Type 2 Diabetes ICYMI

Key clinical point: In patients with type 2 diabetes (T2D), initiating or switching to insulin degludec/ aspart (IDegAsp) from other antidiabetic treatments was associated with improved glycemic control, lower basal insulin dose requirement in insulin-experienced patients, and lower rates of hypoglycemia.

Major finding: Patients with T2D initiating or switching to IDegAsp had a significant reduction in glycated hemoglobin (estimated difference [Δ] −1.4%; P < .0001), basal insulin dose requirements in insulin-experienced participants (Δ −2.3 units; P  =  .0004), and rates of hypoglycemia (P < .001).

Study details: Findings are from a real-world, prospective study including 1102 patients with T2D who initiated or switched to IDegAsp from other antidiabetic treatments.

Disclosures: This study was funded by Novo Nordisk. Some authors declared being employees and shareholders of Novo Nordisk. Some authors declared receiving speaker or consulting honoraria, research contracts, and teaching or research sponsorships; being consultants; or serving as advisory board or speaker panel members for various sources, including Novo Nordisk.

Source: Fulcher GR et al. Initiating or switching to insulin degludec/insulin aspart in adults with type 2 diabetes: A real-world, prospective, non-interventional study across six countries. Adv Ther. 2022 (Jun 25). Doi: 10.1007/s12325-022-02212-3

Key clinical point: In patients with type 2 diabetes (T2D), initiating or switching to insulin degludec/ aspart (IDegAsp) from other antidiabetic treatments was associated with improved glycemic control, lower basal insulin dose requirement in insulin-experienced patients, and lower rates of hypoglycemia.

Major finding: Patients with T2D initiating or switching to IDegAsp had a significant reduction in glycated hemoglobin (estimated difference [Δ] −1.4%; P < .0001), basal insulin dose requirements in insulin-experienced participants (Δ −2.3 units; P  =  .0004), and rates of hypoglycemia (P < .001).

Study details: Findings are from a real-world, prospective study including 1102 patients with T2D who initiated or switched to IDegAsp from other antidiabetic treatments.

Disclosures: This study was funded by Novo Nordisk. Some authors declared being employees and shareholders of Novo Nordisk. Some authors declared receiving speaker or consulting honoraria, research contracts, and teaching or research sponsorships; being consultants; or serving as advisory board or speaker panel members for various sources, including Novo Nordisk.

Source: Fulcher GR et al. Initiating or switching to insulin degludec/insulin aspart in adults with type 2 diabetes: A real-world, prospective, non-interventional study across six countries. Adv Ther. 2022 (Jun 25). Doi: 10.1007/s12325-022-02212-3

Key clinical point: In patients with type 2 diabetes (T2D), initiating or switching to insulin degludec/ aspart (IDegAsp) from other antidiabetic treatments was associated with improved glycemic control, lower basal insulin dose requirement in insulin-experienced patients, and lower rates of hypoglycemia.

Major finding: Patients with T2D initiating or switching to IDegAsp had a significant reduction in glycated hemoglobin (estimated difference [Δ] −1.4%; P < .0001), basal insulin dose requirements in insulin-experienced participants (Δ −2.3 units; P  =  .0004), and rates of hypoglycemia (P < .001).

Study details: Findings are from a real-world, prospective study including 1102 patients with T2D who initiated or switched to IDegAsp from other antidiabetic treatments.

Disclosures: This study was funded by Novo Nordisk. Some authors declared being employees and shareholders of Novo Nordisk. Some authors declared receiving speaker or consulting honoraria, research contracts, and teaching or research sponsorships; being consultants; or serving as advisory board or speaker panel members for various sources, including Novo Nordisk.

Source: Fulcher GR et al. Initiating or switching to insulin degludec/insulin aspart in adults with type 2 diabetes: A real-world, prospective, non-interventional study across six countries. Adv Ther. 2022 (Jun 25). Doi: 10.1007/s12325-022-02212-3

Key clinical point: Sodium-glucose cotransporter 2 inhibitor (SGLT2i) use in patients with type 2 diabetes mellitus (T2D) is associated with a significantly lower risk for all-cause and cause-specific death compared with dipeptidyl peptidase 4 inhibitor (DPP4i) use.

Major finding: Patients receiving SGLT2i vs DPP4i had a lower risk for all-cause death (adjusted hazard ratio [aHR] 0.66; P < .001), cardiovascular death (aHR 0.68; P < .001), cancer death (aHR 0.73; P  =  .003), and noncancer and nonvascular death (aHR 0.62; P < .001).

Study details: This nationwide retrospective cohort study matched patients with T2D who initiated SGLT2i (n = 53,264) with those who initiated DPP4i (n = 53,264) using propensity score matching.

Disclosures: This study was partly supported by grants from China Medical University Hospital, Ditmanson Medical Foundation Chiayi Christian Hospital, and the Ministry of Science and Technology of Taiwan. No competing interests were declared.

Source: Chung M-C et al. Efficacy and safety of DBPR108 (prusogliptin) as an add-on to metformin therapy in patients with type 2 diabetes mellitus: A 24-week, multi-center, randomized, double-blind, placebo-controlled, superiority, phase III clinical trial. Sci Rep. 2022;12:10147 (Jun 16). Doi: 10.1038/s41598-022-13760-7

Key clinical point: Sodium-glucose cotransporter 2 inhibitor (SGLT2i) use in patients with type 2 diabetes mellitus (T2D) is associated with a significantly lower risk for all-cause and cause-specific death compared with dipeptidyl peptidase 4 inhibitor (DPP4i) use.

Major finding: Patients receiving SGLT2i vs DPP4i had a lower risk for all-cause death (adjusted hazard ratio [aHR] 0.66; P < .001), cardiovascular death (aHR 0.68; P < .001), cancer death (aHR 0.73; P  =  .003), and noncancer and nonvascular death (aHR 0.62; P < .001).

Study details: This nationwide retrospective cohort study matched patients with T2D who initiated SGLT2i (n = 53,264) with those who initiated DPP4i (n = 53,264) using propensity score matching.

Disclosures: This study was partly supported by grants from China Medical University Hospital, Ditmanson Medical Foundation Chiayi Christian Hospital, and the Ministry of Science and Technology of Taiwan. No competing interests were declared.

Source: Chung M-C et al. Efficacy and safety of DBPR108 (prusogliptin) as an add-on to metformin therapy in patients with type 2 diabetes mellitus: A 24-week, multi-center, randomized, double-blind, placebo-controlled, superiority, phase III clinical trial. Sci Rep. 2022;12:10147 (Jun 16). Doi: 10.1038/s41598-022-13760-7

Key clinical point: Sodium-glucose cotransporter 2 inhibitor (SGLT2i) use in patients with type 2 diabetes mellitus (T2D) is associated with a significantly lower risk for all-cause and cause-specific death compared with dipeptidyl peptidase 4 inhibitor (DPP4i) use.

Major finding: Patients receiving SGLT2i vs DPP4i had a lower risk for all-cause death (adjusted hazard ratio [aHR] 0.66; P < .001), cardiovascular death (aHR 0.68; P < .001), cancer death (aHR 0.73; P  =  .003), and noncancer and nonvascular death (aHR 0.62; P < .001).

Study details: This nationwide retrospective cohort study matched patients with T2D who initiated SGLT2i (n = 53,264) with those who initiated DPP4i (n = 53,264) using propensity score matching.

Disclosures: This study was partly supported by grants from China Medical University Hospital, Ditmanson Medical Foundation Chiayi Christian Hospital, and the Ministry of Science and Technology of Taiwan. No competing interests were declared.

Source: Chung M-C et al. Efficacy and safety of DBPR108 (prusogliptin) as an add-on to metformin therapy in patients with type 2 diabetes mellitus: A 24-week, multi-center, randomized, double-blind, placebo-controlled, superiority, phase III clinical trial. Sci Rep. 2022;12:10147 (Jun 16). Doi: 10.1038/s41598-022-13760-7

Key clinical point: Prusogliptin as an add-on therapy to metformin was superior to metformin monotherapy in improving glycemic control and was safe and well tolerated in patients with type 2 diabetes mellitus (T2D) inadequately controlled with metformin.

Major finding: At week 24, prusogliptin + metformin vs metformin + placebo led to significantly higher reductions in glycated hemoglobin (least squares mean change [LSM] −0.70% vs −0.07%; P < .001), fasting plasma glucose (LSM −0.63 vs 0.07 mmol/L; P  =  .025), and 2-hour postprandial plasma glucose (LSM −2.43 vs −0.70 mmol/L; P < .001) levels, with the incidence of adverse events being similar between the treatment groups.

Study details: Findings are from a 24-week, superiority, phase 3 trial including 206 patients with T2D with blood glucose levels inadequately controlled on metformin who were randomly assigned to receive prusogliptin + metformin (n = 138) or placebo + metformin (n = 68).

Disclosures: This study was funded by the CSPC Zhongqi Pharmaceutical Technology Co., Ltd. Some authors are employees of CSPC Zhongqi Pharmaceutical Technology.

Source: Xu J et al. Efficacy and safety of DBPR108 (prusogliptin) as an add-on to metformin therapy in patients with type 2 diabetes mellitus: A 24-week, multi-center, randomized, double-blind, placebo-controlled, superiority, phase III clinical trial. Diabetes Obes Metab. 2022 (Jul 6). Doi: 10.1111/dom.14810

Key clinical point: Prusogliptin as an add-on therapy to metformin was superior to metformin monotherapy in improving glycemic control and was safe and well tolerated in patients with type 2 diabetes mellitus (T2D) inadequately controlled with metformin.

Major finding: At week 24, prusogliptin + metformin vs metformin + placebo led to significantly higher reductions in glycated hemoglobin (least squares mean change [LSM] −0.70% vs −0.07%; P < .001), fasting plasma glucose (LSM −0.63 vs 0.07 mmol/L; P  =  .025), and 2-hour postprandial plasma glucose (LSM −2.43 vs −0.70 mmol/L; P < .001) levels, with the incidence of adverse events being similar between the treatment groups.

Study details: Findings are from a 24-week, superiority, phase 3 trial including 206 patients with T2D with blood glucose levels inadequately controlled on metformin who were randomly assigned to receive prusogliptin + metformin (n = 138) or placebo + metformin (n = 68).

Disclosures: This study was funded by the CSPC Zhongqi Pharmaceutical Technology Co., Ltd. Some authors are employees of CSPC Zhongqi Pharmaceutical Technology.

Source: Xu J et al. Efficacy and safety of DBPR108 (prusogliptin) as an add-on to metformin therapy in patients with type 2 diabetes mellitus: A 24-week, multi-center, randomized, double-blind, placebo-controlled, superiority, phase III clinical trial. Diabetes Obes Metab. 2022 (Jul 6). Doi: 10.1111/dom.14810

Key clinical point: Prusogliptin as an add-on therapy to metformin was superior to metformin monotherapy in improving glycemic control and was safe and well tolerated in patients with type 2 diabetes mellitus (T2D) inadequately controlled with metformin.

Major finding: At week 24, prusogliptin + metformin vs metformin + placebo led to significantly higher reductions in glycated hemoglobin (least squares mean change [LSM] −0.70% vs −0.07%; P < .001), fasting plasma glucose (LSM −0.63 vs 0.07 mmol/L; P  =  .025), and 2-hour postprandial plasma glucose (LSM −2.43 vs −0.70 mmol/L; P < .001) levels, with the incidence of adverse events being similar between the treatment groups.

Study details: Findings are from a 24-week, superiority, phase 3 trial including 206 patients with T2D with blood glucose levels inadequately controlled on metformin who were randomly assigned to receive prusogliptin + metformin (n = 138) or placebo + metformin (n = 68).

Disclosures: This study was funded by the CSPC Zhongqi Pharmaceutical Technology Co., Ltd. Some authors are employees of CSPC Zhongqi Pharmaceutical Technology.

Source: Xu J et al. Efficacy and safety of DBPR108 (prusogliptin) as an add-on to metformin therapy in patients with type 2 diabetes mellitus: A 24-week, multi-center, randomized, double-blind, placebo-controlled, superiority, phase III clinical trial. Diabetes Obes Metab. 2022 (Jul 6). Doi: 10.1111/dom.14810

Key clinical point: Initiation of semaglutide in patients with type 2 diabetes mellitus (T2D) on high daily doses of insulin at baseline led to a significant improvement in glycemic control, body weight, and reduction in total daily dose (TDD) of insulin.

Major finding: From baseline to 6 months, the TDD of insulin (183 ± 98 to 143 ± 99 units, respectively), glycated hemoglobin level (8.9% ± 1.3% to 7.6% ± 1.5%, respectively), and body weight (123.9 ± 23.5 to 118.9 ± 22.9 kg, respectively; all P < .001) reduced significantly in patients on high daily doses of insulin who received semaglutide.

Study details: Findings are from a retrospective analysis including 72 patients with T2D on high TDD of insulin (≥100 units) who were prescribed semaglutide.

Disclosures: This study received no specific funding. The authors declared no conflicts of interest.

Source: Meyer J et al. The effects of adding semaglutide to high daily dose insulin regimens in patients with type 2 diabetes. Ann Pharmacother. 2022 (Jul 1). Doi: 10.1177/10600280221107381

Key clinical point: Initiation of semaglutide in patients with type 2 diabetes mellitus (T2D) on high daily doses of insulin at baseline led to a significant improvement in glycemic control, body weight, and reduction in total daily dose (TDD) of insulin.

Major finding: From baseline to 6 months, the TDD of insulin (183 ± 98 to 143 ± 99 units, respectively), glycated hemoglobin level (8.9% ± 1.3% to 7.6% ± 1.5%, respectively), and body weight (123.9 ± 23.5 to 118.9 ± 22.9 kg, respectively; all P < .001) reduced significantly in patients on high daily doses of insulin who received semaglutide.

Study details: Findings are from a retrospective analysis including 72 patients with T2D on high TDD of insulin (≥100 units) who were prescribed semaglutide.

Disclosures: This study received no specific funding. The authors declared no conflicts of interest.

Source: Meyer J et al. The effects of adding semaglutide to high daily dose insulin regimens in patients with type 2 diabetes. Ann Pharmacother. 2022 (Jul 1). Doi: 10.1177/10600280221107381

Key clinical point: Initiation of semaglutide in patients with type 2 diabetes mellitus (T2D) on high daily doses of insulin at baseline led to a significant improvement in glycemic control, body weight, and reduction in total daily dose (TDD) of insulin.

Major finding: From baseline to 6 months, the TDD of insulin (183 ± 98 to 143 ± 99 units, respectively), glycated hemoglobin level (8.9% ± 1.3% to 7.6% ± 1.5%, respectively), and body weight (123.9 ± 23.5 to 118.9 ± 22.9 kg, respectively; all P < .001) reduced significantly in patients on high daily doses of insulin who received semaglutide.

Study details: Findings are from a retrospective analysis including 72 patients with T2D on high TDD of insulin (≥100 units) who were prescribed semaglutide.

Disclosures: This study received no specific funding. The authors declared no conflicts of interest.

Source: Meyer J et al. The effects of adding semaglutide to high daily dose insulin regimens in patients with type 2 diabetes. Ann Pharmacother. 2022 (Jul 1). Doi: 10.1177/10600280221107381

Key clinical point: Dipeptidyl peptidase-4 (DPP4) inhibitors significantly increased the risk for the composite of gallbladder or biliary diseases and cholecystitis but not for cholelithiasis and biliary diseases in patients with type 2 diabetes (T2D), especially those with a longer treatment duration.

Major finding: Compared with placebo or non-incretin drugs, DPP4 inhibitors were associated with a significantly higher risk for composite of gallbladder or biliary diseases (odds ratio [OR] 1.22; 95% CI 1.04-1.43) and cholecystitis (OR 1.43; 95% CI 1.14-1.79), but not for cholelithiasis (OR 1.08; 95% CI 0.83-1.39) and biliary diseases (OR 1.00; 95% CI 0.68-1.47), and the association remained significant with the long-term (≥26 weeks) use of DPP4 inhibitors.

Study details: The data come from a systematic review and pairwise meta-analysis of 82 randomized trials including 104,833 patients with T2D.

Disclosures: This study was partially supported by Beijing Natural Science Foundation, National Natural Science Foundation of China, and others. The authors declared receiving support from the funding institutions.

Source: He L et al. Dipeptidyl peptidase-4 inhibitors and gallbladder or biliary disease in type 2 diabetes: systematic review and pairwise and network meta-analysis of randomised controlled trials BMJ. 2022;377:e068882 (Jun 28). Doi: 10.1136/bmj-2021-068882

Key clinical point: Dipeptidyl peptidase-4 (DPP4) inhibitors significantly increased the risk for the composite of gallbladder or biliary diseases and cholecystitis but not for cholelithiasis and biliary diseases in patients with type 2 diabetes (T2D), especially those with a longer treatment duration.

Major finding: Compared with placebo or non-incretin drugs, DPP4 inhibitors were associated with a significantly higher risk for composite of gallbladder or biliary diseases (odds ratio [OR] 1.22; 95% CI 1.04-1.43) and cholecystitis (OR 1.43; 95% CI 1.14-1.79), but not for cholelithiasis (OR 1.08; 95% CI 0.83-1.39) and biliary diseases (OR 1.00; 95% CI 0.68-1.47), and the association remained significant with the long-term (≥26 weeks) use of DPP4 inhibitors.

Study details: The data come from a systematic review and pairwise meta-analysis of 82 randomized trials including 104,833 patients with T2D.

Disclosures: This study was partially supported by Beijing Natural Science Foundation, National Natural Science Foundation of China, and others. The authors declared receiving support from the funding institutions.

Source: He L et al. Dipeptidyl peptidase-4 inhibitors and gallbladder or biliary disease in type 2 diabetes: systematic review and pairwise and network meta-analysis of randomised controlled trials BMJ. 2022;377:e068882 (Jun 28). Doi: 10.1136/bmj-2021-068882

Key clinical point: Dipeptidyl peptidase-4 (DPP4) inhibitors significantly increased the risk for the composite of gallbladder or biliary diseases and cholecystitis but not for cholelithiasis and biliary diseases in patients with type 2 diabetes (T2D), especially those with a longer treatment duration.

Major finding: Compared with placebo or non-incretin drugs, DPP4 inhibitors were associated with a significantly higher risk for composite of gallbladder or biliary diseases (odds ratio [OR] 1.22; 95% CI 1.04-1.43) and cholecystitis (OR 1.43; 95% CI 1.14-1.79), but not for cholelithiasis (OR 1.08; 95% CI 0.83-1.39) and biliary diseases (OR 1.00; 95% CI 0.68-1.47), and the association remained significant with the long-term (≥26 weeks) use of DPP4 inhibitors.

Study details: The data come from a systematic review and pairwise meta-analysis of 82 randomized trials including 104,833 patients with T2D.

Disclosures: This study was partially supported by Beijing Natural Science Foundation, National Natural Science Foundation of China, and others. The authors declared receiving support from the funding institutions.

Source: He L et al. Dipeptidyl peptidase-4 inhibitors and gallbladder or biliary disease in type 2 diabetes: systematic review and pairwise and network meta-analysis of randomised controlled trials BMJ. 2022;377:e068882 (Jun 28). Doi: 10.1136/bmj-2021-068882

Key clinical point: Sodium-glucose cotransporter-2 inhibitor (SGLT2i) use was associated with a lower risk for new-onset atrial fibrillation (AF) in patients with type 2 diabetes (T2D) compared with the use of either glucagon-like peptide-1 receptor agonists (GLP-1RA) or dipeptidyl peptidase-4 inhibitors (DPP4i).

Major finding: Use of SGLT2i was associated with a lower risk for new-onset AF compared with the use of DPP4i (hazard ratio [HR] 0.90; P  =  .0028) or GLP-1RA (HR 0.74; P  =  .0007), with no significant difference being observed between the risk associated with GLP-1RA and DPP4i (HR 1.01; P  =  .8980).

Study details: This was a retrospective cohort study that included 344,893, 44,370, and 393,100 patients with T2D and without preexisting AF who were treated with SGLT2i, GLP-1RA, and DPP4i, respectively.

Disclosures: This study was supported by grants from the Ministry of Science and Technology and Chang Gung Memorial Hospital, Linkou, Taiwan. The authors declared no competing interests.

Source: Chan YH et al. The risk of incident atrial fibrillation in patients with type 2 diabetes treated with sodium glucose cotransporter-2 inhibitors, glucagon-like peptide-1 receptor agonists, and dipeptidyl peptidase-4 inhibitors: A nationwide cohort study. Cardiovasc Diabetol. 2022;21:118 (Jun 28). Doi: 10.1186/s12933-022-01549-x

Key clinical point: Sodium-glucose cotransporter-2 inhibitor (SGLT2i) use was associated with a lower risk for new-onset atrial fibrillation (AF) in patients with type 2 diabetes (T2D) compared with the use of either glucagon-like peptide-1 receptor agonists (GLP-1RA) or dipeptidyl peptidase-4 inhibitors (DPP4i).

Major finding: Use of SGLT2i was associated with a lower risk for new-onset AF compared with the use of DPP4i (hazard ratio [HR] 0.90; P  =  .0028) or GLP-1RA (HR 0.74; P  =  .0007), with no significant difference being observed between the risk associated with GLP-1RA and DPP4i (HR 1.01; P  =  .8980).

Study details: This was a retrospective cohort study that included 344,893, 44,370, and 393,100 patients with T2D and without preexisting AF who were treated with SGLT2i, GLP-1RA, and DPP4i, respectively.

Disclosures: This study was supported by grants from the Ministry of Science and Technology and Chang Gung Memorial Hospital, Linkou, Taiwan. The authors declared no competing interests.

Source: Chan YH et al. The risk of incident atrial fibrillation in patients with type 2 diabetes treated with sodium glucose cotransporter-2 inhibitors, glucagon-like peptide-1 receptor agonists, and dipeptidyl peptidase-4 inhibitors: A nationwide cohort study. Cardiovasc Diabetol. 2022;21:118 (Jun 28). Doi: 10.1186/s12933-022-01549-x

Key clinical point: Sodium-glucose cotransporter-2 inhibitor (SGLT2i) use was associated with a lower risk for new-onset atrial fibrillation (AF) in patients with type 2 diabetes (T2D) compared with the use of either glucagon-like peptide-1 receptor agonists (GLP-1RA) or dipeptidyl peptidase-4 inhibitors (DPP4i).

Major finding: Use of SGLT2i was associated with a lower risk for new-onset AF compared with the use of DPP4i (hazard ratio [HR] 0.90; P  =  .0028) or GLP-1RA (HR 0.74; P  =  .0007), with no significant difference being observed between the risk associated with GLP-1RA and DPP4i (HR 1.01; P  =  .8980).

Study details: This was a retrospective cohort study that included 344,893, 44,370, and 393,100 patients with T2D and without preexisting AF who were treated with SGLT2i, GLP-1RA, and DPP4i, respectively.

Disclosures: This study was supported by grants from the Ministry of Science and Technology and Chang Gung Memorial Hospital, Linkou, Taiwan. The authors declared no competing interests.

Source: Chan YH et al. The risk of incident atrial fibrillation in patients with type 2 diabetes treated with sodium glucose cotransporter-2 inhibitors, glucagon-like peptide-1 receptor agonists, and dipeptidyl peptidase-4 inhibitors: A nationwide cohort study. Cardiovasc Diabetol. 2022;21:118 (Jun 28). Doi: 10.1186/s12933-022-01549-x

Key clinical point: Once-weekly semaglutide plus lifestyle intervention significantly improved glucose parameters with a greater likelihood of achieving normoglycemia compared with placebo in patients with baseline prediabetes.

Major finding: Semaglutide vs placebo led to a significant reduction in the glycated hemoglobin level, fasting plasma glucose level, and homeostasis model assessment of insulin resistance (all P < .01), in addition to a significant increase in the proportion of patients experiencing normoglycemia (STEP 1: 84.1% vs 47.8%; STEP 3: 89.5% vs 55.0%; STEP 4: 89.8% vs 70.4%; P < .0001).

Study details: This was a post hoc analysis data of the STEP 1, 3, and 4 trials including 1536 patients with prediabetes who were randomly assigned to received semaglutide or placebo.

Disclosures: The STEP trials were funded by Novo Nordisk. Some authors declared receiving personal fees, speaker fees, advisory or consulting fees, and research funding or other support from various organizations. Three authors are employees and shareholders of Novo Nordisk.

Source: Perreault L et al. Changes in glucose metabolism and glycemic status with once-weekly subcutaneous semaglutide 2.4 mg among participants with prediabetes in the STEP program. Diabetes Care. 2022 (Jul 5). Doi: 10.2337/dc21-1785

Key clinical point: Once-weekly semaglutide plus lifestyle intervention significantly improved glucose parameters with a greater likelihood of achieving normoglycemia compared with placebo in patients with baseline prediabetes.

Major finding: Semaglutide vs placebo led to a significant reduction in the glycated hemoglobin level, fasting plasma glucose level, and homeostasis model assessment of insulin resistance (all P < .01), in addition to a significant increase in the proportion of patients experiencing normoglycemia (STEP 1: 84.1% vs 47.8%; STEP 3: 89.5% vs 55.0%; STEP 4: 89.8% vs 70.4%; P < .0001).

Study details: This was a post hoc analysis data of the STEP 1, 3, and 4 trials including 1536 patients with prediabetes who were randomly assigned to received semaglutide or placebo.

Disclosures: The STEP trials were funded by Novo Nordisk. Some authors declared receiving personal fees, speaker fees, advisory or consulting fees, and research funding or other support from various organizations. Three authors are employees and shareholders of Novo Nordisk.

Source: Perreault L et al. Changes in glucose metabolism and glycemic status with once-weekly subcutaneous semaglutide 2.4 mg among participants with prediabetes in the STEP program. Diabetes Care. 2022 (Jul 5). Doi: 10.2337/dc21-1785

Key clinical point: Once-weekly semaglutide plus lifestyle intervention significantly improved glucose parameters with a greater likelihood of achieving normoglycemia compared with placebo in patients with baseline prediabetes.

Major finding: Semaglutide vs placebo led to a significant reduction in the glycated hemoglobin level, fasting plasma glucose level, and homeostasis model assessment of insulin resistance (all P < .01), in addition to a significant increase in the proportion of patients experiencing normoglycemia (STEP 1: 84.1% vs 47.8%; STEP 3: 89.5% vs 55.0%; STEP 4: 89.8% vs 70.4%; P < .0001).

Study details: This was a post hoc analysis data of the STEP 1, 3, and 4 trials including 1536 patients with prediabetes who were randomly assigned to received semaglutide or placebo.

Disclosures: The STEP trials were funded by Novo Nordisk. Some authors declared receiving personal fees, speaker fees, advisory or consulting fees, and research funding or other support from various organizations. Three authors are employees and shareholders of Novo Nordisk.

Source: Perreault L et al. Changes in glucose metabolism and glycemic status with once-weekly subcutaneous semaglutide 2.4 mg among participants with prediabetes in the STEP program. Diabetes Care. 2022 (Jul 5). Doi: 10.2337/dc21-1785

Key clinical point: Once-weekly efpeglenatide vs placebo led to significant improvements in glycemic control and body weight in patients with type 2 diabetes (T2D), with a safety profile similar to that of glucagon-like peptide 1 receptor agonist.

Major finding: At 30 weeks, 2 mg efpeglenatide (least squares mean difference [LSM] 0.5%; P  =  .0054), 4 mg (LSM 0.8%; P < .0001), and 6 mg (LSM 1.0%; P < .0001) vs placebo led to a significantly greater reduction in glycated hemoglobin levels, with a significant reduction in body weight with 4 and 6 mg efpeglenatide (both P < .05).

Study details: The data come from the AMPLITUDE-M trial including 406 patients with T2D inadequately controlled with diet and exercise alone who were randomly assigned to receive efpeglenatide (n = 304) or placebo (n = 102).

Disclosures: This study was initially sponsored by Sanofi and thereafter, the sponsorship was transferred to Hanmi Pharmaceutical Co., Ltd. Some authors reported serving as advisory board members or speakers and receiving research support from various organizations, including Sanofi. The other authors are employees of and hold stocks in  Sanofi or Hanmi Pharmaceutical Co.

Source: Frias JP et al. Efficacy and safety of once-weekly efpeglenatide monotherapy versus placebo in type 2 diabetes: The AMPLITUDE-M randomized controlled trial. Diabetes Care. 2022;45(7):1592-1600 (Jul 6). Doi:  10.2337/dc21-2656

Key clinical point: Once-weekly efpeglenatide vs placebo led to significant improvements in glycemic control and body weight in patients with type 2 diabetes (T2D), with a safety profile similar to that of glucagon-like peptide 1 receptor agonist.

Major finding: At 30 weeks, 2 mg efpeglenatide (least squares mean difference [LSM] 0.5%; P  =  .0054), 4 mg (LSM 0.8%; P < .0001), and 6 mg (LSM 1.0%; P < .0001) vs placebo led to a significantly greater reduction in glycated hemoglobin levels, with a significant reduction in body weight with 4 and 6 mg efpeglenatide (both P < .05).

Study details: The data come from the AMPLITUDE-M trial including 406 patients with T2D inadequately controlled with diet and exercise alone who were randomly assigned to receive efpeglenatide (n = 304) or placebo (n = 102).

Disclosures: This study was initially sponsored by Sanofi and thereafter, the sponsorship was transferred to Hanmi Pharmaceutical Co., Ltd. Some authors reported serving as advisory board members or speakers and receiving research support from various organizations, including Sanofi. The other authors are employees of and hold stocks in  Sanofi or Hanmi Pharmaceutical Co.

Source: Frias JP et al. Efficacy and safety of once-weekly efpeglenatide monotherapy versus placebo in type 2 diabetes: The AMPLITUDE-M randomized controlled trial. Diabetes Care. 2022;45(7):1592-1600 (Jul 6). Doi:  10.2337/dc21-2656

Key clinical point: Once-weekly efpeglenatide vs placebo led to significant improvements in glycemic control and body weight in patients with type 2 diabetes (T2D), with a safety profile similar to that of glucagon-like peptide 1 receptor agonist.

Major finding: At 30 weeks, 2 mg efpeglenatide (least squares mean difference [LSM] 0.5%; P  =  .0054), 4 mg (LSM 0.8%; P < .0001), and 6 mg (LSM 1.0%; P < .0001) vs placebo led to a significantly greater reduction in glycated hemoglobin levels, with a significant reduction in body weight with 4 and 6 mg efpeglenatide (both P < .05).

Study details: The data come from the AMPLITUDE-M trial including 406 patients with T2D inadequately controlled with diet and exercise alone who were randomly assigned to receive efpeglenatide (n = 304) or placebo (n = 102).

Disclosures: This study was initially sponsored by Sanofi and thereafter, the sponsorship was transferred to Hanmi Pharmaceutical Co., Ltd. Some authors reported serving as advisory board members or speakers and receiving research support from various organizations, including Sanofi. The other authors are employees of and hold stocks in  Sanofi or Hanmi Pharmaceutical Co.

Source: Frias JP et al. Efficacy and safety of once-weekly efpeglenatide monotherapy versus placebo in type 2 diabetes: The AMPLITUDE-M randomized controlled trial. Diabetes Care. 2022;45(7):1592-1600 (Jul 6). Doi:  10.2337/dc21-2656

Adding to a growing body of evidence that elevated remnant cholesterol (remnant-C) provides additional and independent risk prediction for major cardiovascular events (MACE), a new analysis has this shown this biomarker has prognostic value specifically in patients with type 2 diabetes (T2D).

In a post hoc analysis of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, each standard-deviation increase in remnant-C was associated with a 7% increased risk in MACE (P = .004) after adjustment for several risk factors including other cholesterol values.

“In type 2 diabetes, remnant-C levels are associated with MACE regardless of LDL-C,” reported a team of investigators led by Liyao Fu, MD, Second Xiangya Hospital of Central South University, Changsha, China .

Remnant-C is one component of triglyceride-rich lipoproteins. Within triglyceride-rich lipoproteins, remnant-C has become a major focus of efforts to explain cardiovascular (CV) residual risk, according to the investigators.

Residual risk is a term used to explain why cardiovascular events occur after all known modifiable factors, such as LDL cholesterol (LDL-C), are controlled.

“Our primary findings indicate that baseline estimated remnant-C levels were associated with MACE regardless of clinical phenotypes, lifestyle confounders relative to CV risk, and lipid-lowering treatment,” said the authors of the analysis.

In the post hoc analysis of the ACCORD trial, which evaluated the effects of intensive glucose lowering in T2D more than 10 years ago, there were data on remnant-C over a median of 8.8 years of follow-up in 9,650 T2D patients. Over this period, 1,815 (17.8%) developed MACE.

Multiple analyses support prognostic value of remnant-C

In addition to the 7% rise in MACE for each standard-deviation increase in remnant-C when calculated as a continuous variable, other analyses told the same story.

This included an assessment by remnant-C tertiles. Not only was there a significant trend (P < .001) for greater risk with each higher baseline tertile of remnant-C, those in the highest tertile had a 38% greater risk of MACE relative to those in the lowest tertile (hazard ratio, 1.38; P < .001) after adjustment for confounders.

The same pattern was seen for several components of MACE, such as CV death and nonfatal myocardial infarction, when remnant-C tertiles were compared.

Visit-to-visit variability in remnant-C over the course of follow-up was also associated with greater risk of MACE. In logarithmic calculations, the risk of MACE climbed about 40% across all three models of risk adjustment. These models included adjustments for different sets of confounders, such as sex, age, blood pressure, CV disease history, and glucose levels. On an unadjusted basis, the risk was increased about 50% (HR, 1.52; P < .001).

For visit-to-visit variability in remnant-C, the greatest effect was on risk of nonfatal MI across models. In model 3, for example, which adjusted for the most confounders, the risk was nearly doubled (HR, 1.92; P < .001). In contrast, there did not appear to be a link between visit-to-visit variability and nonfatal stroke.

In a discordant analysis that was conducted to examine the relative risk of remnant-C independent of LDL-C, those who had a remnant-C level of at least 31 mg/dL were found to have a higher risk of MACE regardless of LDL-C level. Yet, the risk was higher if both remnant-C and LDL-C were elevated. For example, the risk was increased 22% for those with LDL-C at or below 100 mg/dL and remnant-C levels of at least 31 mg/dL (HR, 1.22; P = .015) but climbed to 37% for those with LDL-C above 100 mg/dL if remnant-C was at least 31 mg/dL (HR, 1.38; P = .007).
 

Remnant-C shows prognostic value in other risk groups

Although this study suggests an important prognostic value for remnant-C in T2D, there are numerous studies suggesting that it has prognostic value in other risk groups, such as those with a history of CV disease. This includes a study published earlier this year with 10 years of follow-up in 41,928 patients in Denmark. When combined with other risk factors, remnant-C substantially improved the accuracy of risk of events over time.

The investigators from this previous study, like the new study in patients with T2D, predict that remnant-C will be eventually included in guidelines.

According to Shi Tai, MD, a coauthor of the T2D study, remnant-C “may allow for the development of specific preventive and therapeutic approaches” to CV risk in patients with T2D.

T2D patients “with elevated plasma remnant-C levels represent a special population that deserves more attention regarding residual risk,” said Dr. Tai of the department of cardiovascular medicine at the Hospital of South Central China.
 

Great interest, but ready for guidelines?

This is an important direction of ongoing research, according to Christie M. Ballantyne, MD, professor of medicine, Baylor College of Medicine, Houston.

“There is a great deal of interest from both clinicians and trialists to find a simple way to identify patients with high residual risk who are on statin therapy,” he said. He thinks remnant-C has promise in this regard.

“Remnant-C is not in current guidelines,” he said in an interview, but he suggested that there is now a substantial body of evidence to suggest that it might be added if validated in further studies.

“Remnant-C is easy to calculate and may be helpful in practice now to identify patients who need more aggressive therapy to reduce risk and may be useful to identify patients for clinical trials who will benefit from new therapies that are in development,” he said.

However, the clinical relevance of therapies addressed at triglyceride-rich lipoproteins in general or their components, including triglycerides or remnant-C, has never been demonstrated, pointed out Peter W.F. Wilson, MD, PhD.

“Higher fasting or nonfasting triglyceride levels or their surrogates have been shown to be associated with increased risk for cardiovascular disease events in observational studies, but the importance of such measurements in persons already treated with very aggressive LDL-C lowering therapy is not known,” commented Dr. Wilson, director of epidemiology and genomic medicine, Emory School of Medicine, Atlanta.

Dr. Wilson was the coauthor of an editorial that accompanied the previously published Danish study of remnant-C. In his editorial, he suggested that remnant-C has promise for better understanding residual risk, but when contacted about these latest data he emphasized a lack of support so far for clinical relevance.

“Unfortunately, clinical trials have generally not shown that triglyceride lowering [to favorably alter remnant-C] in this situation favorably affects the risk of CV disease events,” he said in an interview. This does not preclude remnant-C as a targetable risk factor, but these data are needed.

Dr. Fu, Dr. Tai, and Dr. Wilson report no potential conflicts of interest. Dr. Ballantyne has financial relationships with more than 25 pharmaceutical companies, including several that produce products employed for the treatment of lipid abnormalities.

Adding to a growing body of evidence that elevated remnant cholesterol (remnant-C) provides additional and independent risk prediction for major cardiovascular events (MACE), a new analysis has this shown this biomarker has prognostic value specifically in patients with type 2 diabetes (T2D).

In a post hoc analysis of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, each standard-deviation increase in remnant-C was associated with a 7% increased risk in MACE (P = .004) after adjustment for several risk factors including other cholesterol values.

“In type 2 diabetes, remnant-C levels are associated with MACE regardless of LDL-C,” reported a team of investigators led by Liyao Fu, MD, Second Xiangya Hospital of Central South University, Changsha, China .

Remnant-C is one component of triglyceride-rich lipoproteins. Within triglyceride-rich lipoproteins, remnant-C has become a major focus of efforts to explain cardiovascular (CV) residual risk, according to the investigators.

Residual risk is a term used to explain why cardiovascular events occur after all known modifiable factors, such as LDL cholesterol (LDL-C), are controlled.

“Our primary findings indicate that baseline estimated remnant-C levels were associated with MACE regardless of clinical phenotypes, lifestyle confounders relative to CV risk, and lipid-lowering treatment,” said the authors of the analysis.

In the post hoc analysis of the ACCORD trial, which evaluated the effects of intensive glucose lowering in T2D more than 10 years ago, there were data on remnant-C over a median of 8.8 years of follow-up in 9,650 T2D patients. Over this period, 1,815 (17.8%) developed MACE.

Multiple analyses support prognostic value of remnant-C

In addition to the 7% rise in MACE for each standard-deviation increase in remnant-C when calculated as a continuous variable, other analyses told the same story.

This included an assessment by remnant-C tertiles. Not only was there a significant trend (P < .001) for greater risk with each higher baseline tertile of remnant-C, those in the highest tertile had a 38% greater risk of MACE relative to those in the lowest tertile (hazard ratio, 1.38; P < .001) after adjustment for confounders.

The same pattern was seen for several components of MACE, such as CV death and nonfatal myocardial infarction, when remnant-C tertiles were compared.

Visit-to-visit variability in remnant-C over the course of follow-up was also associated with greater risk of MACE. In logarithmic calculations, the risk of MACE climbed about 40% across all three models of risk adjustment. These models included adjustments for different sets of confounders, such as sex, age, blood pressure, CV disease history, and glucose levels. On an unadjusted basis, the risk was increased about 50% (HR, 1.52; P < .001).

For visit-to-visit variability in remnant-C, the greatest effect was on risk of nonfatal MI across models. In model 3, for example, which adjusted for the most confounders, the risk was nearly doubled (HR, 1.92; P < .001). In contrast, there did not appear to be a link between visit-to-visit variability and nonfatal stroke.

In a discordant analysis that was conducted to examine the relative risk of remnant-C independent of LDL-C, those who had a remnant-C level of at least 31 mg/dL were found to have a higher risk of MACE regardless of LDL-C level. Yet, the risk was higher if both remnant-C and LDL-C were elevated. For example, the risk was increased 22% for those with LDL-C at or below 100 mg/dL and remnant-C levels of at least 31 mg/dL (HR, 1.22; P = .015) but climbed to 37% for those with LDL-C above 100 mg/dL if remnant-C was at least 31 mg/dL (HR, 1.38; P = .007).
 

Remnant-C shows prognostic value in other risk groups

Although this study suggests an important prognostic value for remnant-C in T2D, there are numerous studies suggesting that it has prognostic value in other risk groups, such as those with a history of CV disease. This includes a study published earlier this year with 10 years of follow-up in 41,928 patients in Denmark. When combined with other risk factors, remnant-C substantially improved the accuracy of risk of events over time.

The investigators from this previous study, like the new study in patients with T2D, predict that remnant-C will be eventually included in guidelines.

According to Shi Tai, MD, a coauthor of the T2D study, remnant-C “may allow for the development of specific preventive and therapeutic approaches” to CV risk in patients with T2D.

T2D patients “with elevated plasma remnant-C levels represent a special population that deserves more attention regarding residual risk,” said Dr. Tai of the department of cardiovascular medicine at the Hospital of South Central China.
 

Great interest, but ready for guidelines?

This is an important direction of ongoing research, according to Christie M. Ballantyne, MD, professor of medicine, Baylor College of Medicine, Houston.

“There is a great deal of interest from both clinicians and trialists to find a simple way to identify patients with high residual risk who are on statin therapy,” he said. He thinks remnant-C has promise in this regard.

“Remnant-C is not in current guidelines,” he said in an interview, but he suggested that there is now a substantial body of evidence to suggest that it might be added if validated in further studies.

“Remnant-C is easy to calculate and may be helpful in practice now to identify patients who need more aggressive therapy to reduce risk and may be useful to identify patients for clinical trials who will benefit from new therapies that are in development,” he said.

However, the clinical relevance of therapies addressed at triglyceride-rich lipoproteins in general or their components, including triglycerides or remnant-C, has never been demonstrated, pointed out Peter W.F. Wilson, MD, PhD.

“Higher fasting or nonfasting triglyceride levels or their surrogates have been shown to be associated with increased risk for cardiovascular disease events in observational studies, but the importance of such measurements in persons already treated with very aggressive LDL-C lowering therapy is not known,” commented Dr. Wilson, director of epidemiology and genomic medicine, Emory School of Medicine, Atlanta.

Dr. Wilson was the coauthor of an editorial that accompanied the previously published Danish study of remnant-C. In his editorial, he suggested that remnant-C has promise for better understanding residual risk, but when contacted about these latest data he emphasized a lack of support so far for clinical relevance.

“Unfortunately, clinical trials have generally not shown that triglyceride lowering [to favorably alter remnant-C] in this situation favorably affects the risk of CV disease events,” he said in an interview. This does not preclude remnant-C as a targetable risk factor, but these data are needed.

Dr. Fu, Dr. Tai, and Dr. Wilson report no potential conflicts of interest. Dr. Ballantyne has financial relationships with more than 25 pharmaceutical companies, including several that produce products employed for the treatment of lipid abnormalities.

Adding to a growing body of evidence that elevated remnant cholesterol (remnant-C) provides additional and independent risk prediction for major cardiovascular events (MACE), a new analysis has this shown this biomarker has prognostic value specifically in patients with type 2 diabetes (T2D).

In a post hoc analysis of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, each standard-deviation increase in remnant-C was associated with a 7% increased risk in MACE (P = .004) after adjustment for several risk factors including other cholesterol values.

“In type 2 diabetes, remnant-C levels are associated with MACE regardless of LDL-C,” reported a team of investigators led by Liyao Fu, MD, Second Xiangya Hospital of Central South University, Changsha, China .

Remnant-C is one component of triglyceride-rich lipoproteins. Within triglyceride-rich lipoproteins, remnant-C has become a major focus of efforts to explain cardiovascular (CV) residual risk, according to the investigators.

Residual risk is a term used to explain why cardiovascular events occur after all known modifiable factors, such as LDL cholesterol (LDL-C), are controlled.

“Our primary findings indicate that baseline estimated remnant-C levels were associated with MACE regardless of clinical phenotypes, lifestyle confounders relative to CV risk, and lipid-lowering treatment,” said the authors of the analysis.

In the post hoc analysis of the ACCORD trial, which evaluated the effects of intensive glucose lowering in T2D more than 10 years ago, there were data on remnant-C over a median of 8.8 years of follow-up in 9,650 T2D patients. Over this period, 1,815 (17.8%) developed MACE.

Multiple analyses support prognostic value of remnant-C

In addition to the 7% rise in MACE for each standard-deviation increase in remnant-C when calculated as a continuous variable, other analyses told the same story.

This included an assessment by remnant-C tertiles. Not only was there a significant trend (P < .001) for greater risk with each higher baseline tertile of remnant-C, those in the highest tertile had a 38% greater risk of MACE relative to those in the lowest tertile (hazard ratio, 1.38; P < .001) after adjustment for confounders.

The same pattern was seen for several components of MACE, such as CV death and nonfatal myocardial infarction, when remnant-C tertiles were compared.

Visit-to-visit variability in remnant-C over the course of follow-up was also associated with greater risk of MACE. In logarithmic calculations, the risk of MACE climbed about 40% across all three models of risk adjustment. These models included adjustments for different sets of confounders, such as sex, age, blood pressure, CV disease history, and glucose levels. On an unadjusted basis, the risk was increased about 50% (HR, 1.52; P < .001).

For visit-to-visit variability in remnant-C, the greatest effect was on risk of nonfatal MI across models. In model 3, for example, which adjusted for the most confounders, the risk was nearly doubled (HR, 1.92; P < .001). In contrast, there did not appear to be a link between visit-to-visit variability and nonfatal stroke.

In a discordant analysis that was conducted to examine the relative risk of remnant-C independent of LDL-C, those who had a remnant-C level of at least 31 mg/dL were found to have a higher risk of MACE regardless of LDL-C level. Yet, the risk was higher if both remnant-C and LDL-C were elevated. For example, the risk was increased 22% for those with LDL-C at or below 100 mg/dL and remnant-C levels of at least 31 mg/dL (HR, 1.22; P = .015) but climbed to 37% for those with LDL-C above 100 mg/dL if remnant-C was at least 31 mg/dL (HR, 1.38; P = .007).
 

Remnant-C shows prognostic value in other risk groups

Although this study suggests an important prognostic value for remnant-C in T2D, there are numerous studies suggesting that it has prognostic value in other risk groups, such as those with a history of CV disease. This includes a study published earlier this year with 10 years of follow-up in 41,928 patients in Denmark. When combined with other risk factors, remnant-C substantially improved the accuracy of risk of events over time.

The investigators from this previous study, like the new study in patients with T2D, predict that remnant-C will be eventually included in guidelines.

According to Shi Tai, MD, a coauthor of the T2D study, remnant-C “may allow for the development of specific preventive and therapeutic approaches” to CV risk in patients with T2D.

T2D patients “with elevated plasma remnant-C levels represent a special population that deserves more attention regarding residual risk,” said Dr. Tai of the department of cardiovascular medicine at the Hospital of South Central China.
 

Great interest, but ready for guidelines?

This is an important direction of ongoing research, according to Christie M. Ballantyne, MD, professor of medicine, Baylor College of Medicine, Houston.

“There is a great deal of interest from both clinicians and trialists to find a simple way to identify patients with high residual risk who are on statin therapy,” he said. He thinks remnant-C has promise in this regard.

“Remnant-C is not in current guidelines,” he said in an interview, but he suggested that there is now a substantial body of evidence to suggest that it might be added if validated in further studies.

“Remnant-C is easy to calculate and may be helpful in practice now to identify patients who need more aggressive therapy to reduce risk and may be useful to identify patients for clinical trials who will benefit from new therapies that are in development,” he said.

However, the clinical relevance of therapies addressed at triglyceride-rich lipoproteins in general or their components, including triglycerides or remnant-C, has never been demonstrated, pointed out Peter W.F. Wilson, MD, PhD.

“Higher fasting or nonfasting triglyceride levels or their surrogates have been shown to be associated with increased risk for cardiovascular disease events in observational studies, but the importance of such measurements in persons already treated with very aggressive LDL-C lowering therapy is not known,” commented Dr. Wilson, director of epidemiology and genomic medicine, Emory School of Medicine, Atlanta.

Dr. Wilson was the coauthor of an editorial that accompanied the previously published Danish study of remnant-C. In his editorial, he suggested that remnant-C has promise for better understanding residual risk, but when contacted about these latest data he emphasized a lack of support so far for clinical relevance.

“Unfortunately, clinical trials have generally not shown that triglyceride lowering [to favorably alter remnant-C] in this situation favorably affects the risk of CV disease events,” he said in an interview. This does not preclude remnant-C as a targetable risk factor, but these data are needed.

Dr. Fu, Dr. Tai, and Dr. Wilson report no potential conflicts of interest. Dr. Ballantyne has financial relationships with more than 25 pharmaceutical companies, including several that produce products employed for the treatment of lipid abnormalities.

U.S. Medicare beneficiaries with type 2 diabetes who had health coverage through a Medicare Advantage (MA) plan received treatment with an sodium-glucose cotransporter 2 inhibitor or glucagonlike peptide–1 receptor agonist significantly less often than patients with traditional fee-for-service (FFS) Medicare coverage in 2014-2019, according to a study of more than 411,000 patients.

“MA beneficiaries had modestly but significantly poorer intermediate health outcomes and were less likely to be treated with newer evidence-based antihyperglycemic therapies, compared with Medicare FFS beneficiaries,” concluded Utibe R. Essien, MD, and coauthors in a study published in Diabetes Care.

The report comes as the U.S. Congress is looking closely at the MA program and evidence that insurance companies that provide these policies sometimes impose inappropriate barriers on enrolled beneficiaries by denying or limiting access to treatments and interventions in ways that run counter to Medicare’s coverage policies.

According to Representative Diana DeGette (D-Colo.), who chaired a hearing on MA plans on June 28 by the House of Representatives’ Energy and Commerce Subcommittee on Oversight and Investigations, beneficiaries who are covered through an MA plan “do not always get the care that they are entitled to.”

The study by Dr. Essien and colleagues also documents some positives of care delivered through MA plans for patients with type 2 diabetes, compared with what FFS Medicare beneficiaries generally receive, such as significantly higher rates of screening for nephropathy and ophthalmologic disorders, and foot examinations.

But the apparently dampened use of SGLT2 inhibitors and GLP-1 receptor agonists among MA beneficiaries stand out as notable shortcomings, Dr. Essien maintained.
 

Cost containment may limit use

“The differences in health outcomes and in treatments in MA plans are important to highlight,” Dr. Essien said in an interview. “We worry that the cost-containment challenges [associated with MA plans] may be limiting use of these newer treatments.”

The study was based on 2014-2019 data from the Diabetes Collaborative Registry, which collects information from more than 5,000 U.S. clinicians whose practices include patients with diabetes, as well as claims data recorded by the Centers for Medicare and Medicaid Services during 2014-2017.

The main analysis focused on 345,911 Medicare beneficiaries with diabetes, which included 34% with MA coverage and 66% with FFS coverage. The two subgroups had similar ages, about 75 years old, and roughly half were women in both subgroups. The rate at which both subgroups received statin treatment was nearly the same: 72% for those with MA coverage and 71% for those with FFS Medicare.

But MA beneficiaries differed from those with FFS coverage in several other ways. MA beneficiaries had a higher prevalence of Medicaid eligibility than the FFS group (20% vs 12%) and lower rates of consultations with cardiologists (41% vs. 45%) or endocrinologists (7% vs. 10%).

Some of the positive differences in the care received by MA beneficiaries, compared with FFS beneficiaries, after adjustment for potential clinical and sociodemographic confounders, included:

• Screening for nephropathy, at a significant 14% higher relative rate.
• Screening for ophthalmologic disorders, at a significant 8% higher relative rate.
• Undergoing a diabetic foot examination, at a significant 13% higher relative rate.
• Receiving smoking-cessation counseling, at a significant 5% higher relative rate.
• Receiving treatment with an ACE inhibitor or angiotensin-receptor blocker (87% vs. 81%).
• More consistently receiving treatment with metformin, with rates of 72% versus 69% in 2017.

However, these positive differences were accompanied by these relative shortcomings for those with MA, compared with FFS coverage:

• Lower rates of treatment with an SGLT2 inhibitor (5.4% vs. 6.7%), a significant 9% relative difference after adjustment.
• Lower rates of treatment with a GLP-1 agonist (6.9% vs. 9.0%), a significant 20% relative difference after adjustment.
• Higher average levels of LDL cholesterol (81.5 vs. 78.9 mg/dL), a significantly higher average hemoglobin A1c level (7.1% vs. 7.0%), and a trend toward a lower prevalence of blood pressure control (70.3% vs. 71.5%).

Researchers also highlight that the lower rate at which people with MA coverage received SGLT2 inhibitors or GLP-1 agonists was consistent in patients with established cardiovascular or kidney disease, for whom these agents are particularly recommended.

In addition, a secondary analysis of data for another 65,000 Medicare beneficiaries in 2018 and 2019 showed the disparity in use of agents from these two drug classes continued.
 

Low systemic use of SGLT2 inhibitors, GLP-1 agonists

Dr. Essien acknowledged that, even in people with FFS Medicare coverage, use of SGLT2 inhibitors and GLP-1 agonists was low, but the difference between those with MA coverage is “important.”

Researchers offered four factors that might drive reduced prescribing of agents from these two classes for patients with type 2 diabetes with MA coverage: cost-containment strategies put in place by MA plans; the lower rate of consultations with specialists (cardiologists and endocrinologists); possible exclusion of clinicians from MA provider networks who tend to prescribe these higher-price agents; and lower household incomes of people with MA plans, which may lead to cost-related nonadherence.

Most SGLT2 inhibitors have an average retail cost of about $6,000/year, and some GLP-1 agonists cost more than $10,000/year.

In general, MA coverage includes more oversight of care and its cost than occurs with FFS coverage, noted Dr. Essien, an internal medicine physician at the University of Pittsburgh and a researcher at the Center for Health Equity Research and Promotion of the VA Pittsburgh Healthcare System.

“Incentives for using these more expensive treatments may not be there in MA plans,” he explained. Overcoming cost-related barriers is a challenge that will require “bold policy changes,” as well as better education of clinicians so they make correct treatment decisions, and of patients to resolve possible concerns about treatment safety.

Rep. DeGette hinted during her remarks at the June hearing that policy changes may be coming from Congress.

“Our seniors and their doctors should not be required to jump through numerous hoops to get coverage for straightforward and medically necessary procedures,” she said.

The study received no commercial funding. Dr. Essien reported no relevant financial relationships.

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

U.S. Medicare beneficiaries with type 2 diabetes who had health coverage through a Medicare Advantage (MA) plan received treatment with an sodium-glucose cotransporter 2 inhibitor or glucagonlike peptide–1 receptor agonist significantly less often than patients with traditional fee-for-service (FFS) Medicare coverage in 2014-2019, according to a study of more than 411,000 patients.

“MA beneficiaries had modestly but significantly poorer intermediate health outcomes and were less likely to be treated with newer evidence-based antihyperglycemic therapies, compared with Medicare FFS beneficiaries,” concluded Utibe R. Essien, MD, and coauthors in a study published in Diabetes Care.

The report comes as the U.S. Congress is looking closely at the MA program and evidence that insurance companies that provide these policies sometimes impose inappropriate barriers on enrolled beneficiaries by denying or limiting access to treatments and interventions in ways that run counter to Medicare’s coverage policies.

According to Representative Diana DeGette (D-Colo.), who chaired a hearing on MA plans on June 28 by the House of Representatives’ Energy and Commerce Subcommittee on Oversight and Investigations, beneficiaries who are covered through an MA plan “do not always get the care that they are entitled to.”

The study by Dr. Essien and colleagues also documents some positives of care delivered through MA plans for patients with type 2 diabetes, compared with what FFS Medicare beneficiaries generally receive, such as significantly higher rates of screening for nephropathy and ophthalmologic disorders, and foot examinations.

But the apparently dampened use of SGLT2 inhibitors and GLP-1 receptor agonists among MA beneficiaries stand out as notable shortcomings, Dr. Essien maintained.
 

Cost containment may limit use

“The differences in health outcomes and in treatments in MA plans are important to highlight,” Dr. Essien said in an interview. “We worry that the cost-containment challenges [associated with MA plans] may be limiting use of these newer treatments.”

The study was based on 2014-2019 data from the Diabetes Collaborative Registry, which collects information from more than 5,000 U.S. clinicians whose practices include patients with diabetes, as well as claims data recorded by the Centers for Medicare and Medicaid Services during 2014-2017.

The main analysis focused on 345,911 Medicare beneficiaries with diabetes, which included 34% with MA coverage and 66% with FFS coverage. The two subgroups had similar ages, about 75 years old, and roughly half were women in both subgroups. The rate at which both subgroups received statin treatment was nearly the same: 72% for those with MA coverage and 71% for those with FFS Medicare.

But MA beneficiaries differed from those with FFS coverage in several other ways. MA beneficiaries had a higher prevalence of Medicaid eligibility than the FFS group (20% vs 12%) and lower rates of consultations with cardiologists (41% vs. 45%) or endocrinologists (7% vs. 10%).

Some of the positive differences in the care received by MA beneficiaries, compared with FFS beneficiaries, after adjustment for potential clinical and sociodemographic confounders, included:

• Screening for nephropathy, at a significant 14% higher relative rate.
• Screening for ophthalmologic disorders, at a significant 8% higher relative rate.
• Undergoing a diabetic foot examination, at a significant 13% higher relative rate.
• Receiving smoking-cessation counseling, at a significant 5% higher relative rate.
• Receiving treatment with an ACE inhibitor or angiotensin-receptor blocker (87% vs. 81%).
• More consistently receiving treatment with metformin, with rates of 72% versus 69% in 2017.

However, these positive differences were accompanied by these relative shortcomings for those with MA, compared with FFS coverage:

• Lower rates of treatment with an SGLT2 inhibitor (5.4% vs. 6.7%), a significant 9% relative difference after adjustment.
• Lower rates of treatment with a GLP-1 agonist (6.9% vs. 9.0%), a significant 20% relative difference after adjustment.
• Higher average levels of LDL cholesterol (81.5 vs. 78.9 mg/dL), a significantly higher average hemoglobin A1c level (7.1% vs. 7.0%), and a trend toward a lower prevalence of blood pressure control (70.3% vs. 71.5%).

Researchers also highlight that the lower rate at which people with MA coverage received SGLT2 inhibitors or GLP-1 agonists was consistent in patients with established cardiovascular or kidney disease, for whom these agents are particularly recommended.

In addition, a secondary analysis of data for another 65,000 Medicare beneficiaries in 2018 and 2019 showed the disparity in use of agents from these two drug classes continued.
 

Low systemic use of SGLT2 inhibitors, GLP-1 agonists

Dr. Essien acknowledged that, even in people with FFS Medicare coverage, use of SGLT2 inhibitors and GLP-1 agonists was low, but the difference between those with MA coverage is “important.”

Researchers offered four factors that might drive reduced prescribing of agents from these two classes for patients with type 2 diabetes with MA coverage: cost-containment strategies put in place by MA plans; the lower rate of consultations with specialists (cardiologists and endocrinologists); possible exclusion of clinicians from MA provider networks who tend to prescribe these higher-price agents; and lower household incomes of people with MA plans, which may lead to cost-related nonadherence.

Most SGLT2 inhibitors have an average retail cost of about $6,000/year, and some GLP-1 agonists cost more than $10,000/year.

In general, MA coverage includes more oversight of care and its cost than occurs with FFS coverage, noted Dr. Essien, an internal medicine physician at the University of Pittsburgh and a researcher at the Center for Health Equity Research and Promotion of the VA Pittsburgh Healthcare System.

“Incentives for using these more expensive treatments may not be there in MA plans,” he explained. Overcoming cost-related barriers is a challenge that will require “bold policy changes,” as well as better education of clinicians so they make correct treatment decisions, and of patients to resolve possible concerns about treatment safety.

Rep. DeGette hinted during her remarks at the June hearing that policy changes may be coming from Congress.

“Our seniors and their doctors should not be required to jump through numerous hoops to get coverage for straightforward and medically necessary procedures,” she said.

The study received no commercial funding. Dr. Essien reported no relevant financial relationships.

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

U.S. Medicare beneficiaries with type 2 diabetes who had health coverage through a Medicare Advantage (MA) plan received treatment with an sodium-glucose cotransporter 2 inhibitor or glucagonlike peptide–1 receptor agonist significantly less often than patients with traditional fee-for-service (FFS) Medicare coverage in 2014-2019, according to a study of more than 411,000 patients.

“MA beneficiaries had modestly but significantly poorer intermediate health outcomes and were less likely to be treated with newer evidence-based antihyperglycemic therapies, compared with Medicare FFS beneficiaries,” concluded Utibe R. Essien, MD, and coauthors in a study published in Diabetes Care.

The report comes as the U.S. Congress is looking closely at the MA program and evidence that insurance companies that provide these policies sometimes impose inappropriate barriers on enrolled beneficiaries by denying or limiting access to treatments and interventions in ways that run counter to Medicare’s coverage policies.

According to Representative Diana DeGette (D-Colo.), who chaired a hearing on MA plans on June 28 by the House of Representatives’ Energy and Commerce Subcommittee on Oversight and Investigations, beneficiaries who are covered through an MA plan “do not always get the care that they are entitled to.”

The study by Dr. Essien and colleagues also documents some positives of care delivered through MA plans for patients with type 2 diabetes, compared with what FFS Medicare beneficiaries generally receive, such as significantly higher rates of screening for nephropathy and ophthalmologic disorders, and foot examinations.

But the apparently dampened use of SGLT2 inhibitors and GLP-1 receptor agonists among MA beneficiaries stand out as notable shortcomings, Dr. Essien maintained.
 

Cost containment may limit use

“The differences in health outcomes and in treatments in MA plans are important to highlight,” Dr. Essien said in an interview. “We worry that the cost-containment challenges [associated with MA plans] may be limiting use of these newer treatments.”

The study was based on 2014-2019 data from the Diabetes Collaborative Registry, which collects information from more than 5,000 U.S. clinicians whose practices include patients with diabetes, as well as claims data recorded by the Centers for Medicare and Medicaid Services during 2014-2017.

The main analysis focused on 345,911 Medicare beneficiaries with diabetes, which included 34% with MA coverage and 66% with FFS coverage. The two subgroups had similar ages, about 75 years old, and roughly half were women in both subgroups. The rate at which both subgroups received statin treatment was nearly the same: 72% for those with MA coverage and 71% for those with FFS Medicare.

But MA beneficiaries differed from those with FFS coverage in several other ways. MA beneficiaries had a higher prevalence of Medicaid eligibility than the FFS group (20% vs 12%) and lower rates of consultations with cardiologists (41% vs. 45%) or endocrinologists (7% vs. 10%).

Some of the positive differences in the care received by MA beneficiaries, compared with FFS beneficiaries, after adjustment for potential clinical and sociodemographic confounders, included:

• Screening for nephropathy, at a significant 14% higher relative rate.
• Screening for ophthalmologic disorders, at a significant 8% higher relative rate.
• Undergoing a diabetic foot examination, at a significant 13% higher relative rate.
• Receiving smoking-cessation counseling, at a significant 5% higher relative rate.
• Receiving treatment with an ACE inhibitor or angiotensin-receptor blocker (87% vs. 81%).
• More consistently receiving treatment with metformin, with rates of 72% versus 69% in 2017.

However, these positive differences were accompanied by these relative shortcomings for those with MA, compared with FFS coverage:

• Lower rates of treatment with an SGLT2 inhibitor (5.4% vs. 6.7%), a significant 9% relative difference after adjustment.
• Lower rates of treatment with a GLP-1 agonist (6.9% vs. 9.0%), a significant 20% relative difference after adjustment.
• Higher average levels of LDL cholesterol (81.5 vs. 78.9 mg/dL), a significantly higher average hemoglobin A1c level (7.1% vs. 7.0%), and a trend toward a lower prevalence of blood pressure control (70.3% vs. 71.5%).

Researchers also highlight that the lower rate at which people with MA coverage received SGLT2 inhibitors or GLP-1 agonists was consistent in patients with established cardiovascular or kidney disease, for whom these agents are particularly recommended.

In addition, a secondary analysis of data for another 65,000 Medicare beneficiaries in 2018 and 2019 showed the disparity in use of agents from these two drug classes continued.
 

Low systemic use of SGLT2 inhibitors, GLP-1 agonists

Dr. Essien acknowledged that, even in people with FFS Medicare coverage, use of SGLT2 inhibitors and GLP-1 agonists was low, but the difference between those with MA coverage is “important.”

Researchers offered four factors that might drive reduced prescribing of agents from these two classes for patients with type 2 diabetes with MA coverage: cost-containment strategies put in place by MA plans; the lower rate of consultations with specialists (cardiologists and endocrinologists); possible exclusion of clinicians from MA provider networks who tend to prescribe these higher-price agents; and lower household incomes of people with MA plans, which may lead to cost-related nonadherence.

Most SGLT2 inhibitors have an average retail cost of about $6,000/year, and some GLP-1 agonists cost more than $10,000/year.

In general, MA coverage includes more oversight of care and its cost than occurs with FFS coverage, noted Dr. Essien, an internal medicine physician at the University of Pittsburgh and a researcher at the Center for Health Equity Research and Promotion of the VA Pittsburgh Healthcare System.

“Incentives for using these more expensive treatments may not be there in MA plans,” he explained. Overcoming cost-related barriers is a challenge that will require “bold policy changes,” as well as better education of clinicians so they make correct treatment decisions, and of patients to resolve possible concerns about treatment safety.

Rep. DeGette hinted during her remarks at the June hearing that policy changes may be coming from Congress.

“Our seniors and their doctors should not be required to jump through numerous hoops to get coverage for straightforward and medically necessary procedures,” she said.

The study received no commercial funding. Dr. Essien reported no relevant financial relationships.

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