’s standards were accessed more than 4 million times.
The standards now advise a blood pressure target for people with diabetes of less than 130/80 mm Hg, and low-density lipoprotein (LDL) cholesterol targets of below 70 mg/dL or no greater than 55 mg/dL, depending on the individual’s cardiovascular risk.
“In this year’s version of the ADA Standards of Care – the longstanding guidelines for diabetes management globally – you’ll see information that really speaks to how we can more aggressively treat diabetes and reduce complications in a variety of different ways,” ADA Chief Scientific and Medical Officer Robert A. Gabbay, MD, PhD, said in an interview.
Other changes for 2023 include a new emphasis on weight loss as a goal of therapy for type 2 diabetes; guidance for screening and assessing peripheral arterial disease in an effort to prevent amputations; use of finerenone in people with diabetes and chronic kidney disease; use of approved point-of-care A1c tests; and guidance on screening for food insecurity, along with an elevated role for community health workers.
“The management of type 2 diabetes is not just about glucose,” Dr. Gabbay emphasized, noting that the ADA Standards have increasingly focused on cardiorenal risk as well as weight management. “We need to think about all those things, not just one. We have better tools now that have been helpful in being able to move forward with this.”
New targets in cardiovascular disease and risk management
As it has been for the past 6 years, the section on cardiovascular disease and risk management is also endorsed by the American College of Cardiology.
The new definition of hypertension in people with diabetes is ≥ 130 mm Hg systolic or ≥ 80 mm Hg diastolic blood pressure, repeated on two measurements at different times. Among individuals with established cardiovascular disease, hypertension can be diagnosed with one measurement of ≥ 180/110 mm Hg.
The goal of treatment is now less than 130/80 mm Hg if it can be reached safely.
In 2012, easing of the systolic target to 140 mm Hg by the ADA caused some controversy.
But, as Dr. Gabbay explained: “The evidence wasn’t there 10 years ago. We stuck to the evidence at that time, although there was a belief that lower was better. Over the past decade, a number of studies have made it quite clear that there is benefit to a lower target. That’s why we staked out the ground on this.”
The new Standards of Care also has new lipid targets. For people with diabetes aged 40-75 years at increased cardiovascular risk, including those with one or more atherosclerotic risk factors, high-intensity statin therapy is recommended to reduce LDL cholesterol by 50% or more from baseline and to a target of less than 70 mg/dL, in contrast to the previous target of 100 mg/dL.
To achieve that goal, the document advises to consider adding ezetimibe or a PCSK9 inhibitor to maximally tolerated statin therapy.
For people with diabetes aged 40-75 who have established cardiovascular disease, treatment with high-intensity statin therapy is recommended with the target of a 50% or greater reduction from baseline and an LDL cholesterol level of 55 mg/dL or lower, in contrast to the previous 70 mg/dL.
“That is a lower goal than previously recommended, and based on strong evidence in the literature,” Dr. Gabbay noted.
Here, a stronger recommendation is made for ezetimibe or a PCSK9 inhibitor added to maximal statins.
And for people with diabetes older than 75 years, those already on statins should continue taking them. For those who aren’t, it may be reasonable to initiate moderate-intensity statin therapy after discussion of the benefits and risks.
Another new recommendation based on recent trial data is use of a sodium–glucose cotransporter 2 (SGLT2) inhibitor in people with diabetes and heart failure with preserved, as well as reduced, ejection fraction.
Kidney disease guidance updated: SGLT2 inhibitors, finerenone
Another recommendation calls for the addition of finerenone for people with type 2 diabetes who have chronic kidney disease (CKD) with albuminuria and have been treated with the maximum tolerated doses of an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) to improve cardiovascular outcomes as well as reduce the risk of CKD progression.
The threshold for initiating an SGLT2 inhibitor for kidney protection has changed to an estimated glomerular filtration rate (eGFR) ≥ 20 mL/min/1.73 m2 and urinary albumin ≥ 200 mg/g creatinine (previously ≥ 25 mL/min/1.73 m2 and ≥ 300 mg/g, respectively). An SGLT2 inhibitor may also be beneficial in people with a urinary albumin of normal to ≥ 200 mg/g creatinine, but supporting data have not yet been published.
Referral to a nephrologist is advised for individuals with increasing urinary albumin levels or continued decreasing eGFR or eGFR < 30 mL/min/1.73 m2.
Weight loss, point-of-care testing, food insecurity assessment
Other changes for 2023 include fresh emphasis on supporting weight loss of up to 15% with the new twincretin tirzepatide (Mounjaro) – approved in the United States in May for type 2 diabetes – added as a glucose-lowering drug with weight loss potential.
A novel section was added with guidance for peripheral arterial disease screening.
And a new recommendation advises use of point-of-care A1c testing for diabetes screening and diagnosis using only tests approved by the Food and Drug Administration.
Also introduced for 2023 is guidance to use community health workers to support the management of diabetes and cardiovascular risk factors, particularly in underserved areas and health systems.
“Community health workers can be a link to help people navigate and engage with the health system for better outcomes,” said Dr. Gabbay.
He added that these professionals are among those who can also assist with screening for food insecurity, another new recommendation. “We talk about screening for food insecurity and tools to use. That shouldn’t be something only dietitians do.”
Dr. Gabbay said he’d like to see more clinicians partner with community health workers. “We’d like to see more of that ... They should be considered part of the health care team,” he said.
Dr. Gabbay has reported serving on advisory boards for Lark, Health Reveal, Sweetch, StartUp Health, Vida Health, and Onduo.
A version of this article first appeared on Medscape.com.
FDA okays Dexcom G7 continuous glucose monitoring system
The U.S. Food and Drug Administration has cleared the Dexcom G7 continuous glucose monitoring (CGM) system for people with all types of diabetes aged 2 years and older and for use during pregnancy.
The G7 has several improvements over the current G6 model, including a 60% smaller size, a 30-minute warm-up period (compared with 2 hours), an all-in-one sensor and transmitter (as opposed to the two separate devices), a mean absolute relative difference (compared with a standard, an assessment of accuracy) of 8.2% (compared with 12.8%), a 12-hour grace period (in contrast to the G6’s hard shutoff), and a redesigned mobile app.
It is indicated for wear on the back of the upper arm for people aged 2 years and older or the upper buttocks for ages 2-17 years old.
As an “integrated” CGM, the G7 has the capacity to work as part of automated insulin delivery systems, but that will require further FDA action. “Dexcom is working closely with its insulin pump partners to integrate Dexcom G7 into current and future automated insulin delivery systems as quickly as possible,” the company said in a statement.
Like the G6, it requires no fingersticks, scanning, or calibration. It provides real-time glucose readings every 5 minutes to a compatible device, including Apple Watch and other digital health apps, and allows for remote monitoring of data by as many as 10 followers.
Dexcom expects to initiate a U.S. launch of Dexcom G7 in early 2023. To facilitate immediate access to G7 for as many users as possible, the company will have accessible cash pay options in place as the company transitions coverage with availability for G7, the statement says.
The Dexcom G7 was granted a CE Mark (Conformité Européenne) in March 2022, which means it is approved for use in people with diabetes aged 2 years and older, including pregnant women, in Europe.
A version of this article first appeared on Medscape.com.
The U.S. Food and Drug Administration has cleared the Dexcom G7 continuous glucose monitoring (CGM) system for people with all types of diabetes aged 2 years and older and for use during pregnancy.
The G7 has several improvements over the current G6 model, including a 60% smaller size, a 30-minute warm-up period (compared with 2 hours), an all-in-one sensor and transmitter (as opposed to the two separate devices), a mean absolute relative difference (compared with a standard, an assessment of accuracy) of 8.2% (compared with 12.8%), a 12-hour grace period (in contrast to the G6’s hard shutoff), and a redesigned mobile app.
It is indicated for wear on the back of the upper arm for people aged 2 years and older or the upper buttocks for ages 2-17 years old.
As an “integrated” CGM, the G7 has the capacity to work as part of automated insulin delivery systems, but that will require further FDA action. “Dexcom is working closely with its insulin pump partners to integrate Dexcom G7 into current and future automated insulin delivery systems as quickly as possible,” the company said in a statement.
Like the G6, it requires no fingersticks, scanning, or calibration. It provides real-time glucose readings every 5 minutes to a compatible device, including Apple Watch and other digital health apps, and allows for remote monitoring of data by as many as 10 followers.
Dexcom expects to initiate a U.S. launch of Dexcom G7 in early 2023. To facilitate immediate access to G7 for as many users as possible, the company will have accessible cash pay options in place as the company transitions coverage with availability for G7, the statement says.
The Dexcom G7 was granted a CE Mark (Conformité Européenne) in March 2022, which means it is approved for use in people with diabetes aged 2 years and older, including pregnant women, in Europe.
A version of this article first appeared on Medscape.com.
The U.S. Food and Drug Administration has cleared the Dexcom G7 continuous glucose monitoring (CGM) system for people with all types of diabetes aged 2 years and older and for use during pregnancy.
The G7 has several improvements over the current G6 model, including a 60% smaller size, a 30-minute warm-up period (compared with 2 hours), an all-in-one sensor and transmitter (as opposed to the two separate devices), a mean absolute relative difference (compared with a standard, an assessment of accuracy) of 8.2% (compared with 12.8%), a 12-hour grace period (in contrast to the G6’s hard shutoff), and a redesigned mobile app.
It is indicated for wear on the back of the upper arm for people aged 2 years and older or the upper buttocks for ages 2-17 years old.
As an “integrated” CGM, the G7 has the capacity to work as part of automated insulin delivery systems, but that will require further FDA action. “Dexcom is working closely with its insulin pump partners to integrate Dexcom G7 into current and future automated insulin delivery systems as quickly as possible,” the company said in a statement.
Like the G6, it requires no fingersticks, scanning, or calibration. It provides real-time glucose readings every 5 minutes to a compatible device, including Apple Watch and other digital health apps, and allows for remote monitoring of data by as many as 10 followers.
Dexcom expects to initiate a U.S. launch of Dexcom G7 in early 2023. To facilitate immediate access to G7 for as many users as possible, the company will have accessible cash pay options in place as the company transitions coverage with availability for G7, the statement says.
The Dexcom G7 was granted a CE Mark (Conformité Européenne) in March 2022, which means it is approved for use in people with diabetes aged 2 years and older, including pregnant women, in Europe.
A version of this article first appeared on Medscape.com.
With type 1 diabetes delay possible, focus now on screening
The recent approval of teplizumab-mzwv (Tzield, Provention Bio) for the delay of type 1 diabetes by the Food and Drug Administration is expected to advance efforts to increase screening to cost effectively identify those at risk for the condition who would be eligible to receive the new treatment.
The anti-CD3 monoclonal antibody was approved Nov. 17 as the first disease-modifying therapy for impeding progression of type 1 diabetes. In a clinical trial, teplizumab delayed the onset of clinical (stage 3) type 1 diabetes by approximately 2 years, and longer in some cases.
It is administered by intravenous infusion once daily for 14 consecutive days and is expected to cost in the region of $200,000 for the course of treatment.
The specific indication is “to delay the onset of stage 3 type 1 diabetes in adults and pediatric patients 8 years and older who currently have stage 2 type 1 diabetes.” In stage 2 type 1 diabetes, the individual has two or more islet autoantibodies and abnormal glycemia but is as yet asymptomatic. It is associated with a nearly 100% lifetime risk of progression to clinical (stage 3) type 1 diabetes and a 75% risk of developing the condition within 5 years.
Currently, most people who are screened for type 1 diabetes autoantibodies are first-degree relatives of those with the condition through TrialNet, other local programs, or more recently, a $55 test offered by the research and advocacy organization JDRF.
But because 85%-90% of people who develop type 1 diabetes don’t have first-degree relatives with the condition, broader population screening will be necessary to identify eligible candidates for teplizumab.
During an investor call on Nov. 18, Provention Bio chief commercial officer Jason Hoitt said that among the company’s “strategic initiatives” were “advancing awareness and screening for autoantibodies in at-risk individuals, and ultimately, routine screening during pediatric well visits for the general population,” as well as “[health care provider] belief in teplizumab and desire to prescribe it for their patients.”
Without broad population-based screening, first-degree relatives of people with type 1 diabetes are likely to be the first to be screened and those with stage 2 identified for receipt of teplizumab. Today, that population is estimated at about 30,000 in the United States, Mr. Hoitt said, adding, “with this approval we hope that more stage 2 patients can be readily identified so the course of the disease can be changed.”
During the call, Mr. Hoitt also announced that the wholesale acquisition cost of Tzield would be $13,850 per vial, which translates to $193,900 per 14-vial continuous regimen, anticipated to be a sufficient dose for most patients. The company also launched a program called COMPASS to help patients navigate insurance reimbursement, as well as provide some with financial assistance.
Cost aside, JDRF CEO Aaron Kowalski, PhD, said in an interview that clinicians shouldn’t doubt the value of delaying type 1 diabetes onset, even if not completely preventing it. “This is the first drug ever to treat the underlying disease. There is this undercurrent that insulin is enough. Why would you undertake an additional risk of an immunotherapy? Type 1 is hard to live with. I think sometimes the clinical community doesn’t appreciate that insulin is not enough. It’s very difficult, and opening this door is important. ... We believe very strongly that the delay of onset of type 1 diabetes is clinically meaningful. We hear that from every family we’ve talked to. Clinicians should appreciate this and not discount it.”
How would screening happen?
While the path to universal screening for type 1 diabetes risk isn’t yet clear, quite a bit of thought and research has gone into it even before teplizumab and other immune-modulating agents showed promise in forestalling the condition.
Data from a universal screening program of schoolchildren implemented in Bavaria, Germany, and a screening program in Denver, suggest that even without such an intervention, identifying people at high risk for developing type 1 diabetes could be cost effective by allowing for education of the individual and family members about the signs of type 1 diabetes, thereby reducing the likelihood that the person would progress to developing diabetic ketoacidosis (DKA) prior to diagnosis.
Another study that used data from the United States and Western Europe, found that screening children for type 1 diabetes–associated islet autoantibodies at ages 2 and 6 years would identify most of those who go on to develop the disease by midadolescence.
However, using a genetic risk score at birth to identify those who would go on to autoantibody testing is potentially a more cost-effective approach, William A. Hagopian, MD, PhD, director of diabetes programs, Pacific Northwest Research Institute, Seattle, said in an interview.
The score – based on human leukocyte antigen haplotypes and their interactions as well as non-HLA genes – can stratify nearly 80% of childhood type 1 diabetes within the top 10% of all newborns. Thus, only the top 10% would then go on to receive the more expensive autoantibody testing.
“I’ve been working with U.K. colleagues for the past 3-4 years to develop a strategy using genetic risk scores followed by autoantibody screening. I feel strongly that that’s the cost-effective way to go. It’s relatively inexpensive, scalable, and can be applied commercially in newborn screening labs. To be successful an approach must be cost effective. Payors are willing to pay for newborn screening, but not so much on testing 100% of kids for antibodies,” Dr. Hagopian said.
He is now working with Washington State newborn screening labs to demonstrate feasibility of the approach using dried blood samples from actual neonatal screening after obtaining informed consent from the mothers in postpartum wards in several hospitals. Those found to be at high risk using the genetic risk score are contacted for follow-up with autoantibody screening. The program will continue for another year and a half. “I think it actually has a chance of being accepted into their regular program,” he said.
And then, he hopes, other states will follow, and eventually, the strategy will be added to the Recommended Uniform Screening Panel for universal newborn screening programs, as recommended by the Department of Health & Human Services.
“New newborn screenings for additional diseases are implemented regularly,” Dr. Hagopian said. “Most are far less common than type 1 diabetes. So even if our approach is less than 100% sensitive, this condition is a lot more common than the many inborn errors of metabolism, so we’re still going to be identifying a lot of cases. ... This is my hope for how universal type 1 diabetes screening will unfold. I see a way this may work quite well.”
A two-pronged approach to screening could work best
Meanwhile, JDRF, which supported the teplizumab research as well as others working in the space, is focusing on both genetic and autoantibody screening, Dr. Kowalski said.
“JDRF is working on both pathways – testing kids at birth for genetic predisposition and also antibody screening. We have huge programs focused on general population antibody screening.”
Dr. Kowalski said that, while the two-pronged approach certainly is worth exploring – and JDRF is doing that – he also thinks that universal autoantibody screening could be cost effective if done efficiently, such as with less expensive assays than the one used in TrialNet.
“We have programs where you do the genetic screening and keep an eye on people. We also have programs, like the one we’re funding in Germany, that are doing broad autoantibody screening of all kids. We’re hopeful that will be very cost effective if we move to cheaper assays.”
He noted that the proportion of children with new-onset type 1 diabetes who present in DKA rose from 40% pre–COVID-19 to 50% during the early days of the pandemic. On the other hand, “With screening you can get that to near zero, like they did in Bavaria. Here [in the United States], one ICU visit for DKA [costs] $100,000.”
While JDRF and others have been working on this for years, the new availability of teplizumab will be “multifold in helping things along. ... I think you’re going to see a lot of work on the cost-effectiveness of teplizumab. I think the case will be pretty straightforward that there’s huge upside to delaying the disease from a near-term and a long-term cost perspective. This is the first time we’ve had a drug out there with a price attached to it.”
But it may not happen quickly, Kowalski cautioned. “I feel there’s a ... series of events that has to happen to drive towards universal screening. Here in the U.S. it’s complicated because we have a very discrepant health care system with all these different payers, public and private.”
During the investor call, Mr. Hoitt said that Provention Bio is also exploring use of Tzield in younger patients and newly diagnosed patients, and the potential benefit of redosing or combining with other treatments.
Mr. Hoitt is an employee of Provention Bio. Dr. Kowalski is an employee of JDRF. Dr. Hagopian has reported receiving study funding from Janssen.
A version of this article first appeared on Medscape.com.
The recent approval of teplizumab-mzwv (Tzield, Provention Bio) for the delay of type 1 diabetes by the Food and Drug Administration is expected to advance efforts to increase screening to cost effectively identify those at risk for the condition who would be eligible to receive the new treatment.
The anti-CD3 monoclonal antibody was approved Nov. 17 as the first disease-modifying therapy for impeding progression of type 1 diabetes. In a clinical trial, teplizumab delayed the onset of clinical (stage 3) type 1 diabetes by approximately 2 years, and longer in some cases.
It is administered by intravenous infusion once daily for 14 consecutive days and is expected to cost in the region of $200,000 for the course of treatment.
The specific indication is “to delay the onset of stage 3 type 1 diabetes in adults and pediatric patients 8 years and older who currently have stage 2 type 1 diabetes.” In stage 2 type 1 diabetes, the individual has two or more islet autoantibodies and abnormal glycemia but is as yet asymptomatic. It is associated with a nearly 100% lifetime risk of progression to clinical (stage 3) type 1 diabetes and a 75% risk of developing the condition within 5 years.
Currently, most people who are screened for type 1 diabetes autoantibodies are first-degree relatives of those with the condition through TrialNet, other local programs, or more recently, a $55 test offered by the research and advocacy organization JDRF.
But because 85%-90% of people who develop type 1 diabetes don’t have first-degree relatives with the condition, broader population screening will be necessary to identify eligible candidates for teplizumab.
During an investor call on Nov. 18, Provention Bio chief commercial officer Jason Hoitt said that among the company’s “strategic initiatives” were “advancing awareness and screening for autoantibodies in at-risk individuals, and ultimately, routine screening during pediatric well visits for the general population,” as well as “[health care provider] belief in teplizumab and desire to prescribe it for their patients.”
Without broad population-based screening, first-degree relatives of people with type 1 diabetes are likely to be the first to be screened and those with stage 2 identified for receipt of teplizumab. Today, that population is estimated at about 30,000 in the United States, Mr. Hoitt said, adding, “with this approval we hope that more stage 2 patients can be readily identified so the course of the disease can be changed.”
During the call, Mr. Hoitt also announced that the wholesale acquisition cost of Tzield would be $13,850 per vial, which translates to $193,900 per 14-vial continuous regimen, anticipated to be a sufficient dose for most patients. The company also launched a program called COMPASS to help patients navigate insurance reimbursement, as well as provide some with financial assistance.
Cost aside, JDRF CEO Aaron Kowalski, PhD, said in an interview that clinicians shouldn’t doubt the value of delaying type 1 diabetes onset, even if not completely preventing it. “This is the first drug ever to treat the underlying disease. There is this undercurrent that insulin is enough. Why would you undertake an additional risk of an immunotherapy? Type 1 is hard to live with. I think sometimes the clinical community doesn’t appreciate that insulin is not enough. It’s very difficult, and opening this door is important. ... We believe very strongly that the delay of onset of type 1 diabetes is clinically meaningful. We hear that from every family we’ve talked to. Clinicians should appreciate this and not discount it.”
How would screening happen?
While the path to universal screening for type 1 diabetes risk isn’t yet clear, quite a bit of thought and research has gone into it even before teplizumab and other immune-modulating agents showed promise in forestalling the condition.
Data from a universal screening program of schoolchildren implemented in Bavaria, Germany, and a screening program in Denver, suggest that even without such an intervention, identifying people at high risk for developing type 1 diabetes could be cost effective by allowing for education of the individual and family members about the signs of type 1 diabetes, thereby reducing the likelihood that the person would progress to developing diabetic ketoacidosis (DKA) prior to diagnosis.
Another study that used data from the United States and Western Europe, found that screening children for type 1 diabetes–associated islet autoantibodies at ages 2 and 6 years would identify most of those who go on to develop the disease by midadolescence.
However, using a genetic risk score at birth to identify those who would go on to autoantibody testing is potentially a more cost-effective approach, William A. Hagopian, MD, PhD, director of diabetes programs, Pacific Northwest Research Institute, Seattle, said in an interview.
The score – based on human leukocyte antigen haplotypes and their interactions as well as non-HLA genes – can stratify nearly 80% of childhood type 1 diabetes within the top 10% of all newborns. Thus, only the top 10% would then go on to receive the more expensive autoantibody testing.
“I’ve been working with U.K. colleagues for the past 3-4 years to develop a strategy using genetic risk scores followed by autoantibody screening. I feel strongly that that’s the cost-effective way to go. It’s relatively inexpensive, scalable, and can be applied commercially in newborn screening labs. To be successful an approach must be cost effective. Payors are willing to pay for newborn screening, but not so much on testing 100% of kids for antibodies,” Dr. Hagopian said.
He is now working with Washington State newborn screening labs to demonstrate feasibility of the approach using dried blood samples from actual neonatal screening after obtaining informed consent from the mothers in postpartum wards in several hospitals. Those found to be at high risk using the genetic risk score are contacted for follow-up with autoantibody screening. The program will continue for another year and a half. “I think it actually has a chance of being accepted into their regular program,” he said.
And then, he hopes, other states will follow, and eventually, the strategy will be added to the Recommended Uniform Screening Panel for universal newborn screening programs, as recommended by the Department of Health & Human Services.
“New newborn screenings for additional diseases are implemented regularly,” Dr. Hagopian said. “Most are far less common than type 1 diabetes. So even if our approach is less than 100% sensitive, this condition is a lot more common than the many inborn errors of metabolism, so we’re still going to be identifying a lot of cases. ... This is my hope for how universal type 1 diabetes screening will unfold. I see a way this may work quite well.”
A two-pronged approach to screening could work best
Meanwhile, JDRF, which supported the teplizumab research as well as others working in the space, is focusing on both genetic and autoantibody screening, Dr. Kowalski said.
“JDRF is working on both pathways – testing kids at birth for genetic predisposition and also antibody screening. We have huge programs focused on general population antibody screening.”
Dr. Kowalski said that, while the two-pronged approach certainly is worth exploring – and JDRF is doing that – he also thinks that universal autoantibody screening could be cost effective if done efficiently, such as with less expensive assays than the one used in TrialNet.
“We have programs where you do the genetic screening and keep an eye on people. We also have programs, like the one we’re funding in Germany, that are doing broad autoantibody screening of all kids. We’re hopeful that will be very cost effective if we move to cheaper assays.”
He noted that the proportion of children with new-onset type 1 diabetes who present in DKA rose from 40% pre–COVID-19 to 50% during the early days of the pandemic. On the other hand, “With screening you can get that to near zero, like they did in Bavaria. Here [in the United States], one ICU visit for DKA [costs] $100,000.”
While JDRF and others have been working on this for years, the new availability of teplizumab will be “multifold in helping things along. ... I think you’re going to see a lot of work on the cost-effectiveness of teplizumab. I think the case will be pretty straightforward that there’s huge upside to delaying the disease from a near-term and a long-term cost perspective. This is the first time we’ve had a drug out there with a price attached to it.”
But it may not happen quickly, Kowalski cautioned. “I feel there’s a ... series of events that has to happen to drive towards universal screening. Here in the U.S. it’s complicated because we have a very discrepant health care system with all these different payers, public and private.”
During the investor call, Mr. Hoitt said that Provention Bio is also exploring use of Tzield in younger patients and newly diagnosed patients, and the potential benefit of redosing or combining with other treatments.
Mr. Hoitt is an employee of Provention Bio. Dr. Kowalski is an employee of JDRF. Dr. Hagopian has reported receiving study funding from Janssen.
A version of this article first appeared on Medscape.com.
The recent approval of teplizumab-mzwv (Tzield, Provention Bio) for the delay of type 1 diabetes by the Food and Drug Administration is expected to advance efforts to increase screening to cost effectively identify those at risk for the condition who would be eligible to receive the new treatment.
The anti-CD3 monoclonal antibody was approved Nov. 17 as the first disease-modifying therapy for impeding progression of type 1 diabetes. In a clinical trial, teplizumab delayed the onset of clinical (stage 3) type 1 diabetes by approximately 2 years, and longer in some cases.
It is administered by intravenous infusion once daily for 14 consecutive days and is expected to cost in the region of $200,000 for the course of treatment.
The specific indication is “to delay the onset of stage 3 type 1 diabetes in adults and pediatric patients 8 years and older who currently have stage 2 type 1 diabetes.” In stage 2 type 1 diabetes, the individual has two or more islet autoantibodies and abnormal glycemia but is as yet asymptomatic. It is associated with a nearly 100% lifetime risk of progression to clinical (stage 3) type 1 diabetes and a 75% risk of developing the condition within 5 years.
Currently, most people who are screened for type 1 diabetes autoantibodies are first-degree relatives of those with the condition through TrialNet, other local programs, or more recently, a $55 test offered by the research and advocacy organization JDRF.
But because 85%-90% of people who develop type 1 diabetes don’t have first-degree relatives with the condition, broader population screening will be necessary to identify eligible candidates for teplizumab.
During an investor call on Nov. 18, Provention Bio chief commercial officer Jason Hoitt said that among the company’s “strategic initiatives” were “advancing awareness and screening for autoantibodies in at-risk individuals, and ultimately, routine screening during pediatric well visits for the general population,” as well as “[health care provider] belief in teplizumab and desire to prescribe it for their patients.”
Without broad population-based screening, first-degree relatives of people with type 1 diabetes are likely to be the first to be screened and those with stage 2 identified for receipt of teplizumab. Today, that population is estimated at about 30,000 in the United States, Mr. Hoitt said, adding, “with this approval we hope that more stage 2 patients can be readily identified so the course of the disease can be changed.”
During the call, Mr. Hoitt also announced that the wholesale acquisition cost of Tzield would be $13,850 per vial, which translates to $193,900 per 14-vial continuous regimen, anticipated to be a sufficient dose for most patients. The company also launched a program called COMPASS to help patients navigate insurance reimbursement, as well as provide some with financial assistance.
Cost aside, JDRF CEO Aaron Kowalski, PhD, said in an interview that clinicians shouldn’t doubt the value of delaying type 1 diabetes onset, even if not completely preventing it. “This is the first drug ever to treat the underlying disease. There is this undercurrent that insulin is enough. Why would you undertake an additional risk of an immunotherapy? Type 1 is hard to live with. I think sometimes the clinical community doesn’t appreciate that insulin is not enough. It’s very difficult, and opening this door is important. ... We believe very strongly that the delay of onset of type 1 diabetes is clinically meaningful. We hear that from every family we’ve talked to. Clinicians should appreciate this and not discount it.”
How would screening happen?
While the path to universal screening for type 1 diabetes risk isn’t yet clear, quite a bit of thought and research has gone into it even before teplizumab and other immune-modulating agents showed promise in forestalling the condition.
Data from a universal screening program of schoolchildren implemented in Bavaria, Germany, and a screening program in Denver, suggest that even without such an intervention, identifying people at high risk for developing type 1 diabetes could be cost effective by allowing for education of the individual and family members about the signs of type 1 diabetes, thereby reducing the likelihood that the person would progress to developing diabetic ketoacidosis (DKA) prior to diagnosis.
Another study that used data from the United States and Western Europe, found that screening children for type 1 diabetes–associated islet autoantibodies at ages 2 and 6 years would identify most of those who go on to develop the disease by midadolescence.
However, using a genetic risk score at birth to identify those who would go on to autoantibody testing is potentially a more cost-effective approach, William A. Hagopian, MD, PhD, director of diabetes programs, Pacific Northwest Research Institute, Seattle, said in an interview.
The score – based on human leukocyte antigen haplotypes and their interactions as well as non-HLA genes – can stratify nearly 80% of childhood type 1 diabetes within the top 10% of all newborns. Thus, only the top 10% would then go on to receive the more expensive autoantibody testing.
“I’ve been working with U.K. colleagues for the past 3-4 years to develop a strategy using genetic risk scores followed by autoantibody screening. I feel strongly that that’s the cost-effective way to go. It’s relatively inexpensive, scalable, and can be applied commercially in newborn screening labs. To be successful an approach must be cost effective. Payors are willing to pay for newborn screening, but not so much on testing 100% of kids for antibodies,” Dr. Hagopian said.
He is now working with Washington State newborn screening labs to demonstrate feasibility of the approach using dried blood samples from actual neonatal screening after obtaining informed consent from the mothers in postpartum wards in several hospitals. Those found to be at high risk using the genetic risk score are contacted for follow-up with autoantibody screening. The program will continue for another year and a half. “I think it actually has a chance of being accepted into their regular program,” he said.
And then, he hopes, other states will follow, and eventually, the strategy will be added to the Recommended Uniform Screening Panel for universal newborn screening programs, as recommended by the Department of Health & Human Services.
“New newborn screenings for additional diseases are implemented regularly,” Dr. Hagopian said. “Most are far less common than type 1 diabetes. So even if our approach is less than 100% sensitive, this condition is a lot more common than the many inborn errors of metabolism, so we’re still going to be identifying a lot of cases. ... This is my hope for how universal type 1 diabetes screening will unfold. I see a way this may work quite well.”
A two-pronged approach to screening could work best
Meanwhile, JDRF, which supported the teplizumab research as well as others working in the space, is focusing on both genetic and autoantibody screening, Dr. Kowalski said.
“JDRF is working on both pathways – testing kids at birth for genetic predisposition and also antibody screening. We have huge programs focused on general population antibody screening.”
Dr. Kowalski said that, while the two-pronged approach certainly is worth exploring – and JDRF is doing that – he also thinks that universal autoantibody screening could be cost effective if done efficiently, such as with less expensive assays than the one used in TrialNet.
“We have programs where you do the genetic screening and keep an eye on people. We also have programs, like the one we’re funding in Germany, that are doing broad autoantibody screening of all kids. We’re hopeful that will be very cost effective if we move to cheaper assays.”
He noted that the proportion of children with new-onset type 1 diabetes who present in DKA rose from 40% pre–COVID-19 to 50% during the early days of the pandemic. On the other hand, “With screening you can get that to near zero, like they did in Bavaria. Here [in the United States], one ICU visit for DKA [costs] $100,000.”
While JDRF and others have been working on this for years, the new availability of teplizumab will be “multifold in helping things along. ... I think you’re going to see a lot of work on the cost-effectiveness of teplizumab. I think the case will be pretty straightforward that there’s huge upside to delaying the disease from a near-term and a long-term cost perspective. This is the first time we’ve had a drug out there with a price attached to it.”
But it may not happen quickly, Kowalski cautioned. “I feel there’s a ... series of events that has to happen to drive towards universal screening. Here in the U.S. it’s complicated because we have a very discrepant health care system with all these different payers, public and private.”
During the investor call, Mr. Hoitt said that Provention Bio is also exploring use of Tzield in younger patients and newly diagnosed patients, and the potential benefit of redosing or combining with other treatments.
Mr. Hoitt is an employee of Provention Bio. Dr. Kowalski is an employee of JDRF. Dr. Hagopian has reported receiving study funding from Janssen.
A version of this article first appeared on Medscape.com.
FDA approves first-ever agent to delay type 1 diabetes onset
“Today’s approval of a first-in-class therapy adds an important new treatment option for certain at-risk patients,” said John Sharretts, MD, director of the Division of Diabetes, Lipid Disorders, and Obesity in the FDA’s Center for Drug Evaluation and Research. “The drug’s potential to delay clinical diagnosis of type 1 diabetes may provide patients with months to years without the burdens of disease.”
The agent, which interferes with T-cell-mediated autoimmune destruction of pancreatic beta cells, is the first disease-modifying therapy for impeding progression of type 1 diabetes. It is administered by intravenous infusion once daily for 14 consecutive days.
The specific indication is “to delay the onset of stage 3 type 1 diabetes in adults and pediatric patients 8 years and older who currently have stage 2 type 1 diabetes.” In type 1 diabetes staging, adopted in 2015, stage 1 is defined as the presence of beta cell autoimmunity with two or more islet autoantibodies with normoglycemia, stage 2 is beta-cell autoimmunity with dysglycemia yet asymptomatic, and stage 3 is the onset of symptomatic type 1 diabetes.
Stage 2 type 1 diabetes is associated with a nearly 100% lifetime risk of progression to clinical (stage 3) type 1 diabetes and a 75% risk of developing the condition within 5 years.
The FDA had previously rejected teplizumab for this indication in July 2021, despite a prior endorsement from an advisory panel in May 2021.
Now, with the FDA approval, Provention Bio cofounder and CEO Ashleigh Palmer said in a statement, “This is a historic occasion for the T1D community and a paradigm shifting breakthrough ... It cannot be emphasized enough how precious a delay in the onset of stage 3 T1D can be from a patient and family perspective; more time to live without and, when necessary, prepare for the burdens, complications, and risks associated with stage 3 disease.”
T1D onset delayed by 2 years
In 2019, a pivotal phase 2, randomized, placebo-controlled trial involving 76 at-risk children and adults aged 8 years and older showed that a single 14-day treatment of daily intravenous infusions of teplizumab in 44 patients resulted in a significant median 2-year delay to onset of clinical type 1 diabetes compared with 32 who received placebo.
Those “game changer” data were presented at the American Diabetes Association (ADA) annual meeting in June 2019 and simultaneously published in the New England Journal of Medicine.
Three-year data were presented at the June 2020 ADA meeting and published in March 2021 in Science Translational Medicine, by Emily K. Sims, MD, department of pediatrics, Indiana University, Indianapolis, and colleagues.
At a median follow-up of 923 days, 50% of those randomly assigned to teplizumab remained diabetes free, compared with 22% of those who received placebo infusions (hazard ratio, 0.457; P = .01). The teplizumab group had a greater average C-peptide area under the curve compared with placebo, reflecting improved beta-cell function (1.96 vs. 1.68 pmol/mL; P = .006).
C-peptide levels declined over time in the placebo group but stabilized in those receiving teplizumab (P = .0015).
“The mid-range time from randomization to stage 3 type 1 diabetes diagnosis was 50 months for the patients who received Tzield and 25 months for those who received a placebo. This represents a statistically significant delay in the development of stage 3 type 1 diabetes,” according to the FDA statement.
The most common side effects of Tzield include lymphopenia (73% teplizumab vs. 6% placebo), rash (36% vs. 0%), leukopenia (221% vs. 0%), and headache (11% vs. 6%). Label warnings and precautions include monitoring for cytokine release syndrome, risk for serious infections, and avoidance of live, inactivated, and mRNA vaccines.
This approval is likely to accelerate discussion about universal autoantibody screening. Currently, most individuals identified as having preclinical type 1 diabetes are first-degree relatives of people with type 1 diabetes identified through the federally funded TrialNet program. In December 2020, the type 1 diabetes research and advocacy organization JDRF began offering a $55 home blood test to screen for the antibodies, and other screening programs have been launched in the United States and Europe.
Previous studies have examined cost-effectiveness of universal screening in children and the optimal ages that such screening should take place.
In October, Provention Bio announced a co-promotion agreement with Sanofi for the U.S. launch of Tzield for delay in onset of clinical T1D in at-risk individuals. Provention Bio offers financial assistance options (e.g., copay assistance) to eligible patients for out-of-pocket costs.
A version of this article first appeared on Medscape.com.
“Today’s approval of a first-in-class therapy adds an important new treatment option for certain at-risk patients,” said John Sharretts, MD, director of the Division of Diabetes, Lipid Disorders, and Obesity in the FDA’s Center for Drug Evaluation and Research. “The drug’s potential to delay clinical diagnosis of type 1 diabetes may provide patients with months to years without the burdens of disease.”
The agent, which interferes with T-cell-mediated autoimmune destruction of pancreatic beta cells, is the first disease-modifying therapy for impeding progression of type 1 diabetes. It is administered by intravenous infusion once daily for 14 consecutive days.
The specific indication is “to delay the onset of stage 3 type 1 diabetes in adults and pediatric patients 8 years and older who currently have stage 2 type 1 diabetes.” In type 1 diabetes staging, adopted in 2015, stage 1 is defined as the presence of beta cell autoimmunity with two or more islet autoantibodies with normoglycemia, stage 2 is beta-cell autoimmunity with dysglycemia yet asymptomatic, and stage 3 is the onset of symptomatic type 1 diabetes.
Stage 2 type 1 diabetes is associated with a nearly 100% lifetime risk of progression to clinical (stage 3) type 1 diabetes and a 75% risk of developing the condition within 5 years.
The FDA had previously rejected teplizumab for this indication in July 2021, despite a prior endorsement from an advisory panel in May 2021.
Now, with the FDA approval, Provention Bio cofounder and CEO Ashleigh Palmer said in a statement, “This is a historic occasion for the T1D community and a paradigm shifting breakthrough ... It cannot be emphasized enough how precious a delay in the onset of stage 3 T1D can be from a patient and family perspective; more time to live without and, when necessary, prepare for the burdens, complications, and risks associated with stage 3 disease.”
T1D onset delayed by 2 years
In 2019, a pivotal phase 2, randomized, placebo-controlled trial involving 76 at-risk children and adults aged 8 years and older showed that a single 14-day treatment of daily intravenous infusions of teplizumab in 44 patients resulted in a significant median 2-year delay to onset of clinical type 1 diabetes compared with 32 who received placebo.
Those “game changer” data were presented at the American Diabetes Association (ADA) annual meeting in June 2019 and simultaneously published in the New England Journal of Medicine.
Three-year data were presented at the June 2020 ADA meeting and published in March 2021 in Science Translational Medicine, by Emily K. Sims, MD, department of pediatrics, Indiana University, Indianapolis, and colleagues.
At a median follow-up of 923 days, 50% of those randomly assigned to teplizumab remained diabetes free, compared with 22% of those who received placebo infusions (hazard ratio, 0.457; P = .01). The teplizumab group had a greater average C-peptide area under the curve compared with placebo, reflecting improved beta-cell function (1.96 vs. 1.68 pmol/mL; P = .006).
C-peptide levels declined over time in the placebo group but stabilized in those receiving teplizumab (P = .0015).
“The mid-range time from randomization to stage 3 type 1 diabetes diagnosis was 50 months for the patients who received Tzield and 25 months for those who received a placebo. This represents a statistically significant delay in the development of stage 3 type 1 diabetes,” according to the FDA statement.
The most common side effects of Tzield include lymphopenia (73% teplizumab vs. 6% placebo), rash (36% vs. 0%), leukopenia (221% vs. 0%), and headache (11% vs. 6%). Label warnings and precautions include monitoring for cytokine release syndrome, risk for serious infections, and avoidance of live, inactivated, and mRNA vaccines.
This approval is likely to accelerate discussion about universal autoantibody screening. Currently, most individuals identified as having preclinical type 1 diabetes are first-degree relatives of people with type 1 diabetes identified through the federally funded TrialNet program. In December 2020, the type 1 diabetes research and advocacy organization JDRF began offering a $55 home blood test to screen for the antibodies, and other screening programs have been launched in the United States and Europe.
Previous studies have examined cost-effectiveness of universal screening in children and the optimal ages that such screening should take place.
In October, Provention Bio announced a co-promotion agreement with Sanofi for the U.S. launch of Tzield for delay in onset of clinical T1D in at-risk individuals. Provention Bio offers financial assistance options (e.g., copay assistance) to eligible patients for out-of-pocket costs.
A version of this article first appeared on Medscape.com.
“Today’s approval of a first-in-class therapy adds an important new treatment option for certain at-risk patients,” said John Sharretts, MD, director of the Division of Diabetes, Lipid Disorders, and Obesity in the FDA’s Center for Drug Evaluation and Research. “The drug’s potential to delay clinical diagnosis of type 1 diabetes may provide patients with months to years without the burdens of disease.”
The agent, which interferes with T-cell-mediated autoimmune destruction of pancreatic beta cells, is the first disease-modifying therapy for impeding progression of type 1 diabetes. It is administered by intravenous infusion once daily for 14 consecutive days.
The specific indication is “to delay the onset of stage 3 type 1 diabetes in adults and pediatric patients 8 years and older who currently have stage 2 type 1 diabetes.” In type 1 diabetes staging, adopted in 2015, stage 1 is defined as the presence of beta cell autoimmunity with two or more islet autoantibodies with normoglycemia, stage 2 is beta-cell autoimmunity with dysglycemia yet asymptomatic, and stage 3 is the onset of symptomatic type 1 diabetes.
Stage 2 type 1 diabetes is associated with a nearly 100% lifetime risk of progression to clinical (stage 3) type 1 diabetes and a 75% risk of developing the condition within 5 years.
The FDA had previously rejected teplizumab for this indication in July 2021, despite a prior endorsement from an advisory panel in May 2021.
Now, with the FDA approval, Provention Bio cofounder and CEO Ashleigh Palmer said in a statement, “This is a historic occasion for the T1D community and a paradigm shifting breakthrough ... It cannot be emphasized enough how precious a delay in the onset of stage 3 T1D can be from a patient and family perspective; more time to live without and, when necessary, prepare for the burdens, complications, and risks associated with stage 3 disease.”
T1D onset delayed by 2 years
In 2019, a pivotal phase 2, randomized, placebo-controlled trial involving 76 at-risk children and adults aged 8 years and older showed that a single 14-day treatment of daily intravenous infusions of teplizumab in 44 patients resulted in a significant median 2-year delay to onset of clinical type 1 diabetes compared with 32 who received placebo.
Those “game changer” data were presented at the American Diabetes Association (ADA) annual meeting in June 2019 and simultaneously published in the New England Journal of Medicine.
Three-year data were presented at the June 2020 ADA meeting and published in March 2021 in Science Translational Medicine, by Emily K. Sims, MD, department of pediatrics, Indiana University, Indianapolis, and colleagues.
At a median follow-up of 923 days, 50% of those randomly assigned to teplizumab remained diabetes free, compared with 22% of those who received placebo infusions (hazard ratio, 0.457; P = .01). The teplizumab group had a greater average C-peptide area under the curve compared with placebo, reflecting improved beta-cell function (1.96 vs. 1.68 pmol/mL; P = .006).
C-peptide levels declined over time in the placebo group but stabilized in those receiving teplizumab (P = .0015).
“The mid-range time from randomization to stage 3 type 1 diabetes diagnosis was 50 months for the patients who received Tzield and 25 months for those who received a placebo. This represents a statistically significant delay in the development of stage 3 type 1 diabetes,” according to the FDA statement.
The most common side effects of Tzield include lymphopenia (73% teplizumab vs. 6% placebo), rash (36% vs. 0%), leukopenia (221% vs. 0%), and headache (11% vs. 6%). Label warnings and precautions include monitoring for cytokine release syndrome, risk for serious infections, and avoidance of live, inactivated, and mRNA vaccines.
This approval is likely to accelerate discussion about universal autoantibody screening. Currently, most individuals identified as having preclinical type 1 diabetes are first-degree relatives of people with type 1 diabetes identified through the federally funded TrialNet program. In December 2020, the type 1 diabetes research and advocacy organization JDRF began offering a $55 home blood test to screen for the antibodies, and other screening programs have been launched in the United States and Europe.
Previous studies have examined cost-effectiveness of universal screening in children and the optimal ages that such screening should take place.
In October, Provention Bio announced a co-promotion agreement with Sanofi for the U.S. launch of Tzield for delay in onset of clinical T1D in at-risk individuals. Provention Bio offers financial assistance options (e.g., copay assistance) to eligible patients for out-of-pocket costs.
A version of this article first appeared on Medscape.com.