Type 2 Diabetes ICYMI

Key clinical point: The sarcopenia index (SI; serum creatinine/serum cystatin C ratio) is significantly associated with the prevalence of subclinical atherosclerosis in patients with type 2 diabetes mellitus (T2D).

Major finding: After adjusting for all confounders, SI was significantly associated with the prevalence of subclinical atherosclerosis (adjusted odds ratio 0.95; P  =  .015).

Study details: The data come from a cross-sectional study of 174 patients with T2D, of which 43.7% were diagnosed with subclinical atherosclerosis.

Disclosures: The study received no specific funding. Some authors declared receiving honoraria, personal fees, r research grants from various sources.

Source: Hashimoto Y et al. Relationship between serum creatinine to cystatin C ratio and subclinical atherosclerosis in patients with type 2 diabetes. BMJ Open Diabetes Res Care. 2022;10:e002910 (Jun 23). Doi: 10.1136/bmjdrc-2022-002910

Key clinical point: The sarcopenia index (SI; serum creatinine/serum cystatin C ratio) is significantly associated with the prevalence of subclinical atherosclerosis in patients with type 2 diabetes mellitus (T2D).

Major finding: After adjusting for all confounders, SI was significantly associated with the prevalence of subclinical atherosclerosis (adjusted odds ratio 0.95; P  =  .015).

Study details: The data come from a cross-sectional study of 174 patients with T2D, of which 43.7% were diagnosed with subclinical atherosclerosis.

Disclosures: The study received no specific funding. Some authors declared receiving honoraria, personal fees, r research grants from various sources.

Source: Hashimoto Y et al. Relationship between serum creatinine to cystatin C ratio and subclinical atherosclerosis in patients with type 2 diabetes. BMJ Open Diabetes Res Care. 2022;10:e002910 (Jun 23). Doi: 10.1136/bmjdrc-2022-002910

Key clinical point: The sarcopenia index (SI; serum creatinine/serum cystatin C ratio) is significantly associated with the prevalence of subclinical atherosclerosis in patients with type 2 diabetes mellitus (T2D).

Major finding: After adjusting for all confounders, SI was significantly associated with the prevalence of subclinical atherosclerosis (adjusted odds ratio 0.95; P  =  .015).

Study details: The data come from a cross-sectional study of 174 patients with T2D, of which 43.7% were diagnosed with subclinical atherosclerosis.

Disclosures: The study received no specific funding. Some authors declared receiving honoraria, personal fees, r research grants from various sources.

Source: Hashimoto Y et al. Relationship between serum creatinine to cystatin C ratio and subclinical atherosclerosis in patients with type 2 diabetes. BMJ Open Diabetes Res Care. 2022;10:e002910 (Jun 23). Doi: 10.1136/bmjdrc-2022-002910

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.