Type 2 Diabetes ICYMI

Key clinical point: Addition of low-dose (0.25 mg/day) vs. standard-dose (0.5 mg/day) lobeglitazone to metformin plus dipeptidyl peptidase 4 inhibitor (DPP4i) therapy led to noninferior glucose lowering effects and fewer adverse outcomes in patients with type 2 diabetes mellitus (T2D).

Major finding: At week 24, the mean glycated hemoglobin level in the low-dose vs. standard-dose lobeglitazone group was 6.87% ± 0.54% vs. 6.68% ±0 .46%, respectively, with a between-group difference of 0.18% (95% Cl 0.017%-0.345%) showing noninferiority of the low-dose to standard-dose treatment. Treatment-emergent adverse events were more frequent in the standard-dose vs. low-dose group.

Study details: This was a phase 4 study including 134 patients with T2D inadequately controlled on metformin plus DPP4i therapy who were randomly assigned to receive low-dose (n = 67) or standard-dose (n = 67) lobeglitazone.

Disclosures: This study was supported by a research grant from Chong Kun Dang Pharmaceutical

Corporation, Seoul, Republic of Korea.

Source: Ryang S et al. A double-blind, Randomized controlled trial on glucose-lowering EFfects and safety of adding 0.25 or 0.5 mg lobeglitazone in type 2 diabetes patients with INadequate control on metformin and dipeptidyl peptidase-4 inhibitor therapy: REFIND study. Diabetes Obes Metab. 2022 (May 17). Doi: 10.1111/dom.14766.

Key clinical point: Addition of low-dose (0.25 mg/day) vs. standard-dose (0.5 mg/day) lobeglitazone to metformin plus dipeptidyl peptidase 4 inhibitor (DPP4i) therapy led to noninferior glucose lowering effects and fewer adverse outcomes in patients with type 2 diabetes mellitus (T2D).

Major finding: At week 24, the mean glycated hemoglobin level in the low-dose vs. standard-dose lobeglitazone group was 6.87% ± 0.54% vs. 6.68% ±0 .46%, respectively, with a between-group difference of 0.18% (95% Cl 0.017%-0.345%) showing noninferiority of the low-dose to standard-dose treatment. Treatment-emergent adverse events were more frequent in the standard-dose vs. low-dose group.

Study details: This was a phase 4 study including 134 patients with T2D inadequately controlled on metformin plus DPP4i therapy who were randomly assigned to receive low-dose (n = 67) or standard-dose (n = 67) lobeglitazone.

Disclosures: This study was supported by a research grant from Chong Kun Dang Pharmaceutical

Corporation, Seoul, Republic of Korea.

Source: Ryang S et al. A double-blind, Randomized controlled trial on glucose-lowering EFfects and safety of adding 0.25 or 0.5 mg lobeglitazone in type 2 diabetes patients with INadequate control on metformin and dipeptidyl peptidase-4 inhibitor therapy: REFIND study. Diabetes Obes Metab. 2022 (May 17). Doi: 10.1111/dom.14766.

Key clinical point: Addition of low-dose (0.25 mg/day) vs. standard-dose (0.5 mg/day) lobeglitazone to metformin plus dipeptidyl peptidase 4 inhibitor (DPP4i) therapy led to noninferior glucose lowering effects and fewer adverse outcomes in patients with type 2 diabetes mellitus (T2D).

Major finding: At week 24, the mean glycated hemoglobin level in the low-dose vs. standard-dose lobeglitazone group was 6.87% ± 0.54% vs. 6.68% ±0 .46%, respectively, with a between-group difference of 0.18% (95% Cl 0.017%-0.345%) showing noninferiority of the low-dose to standard-dose treatment. Treatment-emergent adverse events were more frequent in the standard-dose vs. low-dose group.

Study details: This was a phase 4 study including 134 patients with T2D inadequately controlled on metformin plus DPP4i therapy who were randomly assigned to receive low-dose (n = 67) or standard-dose (n = 67) lobeglitazone.

Disclosures: This study was supported by a research grant from Chong Kun Dang Pharmaceutical

Corporation, Seoul, Republic of Korea.

Source: Ryang S et al. A double-blind, Randomized controlled trial on glucose-lowering EFfects and safety of adding 0.25 or 0.5 mg lobeglitazone in type 2 diabetes patients with INadequate control on metformin and dipeptidyl peptidase-4 inhibitor therapy: REFIND study. Diabetes Obes Metab. 2022 (May 17). Doi: 10.1111/dom.14766.

Key clinical point: Obesity appeared to be a protective factor for the development of diabetic macular edema (DME) and vision-threatening diabetic retinopathy (VTDR) in patients with type 2 diabetes mellitus (T2D), whereas the waist-to-height ratio appeared to be a significant risk factor.

Major finding: Obesity was associated with a lower risk for DME (adjusted odds ratio [aOR] 0.40; P = .041) and VTDR (aOR 0.37; P = .023), whereas a higher waist-to-height ratio was associated with a higher risk for DME (aOR 3.04; P = .041) and VTDR (aOR 2.74; P = .048), with all associations being more significant in women.

Study details: Findings are from an ongoing prospective study that included 2305 patients with T2D.

Disclosures: This study was supported by the National Natural Science Foundation of China and Guangzhou Science & Technology Plan of Guangdong Pearl River Talents Program. No competing interests were declared.

Source: Li W et al. Association of different kinds of obesity with diabetic retinopathy in patients with type 2 diabetes. BMJ Open. 2023;12:e056332 (May 19). Doi: 10.1136/bmjopen-2021-056332

Key clinical point: Obesity appeared to be a protective factor for the development of diabetic macular edema (DME) and vision-threatening diabetic retinopathy (VTDR) in patients with type 2 diabetes mellitus (T2D), whereas the waist-to-height ratio appeared to be a significant risk factor.

Major finding: Obesity was associated with a lower risk for DME (adjusted odds ratio [aOR] 0.40; P = .041) and VTDR (aOR 0.37; P = .023), whereas a higher waist-to-height ratio was associated with a higher risk for DME (aOR 3.04; P = .041) and VTDR (aOR 2.74; P = .048), with all associations being more significant in women.

Study details: Findings are from an ongoing prospective study that included 2305 patients with T2D.

Disclosures: This study was supported by the National Natural Science Foundation of China and Guangzhou Science & Technology Plan of Guangdong Pearl River Talents Program. No competing interests were declared.

Source: Li W et al. Association of different kinds of obesity with diabetic retinopathy in patients with type 2 diabetes. BMJ Open. 2023;12:e056332 (May 19). Doi: 10.1136/bmjopen-2021-056332

Key clinical point: Obesity appeared to be a protective factor for the development of diabetic macular edema (DME) and vision-threatening diabetic retinopathy (VTDR) in patients with type 2 diabetes mellitus (T2D), whereas the waist-to-height ratio appeared to be a significant risk factor.

Major finding: Obesity was associated with a lower risk for DME (adjusted odds ratio [aOR] 0.40; P = .041) and VTDR (aOR 0.37; P = .023), whereas a higher waist-to-height ratio was associated with a higher risk for DME (aOR 3.04; P = .041) and VTDR (aOR 2.74; P = .048), with all associations being more significant in women.

Study details: Findings are from an ongoing prospective study that included 2305 patients with T2D.

Disclosures: This study was supported by the National Natural Science Foundation of China and Guangzhou Science & Technology Plan of Guangdong Pearl River Talents Program. No competing interests were declared.

Source: Li W et al. Association of different kinds of obesity with diabetic retinopathy in patients with type 2 diabetes. BMJ Open. 2023;12:e056332 (May 19). Doi: 10.1136/bmjopen-2021-056332

Key clinical point: Tirzepatide. at doses of  10 or 15 mg, vs. 2 mg semaglutide was associated with a significantly greater reduction in glycated hemoglobin (A1c) levels and body weight in patients with type 2 diabetes (T2D). Both drugs had a similar overall safety profile.

Major finding: At week 40, 10 and 15 mg tirzepatide vs. 2 mg semaglutide led to a significantly greater reduction in A1c levels (estimated treatment difference [ETD] −0.36%; P = .008, and ETD −0.4%; P = .003, respectively) and body weight (ETD −3.15 and −5.15 kg, respectively; both P < .001).

Study details: This was an adjusted indirect treatment comparison study that included patients with T2D from the SURPASS-2 (n = 1879) and SUSTAIN FORTE (n = 961) trials who were randomly assigned to receive tirzepatide or injectable semaglutide.

Disclosures: This study was funded by Eli Lilly and Company. Two authors declared being advisory board members or receiving speaking or consulting honoraria or research support from various sources, including Eli Lilly. The other authors are employees and shareholders of Eli Lilly.

Source: Vadher K et al. Efficacy of tirzepatide 5, 10 and 15 mg versus semaglutide 2 mg in patients with type 2 diabetes: An adjusted indirect treatment comparison. Diabetes Obes Metab. 2022 (May 19). Doi: 10.1111/dom.14775

Key clinical point: Tirzepatide. at doses of  10 or 15 mg, vs. 2 mg semaglutide was associated with a significantly greater reduction in glycated hemoglobin (A1c) levels and body weight in patients with type 2 diabetes (T2D). Both drugs had a similar overall safety profile.

Major finding: At week 40, 10 and 15 mg tirzepatide vs. 2 mg semaglutide led to a significantly greater reduction in A1c levels (estimated treatment difference [ETD] −0.36%; P = .008, and ETD −0.4%; P = .003, respectively) and body weight (ETD −3.15 and −5.15 kg, respectively; both P < .001).

Study details: This was an adjusted indirect treatment comparison study that included patients with T2D from the SURPASS-2 (n = 1879) and SUSTAIN FORTE (n = 961) trials who were randomly assigned to receive tirzepatide or injectable semaglutide.

Disclosures: This study was funded by Eli Lilly and Company. Two authors declared being advisory board members or receiving speaking or consulting honoraria or research support from various sources, including Eli Lilly. The other authors are employees and shareholders of Eli Lilly.

Source: Vadher K et al. Efficacy of tirzepatide 5, 10 and 15 mg versus semaglutide 2 mg in patients with type 2 diabetes: An adjusted indirect treatment comparison. Diabetes Obes Metab. 2022 (May 19). Doi: 10.1111/dom.14775

Key clinical point: Tirzepatide. at doses of  10 or 15 mg, vs. 2 mg semaglutide was associated with a significantly greater reduction in glycated hemoglobin (A1c) levels and body weight in patients with type 2 diabetes (T2D). Both drugs had a similar overall safety profile.

Major finding: At week 40, 10 and 15 mg tirzepatide vs. 2 mg semaglutide led to a significantly greater reduction in A1c levels (estimated treatment difference [ETD] −0.36%; P = .008, and ETD −0.4%; P = .003, respectively) and body weight (ETD −3.15 and −5.15 kg, respectively; both P < .001).

Study details: This was an adjusted indirect treatment comparison study that included patients with T2D from the SURPASS-2 (n = 1879) and SUSTAIN FORTE (n = 961) trials who were randomly assigned to receive tirzepatide or injectable semaglutide.

Disclosures: This study was funded by Eli Lilly and Company. Two authors declared being advisory board members or receiving speaking or consulting honoraria or research support from various sources, including Eli Lilly. The other authors are employees and shareholders of Eli Lilly.

Source: Vadher K et al. Efficacy of tirzepatide 5, 10 and 15 mg versus semaglutide 2 mg in patients with type 2 diabetes: An adjusted indirect treatment comparison. Diabetes Obes Metab. 2022 (May 19). Doi: 10.1111/dom.14775

Key clinical point: In patients with type 2 diabetes (T2D), once-weekly tirzepatide demonstrated dose-dependent superiority on glycemic efficacy vs. placebo, long-acting glucagon-like peptide-1 receptor agonist (GLP-1 RA), and basal insulin, without increasing the chances of hypoglycemia.

Major finding: Tirzepatide, at does of 5, 10, and 15 mg, was more effective than placebo in reducing glycated hemoglobin levels, with mean differences (95% CI) being −17.71 (−21.66 to −13.75), −20.20 (−22.90 to −17.51), and −22.35 (−26.09 to −18.62) mmol/mol, respectively. Similar findings were recorded for tirzepatide vs. GLP-1 RA or basal insulin. The incidence of hypoglycemia was not significantly different between the treatment groups.

Study details: The data come from a meta-analysis of seven randomized controlled trials including 6609 patients with T2D.

Disclosures: The study received no specific funding. Some authors declared receiving research grants, consulting fees, research support, or honoraria from, or serving as consultants or advisory board members for various sources.

Source: Karagiannis T et al. Management of type 2 diabetes with the dual GIP/GLP-1 receptor agonist tirzepatide: A systematic review and meta-analysis. Diabetologia. 2022 (May 17). Doi: 10.1007/s00125-022-05715-4

Key clinical point: In patients with type 2 diabetes (T2D), once-weekly tirzepatide demonstrated dose-dependent superiority on glycemic efficacy vs. placebo, long-acting glucagon-like peptide-1 receptor agonist (GLP-1 RA), and basal insulin, without increasing the chances of hypoglycemia.

Major finding: Tirzepatide, at does of 5, 10, and 15 mg, was more effective than placebo in reducing glycated hemoglobin levels, with mean differences (95% CI) being −17.71 (−21.66 to −13.75), −20.20 (−22.90 to −17.51), and −22.35 (−26.09 to −18.62) mmol/mol, respectively. Similar findings were recorded for tirzepatide vs. GLP-1 RA or basal insulin. The incidence of hypoglycemia was not significantly different between the treatment groups.

Study details: The data come from a meta-analysis of seven randomized controlled trials including 6609 patients with T2D.

Disclosures: The study received no specific funding. Some authors declared receiving research grants, consulting fees, research support, or honoraria from, or serving as consultants or advisory board members for various sources.

Source: Karagiannis T et al. Management of type 2 diabetes with the dual GIP/GLP-1 receptor agonist tirzepatide: A systematic review and meta-analysis. Diabetologia. 2022 (May 17). Doi: 10.1007/s00125-022-05715-4

Key clinical point: In patients with type 2 diabetes (T2D), once-weekly tirzepatide demonstrated dose-dependent superiority on glycemic efficacy vs. placebo, long-acting glucagon-like peptide-1 receptor agonist (GLP-1 RA), and basal insulin, without increasing the chances of hypoglycemia.

Major finding: Tirzepatide, at does of 5, 10, and 15 mg, was more effective than placebo in reducing glycated hemoglobin levels, with mean differences (95% CI) being −17.71 (−21.66 to −13.75), −20.20 (−22.90 to −17.51), and −22.35 (−26.09 to −18.62) mmol/mol, respectively. Similar findings were recorded for tirzepatide vs. GLP-1 RA or basal insulin. The incidence of hypoglycemia was not significantly different between the treatment groups.

Study details: The data come from a meta-analysis of seven randomized controlled trials including 6609 patients with T2D.

Disclosures: The study received no specific funding. Some authors declared receiving research grants, consulting fees, research support, or honoraria from, or serving as consultants or advisory board members for various sources.

Source: Karagiannis T et al. Management of type 2 diabetes with the dual GIP/GLP-1 receptor agonist tirzepatide: A systematic review and meta-analysis. Diabetologia. 2022 (May 17). Doi: 10.1007/s00125-022-05715-4

Key clinical point: The antepartum 75g-oral glucose tolerance test (75g-OGTT) can identify nulliparous pregnant women who are at risk of developing type 2 diabetes mellitus (T2D), even if they tested negative for gestational diabetes (GD).

Major finding: In women without GD, the fasting (adjusted hazard ratio [aHR] 2.82; 95% CI 2.18-3.64), 1-hour (aHR 1.26; 95% CI 1.15-1.37), and 2-hour (aHR 1.14; 95% CI 1.04-1.25) 75g-OGTT values were significantly associated with a future risk of developing T2D, with a model combining all three OGTT values and clinical characteristics being able to detect 43.7% (95% CI 43.2%-44.2%) of women who developed T2D at 5 years after the index pregnancy.

Study details: The data come from a retrospective study of 41,507 nulliparous pregnant women who tested negative for GD using a 75g-OGTT.

Disclosures: This study was funded by the Canadian Institute of Health Research. The authors report no conflicts of interest.

Source: Hiersch L et al. The prognostic value of the oral glucose tolerance test for future type-2 diabetes in nulliparous pregnant women testing negative for gestational diabetes. Diabetes Metab. 2022 (Jun 2). Doi: 10.1016/j.diabet.2022.101364

Key clinical point: The antepartum 75g-oral glucose tolerance test (75g-OGTT) can identify nulliparous pregnant women who are at risk of developing type 2 diabetes mellitus (T2D), even if they tested negative for gestational diabetes (GD).

Major finding: In women without GD, the fasting (adjusted hazard ratio [aHR] 2.82; 95% CI 2.18-3.64), 1-hour (aHR 1.26; 95% CI 1.15-1.37), and 2-hour (aHR 1.14; 95% CI 1.04-1.25) 75g-OGTT values were significantly associated with a future risk of developing T2D, with a model combining all three OGTT values and clinical characteristics being able to detect 43.7% (95% CI 43.2%-44.2%) of women who developed T2D at 5 years after the index pregnancy.

Study details: The data come from a retrospective study of 41,507 nulliparous pregnant women who tested negative for GD using a 75g-OGTT.

Disclosures: This study was funded by the Canadian Institute of Health Research. The authors report no conflicts of interest.

Source: Hiersch L et al. The prognostic value of the oral glucose tolerance test for future type-2 diabetes in nulliparous pregnant women testing negative for gestational diabetes. Diabetes Metab. 2022 (Jun 2). Doi: 10.1016/j.diabet.2022.101364

Key clinical point: The antepartum 75g-oral glucose tolerance test (75g-OGTT) can identify nulliparous pregnant women who are at risk of developing type 2 diabetes mellitus (T2D), even if they tested negative for gestational diabetes (GD).

Major finding: In women without GD, the fasting (adjusted hazard ratio [aHR] 2.82; 95% CI 2.18-3.64), 1-hour (aHR 1.26; 95% CI 1.15-1.37), and 2-hour (aHR 1.14; 95% CI 1.04-1.25) 75g-OGTT values were significantly associated with a future risk of developing T2D, with a model combining all three OGTT values and clinical characteristics being able to detect 43.7% (95% CI 43.2%-44.2%) of women who developed T2D at 5 years after the index pregnancy.

Study details: The data come from a retrospective study of 41,507 nulliparous pregnant women who tested negative for GD using a 75g-OGTT.

Disclosures: This study was funded by the Canadian Institute of Health Research. The authors report no conflicts of interest.

Source: Hiersch L et al. The prognostic value of the oral glucose tolerance test for future type-2 diabetes in nulliparous pregnant women testing negative for gestational diabetes. Diabetes Metab. 2022 (Jun 2). Doi: 10.1016/j.diabet.2022.101364

Key clinical point: Combination of metformin plus a low hypoglycemic risk antidiabetic drug provides better glycemic control than metformin monotherapy without increasing the risk for hypoglycemia in patients with untreated type 2 diabetes mellitus (T2D).

Major finding: Combination therapy vs. metformin monotherapy significantly reduced glycated hemoglobin (A1c) levels (mean difference [MD] −0.48%; P < .001) and fasting plasma glucose levels (MD −0.92 mmol/L; P < .001) and led to a higher proportion of patients achieving  an A1c level of <7% (odds ratio 2.21; P < .00001), without any significant increase in hypoglycemic events.

Study details: Findings are from a meta-analysis of 14 randomized controlled trials including 5316 patients with untreated T2D who were randomly assigned to receive combination therapy or metformin monotherapy.

Disclosures: This work was supported by Ministry of Science and Technology and Chang Gung Memorial Hospital, Taiwan. The authors declared no conflicts of interest.

Source: Hung WT et al. Metformin plus a low hypoglycemic risk antidiabetic drug vs. metformin monotherapy for untreated type 2 diabetes mellitus: A meta-analysis of randomized controlled trials. Diabetes Res Clin Pract. 2022;189:10937 (Jun 1). Doi: 10.1016/j.diabres.2022.109937

Key clinical point: Combination of metformin plus a low hypoglycemic risk antidiabetic drug provides better glycemic control than metformin monotherapy without increasing the risk for hypoglycemia in patients with untreated type 2 diabetes mellitus (T2D).

Major finding: Combination therapy vs. metformin monotherapy significantly reduced glycated hemoglobin (A1c) levels (mean difference [MD] −0.48%; P < .001) and fasting plasma glucose levels (MD −0.92 mmol/L; P < .001) and led to a higher proportion of patients achieving  an A1c level of <7% (odds ratio 2.21; P < .00001), without any significant increase in hypoglycemic events.

Study details: Findings are from a meta-analysis of 14 randomized controlled trials including 5316 patients with untreated T2D who were randomly assigned to receive combination therapy or metformin monotherapy.

Disclosures: This work was supported by Ministry of Science and Technology and Chang Gung Memorial Hospital, Taiwan. The authors declared no conflicts of interest.

Source: Hung WT et al. Metformin plus a low hypoglycemic risk antidiabetic drug vs. metformin monotherapy for untreated type 2 diabetes mellitus: A meta-analysis of randomized controlled trials. Diabetes Res Clin Pract. 2022;189:10937 (Jun 1). Doi: 10.1016/j.diabres.2022.109937

Key clinical point: Combination of metformin plus a low hypoglycemic risk antidiabetic drug provides better glycemic control than metformin monotherapy without increasing the risk for hypoglycemia in patients with untreated type 2 diabetes mellitus (T2D).

Major finding: Combination therapy vs. metformin monotherapy significantly reduced glycated hemoglobin (A1c) levels (mean difference [MD] −0.48%; P < .001) and fasting plasma glucose levels (MD −0.92 mmol/L; P < .001) and led to a higher proportion of patients achieving  an A1c level of <7% (odds ratio 2.21; P < .00001), without any significant increase in hypoglycemic events.

Study details: Findings are from a meta-analysis of 14 randomized controlled trials including 5316 patients with untreated T2D who were randomly assigned to receive combination therapy or metformin monotherapy.

Disclosures: This work was supported by Ministry of Science and Technology and Chang Gung Memorial Hospital, Taiwan. The authors declared no conflicts of interest.

Source: Hung WT et al. Metformin plus a low hypoglycemic risk antidiabetic drug vs. metformin monotherapy for untreated type 2 diabetes mellitus: A meta-analysis of randomized controlled trials. Diabetes Res Clin Pract. 2022;189:10937 (Jun 1). Doi: 10.1016/j.diabres.2022.109937

Key clinical point: Patients with type 2 diabetes (T2D) who initiated first-line sodium-glucose cotransporter-2 inhibitors (SGLT-2i) vs. metformin showed a similar risk for hospitalization for myocardial infarction (MI)/stroke or all-cause mortality, a lower risk for hospitalization for heart failure (HHF) or all-cause mortality, and a similar safety profile, except for an increased risk for genital infections.

Major finding: Patients initiating the first-line treatment with SGLT-2i vs. metformin had a similar risk for MI/stroke/mortality (hazard ratio[HR] 0.96; 95% CI 0.77-1.19), a lower risk for HHF/mortality (HR 0.80; 95% CI 0.66-0.97), and a similar safety profile, except for an increased risk for genital infections (HR 2.19; 95% CI 1.91-2.51).

Study details: This population-based cohort study included 8613 patients with T2D initiating SGLT-2i and 17,226 matched patients initiating metformin.

Disclosures: This study was funded by the Brigham and Women's Hospital and Harvard Medical School. RJ Glynn, E Patorno, and S Schneeweiss declared receiving research grants or consulting fees, serving on advisory boards, or holding stock or stock options for various sources.

Source: Shin H et al. Cardiovascular outcomes in patients initiating first-line treatment of type 2 diabetes with sodium–glucose cotransporter-2 inhibitors versus metformin: A cohort study. Ann Intern Med. 2022 (May 24). Doi: 10.7326/M21-4012

Key clinical point: Patients with type 2 diabetes (T2D) who initiated first-line sodium-glucose cotransporter-2 inhibitors (SGLT-2i) vs. metformin showed a similar risk for hospitalization for myocardial infarction (MI)/stroke or all-cause mortality, a lower risk for hospitalization for heart failure (HHF) or all-cause mortality, and a similar safety profile, except for an increased risk for genital infections.

Major finding: Patients initiating the first-line treatment with SGLT-2i vs. metformin had a similar risk for MI/stroke/mortality (hazard ratio[HR] 0.96; 95% CI 0.77-1.19), a lower risk for HHF/mortality (HR 0.80; 95% CI 0.66-0.97), and a similar safety profile, except for an increased risk for genital infections (HR 2.19; 95% CI 1.91-2.51).

Study details: This population-based cohort study included 8613 patients with T2D initiating SGLT-2i and 17,226 matched patients initiating metformin.

Disclosures: This study was funded by the Brigham and Women's Hospital and Harvard Medical School. RJ Glynn, E Patorno, and S Schneeweiss declared receiving research grants or consulting fees, serving on advisory boards, or holding stock or stock options for various sources.

Source: Shin H et al. Cardiovascular outcomes in patients initiating first-line treatment of type 2 diabetes with sodium–glucose cotransporter-2 inhibitors versus metformin: A cohort study. Ann Intern Med. 2022 (May 24). Doi: 10.7326/M21-4012

Key clinical point: Patients with type 2 diabetes (T2D) who initiated first-line sodium-glucose cotransporter-2 inhibitors (SGLT-2i) vs. metformin showed a similar risk for hospitalization for myocardial infarction (MI)/stroke or all-cause mortality, a lower risk for hospitalization for heart failure (HHF) or all-cause mortality, and a similar safety profile, except for an increased risk for genital infections.

Major finding: Patients initiating the first-line treatment with SGLT-2i vs. metformin had a similar risk for MI/stroke/mortality (hazard ratio[HR] 0.96; 95% CI 0.77-1.19), a lower risk for HHF/mortality (HR 0.80; 95% CI 0.66-0.97), and a similar safety profile, except for an increased risk for genital infections (HR 2.19; 95% CI 1.91-2.51).

Study details: This population-based cohort study included 8613 patients with T2D initiating SGLT-2i and 17,226 matched patients initiating metformin.

Disclosures: This study was funded by the Brigham and Women's Hospital and Harvard Medical School. RJ Glynn, E Patorno, and S Schneeweiss declared receiving research grants or consulting fees, serving on advisory boards, or holding stock or stock options for various sources.

Source: Shin H et al. Cardiovascular outcomes in patients initiating first-line treatment of type 2 diabetes with sodium–glucose cotransporter-2 inhibitors versus metformin: A cohort study. Ann Intern Med. 2022 (May 24). Doi: 10.7326/M21-4012

Key clinical point: Once-weekly dulaglutide was superior to placebo in improving glycemic control through 26 weeks in youths with inadequately controlled type 2 diabetes (T2D) who were being treated with or without metformin or basal insulin.

Major finding: At 26 weeks, 0.75 mg and 1.5 mg dulaglutide vs. placebo led to a significant reduction in mean glycated hemoglobin (A1c) level (estimated treatment difference −1.2% and −1.5%, respectively), in addition to a significant increase in the proportion of patients achieving an A1c level of <7.0% (all P < .001) and a consistent safety profile.

Study details: The data come from the AWARD-PEDS trial including 154 patients with T2D treated with lifestyle modification alone or metformin with or without basal insulin and who were randomly assigned to receive once-weekly dulaglutide or placebo for 26 weeks.

Disclosures: This study was funded by Eli Lilly and Company. Some authors declared receiving grants or contracts or serving as consultants or on safety and data monitoring boards for various sources, including Eli Lilly. D Cox declared being an employee of and holding stocks or stock options in Eli Lilly.

Source: Arslanian SA et al. Once-weekly dulaglutide for the treatment of youths with type 2 diabetes. N Engl J Med. 2022 (Jun 4). Doi: 10.1056/NEJMoa2204601

Key clinical point: Once-weekly dulaglutide was superior to placebo in improving glycemic control through 26 weeks in youths with inadequately controlled type 2 diabetes (T2D) who were being treated with or without metformin or basal insulin.

Major finding: At 26 weeks, 0.75 mg and 1.5 mg dulaglutide vs. placebo led to a significant reduction in mean glycated hemoglobin (A1c) level (estimated treatment difference −1.2% and −1.5%, respectively), in addition to a significant increase in the proportion of patients achieving an A1c level of <7.0% (all P < .001) and a consistent safety profile.

Study details: The data come from the AWARD-PEDS trial including 154 patients with T2D treated with lifestyle modification alone or metformin with or without basal insulin and who were randomly assigned to receive once-weekly dulaglutide or placebo for 26 weeks.

Disclosures: This study was funded by Eli Lilly and Company. Some authors declared receiving grants or contracts or serving as consultants or on safety and data monitoring boards for various sources, including Eli Lilly. D Cox declared being an employee of and holding stocks or stock options in Eli Lilly.

Source: Arslanian SA et al. Once-weekly dulaglutide for the treatment of youths with type 2 diabetes. N Engl J Med. 2022 (Jun 4). Doi: 10.1056/NEJMoa2204601

Key clinical point: Once-weekly dulaglutide was superior to placebo in improving glycemic control through 26 weeks in youths with inadequately controlled type 2 diabetes (T2D) who were being treated with or without metformin or basal insulin.

Major finding: At 26 weeks, 0.75 mg and 1.5 mg dulaglutide vs. placebo led to a significant reduction in mean glycated hemoglobin (A1c) level (estimated treatment difference −1.2% and −1.5%, respectively), in addition to a significant increase in the proportion of patients achieving an A1c level of <7.0% (all P < .001) and a consistent safety profile.

Study details: The data come from the AWARD-PEDS trial including 154 patients with T2D treated with lifestyle modification alone or metformin with or without basal insulin and who were randomly assigned to receive once-weekly dulaglutide or placebo for 26 weeks.

Disclosures: This study was funded by Eli Lilly and Company. Some authors declared receiving grants or contracts or serving as consultants or on safety and data monitoring boards for various sources, including Eli Lilly. D Cox declared being an employee of and holding stocks or stock options in Eli Lilly.

Source: Arslanian SA et al. Once-weekly dulaglutide for the treatment of youths with type 2 diabetes. N Engl J Med. 2022 (Jun 4). Doi: 10.1056/NEJMoa2204601

Patients with type 2 diabetes who received empagliflozin, a sodium glucose cotransporter-2 (SGLT2) inhibitor, were almost 40% less likely to have a kidney stone than patients who received placebo during a median 1.5 years of treatment.

These findings are from an analysis of pooled data from phase 1-4 clinical trials of empagliflozin for blood glucose control in 15,081 patients with type 2 diabetes.  

Priyadarshini Balasubramanian, MD, presented the study as a poster at the annual meeting of the Endocrine Society; the study also was published online in the Journal of Clinical Endocrinology & Metabolism.

The researchers acknowledge this was a retrospective, post-hoc analysis and that urolithiasis – a stone in the urinary tract, which includes nephrolithiasis, a kidney stone – was an adverse event, not a primary or secondary outcome.

Also, the stone composition, which might help explain how the drug may affect stone formation, is unknown.

Therefore, “dedicated randomized prospective clinical trials are needed to confirm these initial observations in patients both with and without type 2 diabetes,” said Dr. Balasubramanian, a clinical fellow in the section of endocrinology & metabolism, department of internal medicine at Yale University, New Haven, Conn.

However, “if this association is proven, empagliflozin may be used to decrease the risk of kidney stones at least in those with type 2 diabetes, but maybe also in those without diabetes,” Dr. Balasubramanian said in an interview.

Further trials are also needed to determine if this is a class effect, which is likely, she speculated, and to unravel the potential mechanism.

This is important because of the prevalence of kidney stones, which affect up to 15% of the general population and 15%-20% of patients with diabetes, she explained.
 

‘Provocative’ earlier findings

The current study was prompted by a recent observational study by Kasper B. Kristensen, MD, PhD, and colleagues.

Because SGLT2 inhibitors increase urinary glucose excretion through reduced renal reabsorption of glucose leading to osmotic diuresis and increased urinary flow, they hypothesized that these therapies “may reduce the risk of upper urinary tract stones (nephrolithiasis) by reducing the concentration of lithogenic substances in urine.” 

Using data from Danish Health registries, they matched 12,325 individuals newly prescribed an SGLT2 inhibitor 1:1 with patients newly prescribed a glucagonlike peptide-1 (GLP1) agonist, another new class of drugs for treating type 2 diabetes.

They found a hazard ratio of 0.51 (95% confidence interval, 0.37-0.71) for incident nephrolithiasis and a hazard ratio of 0.68 (95% CI, 0.48-0.97) for recurrent nephrolithiasis for patients taking SGLT2 inhibitors versus GLP-1 agonists.

These findings are “striking,” according to Dr. Balasubramanian and colleagues. However, “these data, while provocative, were entirely retrospective and therefore possibly prone to bias,” they add.
 

Pooled data from 20 trials

The current study analyzed data from 20 randomized controlled trials of glycemic control in type 2 diabetes, in which 10,177 patients had received empagliflozin 10 mg or 25 mg and 4,904 patients had received placebo.

Most patients (46.5%) had participated in the EMPA-REG OUTCOMES trial, which also had the longest follow-up (2.6 years).

The researchers identified patients with a new stone from the urinary tract (including the kidney, ureter, and urethra). Patients had received either the study drug for a median of 543 days or placebo for a median of 549 days.

During treatment, 104 of 10,177 patients in the pooled empagliflozin groups and 79 of 4,904 patients in the pooled placebo groups developed a stone in the urinary tract.

This was equivalent to 0.63 new urinary-tract stones per 100 patient-years in the pooled empagliflozin groups versus 1.01 new urinary-tract stones per 100 patient-years in the pooled placebo groups.

The incidence rate ratio was 0.64 (95% CI, 0.48-0.86), in favor of empagliflozin.

When the analysis was restricted to new kidney stones, the results were similar: 75 of 10,177 patients in the pooled empagliflozin groups and 57 of 4,904 patients in the pooled placebo groups developed a kidney stone.

This was equivalent to 0.45 new kidney stones per 100 patient-years in the pooled empagliflozin groups versus 0.72 new kidney stones per 100 patient-years in the pooled placebo groups.

The IRR was 0.65 (95% CI, 0.46-0.92), in favor of empagliflozin.
 

Upcoming small RCT in adults without diabetes

Invited to comment on the new study, Dr. Kristensen said: “The reduced risk of SGLT2 inhibitors towards nephrolithiasis is now reported in at least two studies with different methodology, different populations, and different exposure and outcome definitions.”

“I agree that randomized clinical trials designed specifically to confirm these findings appear warranted,” added Dr. Kristensen, from the Institute of Public Health, Clinical Pharmacology, Pharmacy, and Environmental Medicine, University of Southern Denmark in Odense.

There is a need for studies in patients with and without diabetes, he added, especially ones that focus on prevention of nephrolithiasis in patients with kidney stone disease.

A new trial should shed further light on this.

Results are expected by the end of 2022 for SWEETSTONE (Impact of the SGLT2 Inhibitor Empagliflozin on Urinary Supersaturations in Kidney Stone Formers), a randomized, double-blind crossover exploratory study in 46 patients without diabetes.

This should provide preliminary data to “establish the relevance for larger trials assessing the prophylactic potential of empagliflozin in kidney stone disease,” according to an article on the trial protocol recently published in BMJ.

The trials included in the pooled dataset were funded by Boehringer Ingelheim or the Boehringer Ingelheim and Eli Lilly Diabetes Alliance. Dr. Balasubramanian has reported no relevant financial relationships.

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

Patients with type 2 diabetes who received empagliflozin, a sodium glucose cotransporter-2 (SGLT2) inhibitor, were almost 40% less likely to have a kidney stone than patients who received placebo during a median 1.5 years of treatment.

These findings are from an analysis of pooled data from phase 1-4 clinical trials of empagliflozin for blood glucose control in 15,081 patients with type 2 diabetes.  

Priyadarshini Balasubramanian, MD, presented the study as a poster at the annual meeting of the Endocrine Society; the study also was published online in the Journal of Clinical Endocrinology & Metabolism.

The researchers acknowledge this was a retrospective, post-hoc analysis and that urolithiasis – a stone in the urinary tract, which includes nephrolithiasis, a kidney stone – was an adverse event, not a primary or secondary outcome.

Also, the stone composition, which might help explain how the drug may affect stone formation, is unknown.

Therefore, “dedicated randomized prospective clinical trials are needed to confirm these initial observations in patients both with and without type 2 diabetes,” said Dr. Balasubramanian, a clinical fellow in the section of endocrinology & metabolism, department of internal medicine at Yale University, New Haven, Conn.

However, “if this association is proven, empagliflozin may be used to decrease the risk of kidney stones at least in those with type 2 diabetes, but maybe also in those without diabetes,” Dr. Balasubramanian said in an interview.

Further trials are also needed to determine if this is a class effect, which is likely, she speculated, and to unravel the potential mechanism.

This is important because of the prevalence of kidney stones, which affect up to 15% of the general population and 15%-20% of patients with diabetes, she explained.
 

‘Provocative’ earlier findings

The current study was prompted by a recent observational study by Kasper B. Kristensen, MD, PhD, and colleagues.

Because SGLT2 inhibitors increase urinary glucose excretion through reduced renal reabsorption of glucose leading to osmotic diuresis and increased urinary flow, they hypothesized that these therapies “may reduce the risk of upper urinary tract stones (nephrolithiasis) by reducing the concentration of lithogenic substances in urine.” 

Using data from Danish Health registries, they matched 12,325 individuals newly prescribed an SGLT2 inhibitor 1:1 with patients newly prescribed a glucagonlike peptide-1 (GLP1) agonist, another new class of drugs for treating type 2 diabetes.

They found a hazard ratio of 0.51 (95% confidence interval, 0.37-0.71) for incident nephrolithiasis and a hazard ratio of 0.68 (95% CI, 0.48-0.97) for recurrent nephrolithiasis for patients taking SGLT2 inhibitors versus GLP-1 agonists.

These findings are “striking,” according to Dr. Balasubramanian and colleagues. However, “these data, while provocative, were entirely retrospective and therefore possibly prone to bias,” they add.
 

Pooled data from 20 trials

The current study analyzed data from 20 randomized controlled trials of glycemic control in type 2 diabetes, in which 10,177 patients had received empagliflozin 10 mg or 25 mg and 4,904 patients had received placebo.

Most patients (46.5%) had participated in the EMPA-REG OUTCOMES trial, which also had the longest follow-up (2.6 years).

The researchers identified patients with a new stone from the urinary tract (including the kidney, ureter, and urethra). Patients had received either the study drug for a median of 543 days or placebo for a median of 549 days.

During treatment, 104 of 10,177 patients in the pooled empagliflozin groups and 79 of 4,904 patients in the pooled placebo groups developed a stone in the urinary tract.

This was equivalent to 0.63 new urinary-tract stones per 100 patient-years in the pooled empagliflozin groups versus 1.01 new urinary-tract stones per 100 patient-years in the pooled placebo groups.

The incidence rate ratio was 0.64 (95% CI, 0.48-0.86), in favor of empagliflozin.

When the analysis was restricted to new kidney stones, the results were similar: 75 of 10,177 patients in the pooled empagliflozin groups and 57 of 4,904 patients in the pooled placebo groups developed a kidney stone.

This was equivalent to 0.45 new kidney stones per 100 patient-years in the pooled empagliflozin groups versus 0.72 new kidney stones per 100 patient-years in the pooled placebo groups.

The IRR was 0.65 (95% CI, 0.46-0.92), in favor of empagliflozin.
 

Upcoming small RCT in adults without diabetes

Invited to comment on the new study, Dr. Kristensen said: “The reduced risk of SGLT2 inhibitors towards nephrolithiasis is now reported in at least two studies with different methodology, different populations, and different exposure and outcome definitions.”

“I agree that randomized clinical trials designed specifically to confirm these findings appear warranted,” added Dr. Kristensen, from the Institute of Public Health, Clinical Pharmacology, Pharmacy, and Environmental Medicine, University of Southern Denmark in Odense.

There is a need for studies in patients with and without diabetes, he added, especially ones that focus on prevention of nephrolithiasis in patients with kidney stone disease.

A new trial should shed further light on this.

Results are expected by the end of 2022 for SWEETSTONE (Impact of the SGLT2 Inhibitor Empagliflozin on Urinary Supersaturations in Kidney Stone Formers), a randomized, double-blind crossover exploratory study in 46 patients without diabetes.

This should provide preliminary data to “establish the relevance for larger trials assessing the prophylactic potential of empagliflozin in kidney stone disease,” according to an article on the trial protocol recently published in BMJ.

The trials included in the pooled dataset were funded by Boehringer Ingelheim or the Boehringer Ingelheim and Eli Lilly Diabetes Alliance. Dr. Balasubramanian has reported no relevant financial relationships.

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

Patients with type 2 diabetes who received empagliflozin, a sodium glucose cotransporter-2 (SGLT2) inhibitor, were almost 40% less likely to have a kidney stone than patients who received placebo during a median 1.5 years of treatment.

These findings are from an analysis of pooled data from phase 1-4 clinical trials of empagliflozin for blood glucose control in 15,081 patients with type 2 diabetes.  

Priyadarshini Balasubramanian, MD, presented the study as a poster at the annual meeting of the Endocrine Society; the study also was published online in the Journal of Clinical Endocrinology & Metabolism.

The researchers acknowledge this was a retrospective, post-hoc analysis and that urolithiasis – a stone in the urinary tract, which includes nephrolithiasis, a kidney stone – was an adverse event, not a primary or secondary outcome.

Also, the stone composition, which might help explain how the drug may affect stone formation, is unknown.

Therefore, “dedicated randomized prospective clinical trials are needed to confirm these initial observations in patients both with and without type 2 diabetes,” said Dr. Balasubramanian, a clinical fellow in the section of endocrinology & metabolism, department of internal medicine at Yale University, New Haven, Conn.

However, “if this association is proven, empagliflozin may be used to decrease the risk of kidney stones at least in those with type 2 diabetes, but maybe also in those without diabetes,” Dr. Balasubramanian said in an interview.

Further trials are also needed to determine if this is a class effect, which is likely, she speculated, and to unravel the potential mechanism.

This is important because of the prevalence of kidney stones, which affect up to 15% of the general population and 15%-20% of patients with diabetes, she explained.
 

‘Provocative’ earlier findings

The current study was prompted by a recent observational study by Kasper B. Kristensen, MD, PhD, and colleagues.

Because SGLT2 inhibitors increase urinary glucose excretion through reduced renal reabsorption of glucose leading to osmotic diuresis and increased urinary flow, they hypothesized that these therapies “may reduce the risk of upper urinary tract stones (nephrolithiasis) by reducing the concentration of lithogenic substances in urine.” 

Using data from Danish Health registries, they matched 12,325 individuals newly prescribed an SGLT2 inhibitor 1:1 with patients newly prescribed a glucagonlike peptide-1 (GLP1) agonist, another new class of drugs for treating type 2 diabetes.

They found a hazard ratio of 0.51 (95% confidence interval, 0.37-0.71) for incident nephrolithiasis and a hazard ratio of 0.68 (95% CI, 0.48-0.97) for recurrent nephrolithiasis for patients taking SGLT2 inhibitors versus GLP-1 agonists.

These findings are “striking,” according to Dr. Balasubramanian and colleagues. However, “these data, while provocative, were entirely retrospective and therefore possibly prone to bias,” they add.
 

Pooled data from 20 trials

The current study analyzed data from 20 randomized controlled trials of glycemic control in type 2 diabetes, in which 10,177 patients had received empagliflozin 10 mg or 25 mg and 4,904 patients had received placebo.

Most patients (46.5%) had participated in the EMPA-REG OUTCOMES trial, which also had the longest follow-up (2.6 years).

The researchers identified patients with a new stone from the urinary tract (including the kidney, ureter, and urethra). Patients had received either the study drug for a median of 543 days or placebo for a median of 549 days.

During treatment, 104 of 10,177 patients in the pooled empagliflozin groups and 79 of 4,904 patients in the pooled placebo groups developed a stone in the urinary tract.

This was equivalent to 0.63 new urinary-tract stones per 100 patient-years in the pooled empagliflozin groups versus 1.01 new urinary-tract stones per 100 patient-years in the pooled placebo groups.

The incidence rate ratio was 0.64 (95% CI, 0.48-0.86), in favor of empagliflozin.

When the analysis was restricted to new kidney stones, the results were similar: 75 of 10,177 patients in the pooled empagliflozin groups and 57 of 4,904 patients in the pooled placebo groups developed a kidney stone.

This was equivalent to 0.45 new kidney stones per 100 patient-years in the pooled empagliflozin groups versus 0.72 new kidney stones per 100 patient-years in the pooled placebo groups.

The IRR was 0.65 (95% CI, 0.46-0.92), in favor of empagliflozin.
 

Upcoming small RCT in adults without diabetes

Invited to comment on the new study, Dr. Kristensen said: “The reduced risk of SGLT2 inhibitors towards nephrolithiasis is now reported in at least two studies with different methodology, different populations, and different exposure and outcome definitions.”

“I agree that randomized clinical trials designed specifically to confirm these findings appear warranted,” added Dr. Kristensen, from the Institute of Public Health, Clinical Pharmacology, Pharmacy, and Environmental Medicine, University of Southern Denmark in Odense.

There is a need for studies in patients with and without diabetes, he added, especially ones that focus on prevention of nephrolithiasis in patients with kidney stone disease.

A new trial should shed further light on this.

Results are expected by the end of 2022 for SWEETSTONE (Impact of the SGLT2 Inhibitor Empagliflozin on Urinary Supersaturations in Kidney Stone Formers), a randomized, double-blind crossover exploratory study in 46 patients without diabetes.

This should provide preliminary data to “establish the relevance for larger trials assessing the prophylactic potential of empagliflozin in kidney stone disease,” according to an article on the trial protocol recently published in BMJ.

The trials included in the pooled dataset were funded by Boehringer Ingelheim or the Boehringer Ingelheim and Eli Lilly Diabetes Alliance. Dr. Balasubramanian has reported no relevant financial relationships.

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

For most of us, the “best” time of day to work out is simple: When we can.

Maybe that’s before or after work. Or when the gym offers free daycare. Or when our favorite instructor teaches our favorite class.

That’s why we call it a “routine.” And if the results are the same, it’s hard to imagine changing it up.

But what if the results aren’t the same?

pojoslaw/Thinkstock

They may not be, according to a new study from a research team at Skidmore College in Saratoga Springs, N.Y. The results of a 12-week exercise program were different for morning versus evening workouts.

Women who worked out in the morning lost more fat, while those who trained in the evening gained more upper-body strength and power. As for men, the performance improvements were similar no matter when they exercised. But those who did so in the evening had a significant drop in blood pressure, among other benefits.

The study is part of a growing body of research showing different results for different times of day among different populations. As it turns out, when you exercise can ultimately have a big effect, not just on strength and fat loss, but also heart health, mood, and quality of sleep.
 

An accidental discovery

The original goal of the Skidmore study was to test a unique fitness program with a group of healthy, fit, and extremely active adults in early middle age.

The program includes four workouts a week, each with a different focus: strength, steady-pace endurance, high-intensity intervals, and flexibility (traditional stretching combined with yoga and Pilates exercises).

But because the group was so large – 27 women and 20 men completed the 3-month program – they had to split them into morning and evening workout groups.

It wasn’t until researchers looked at the results that they saw the differences between morning and evening exercise, says lead author Paul Arciero, PhD.

Dr. Arciero stressed that participants in every group got leaner and stronger. But the women who worked out in the morning got much bigger reductions in body fat and body-fat percentage than the evening group. Meanwhile, women in the evening group got much bigger gains in upper-body strength, power, and muscular endurance than their morning counterparts.

Among the men, the evening group had significantly larger improvements in blood pressure, cholesterol levels, and the percentage of fat they burned for energy, along with a bigger drop in feelings of fatigue.
 

Strategic timing for powerful results

Some of these findings are consistent with previous research. For example, a study published in 2021 showed that the ability to exert high effort and express strength and power peaks in the late afternoon, about the same time that your core body temperature is at its highest point.

On the other hand, you’ll probably perform better in the morning when the activity requires a lot of skill and coordination or depends on strategic decision-making.

The findings apply to both men and women.

Performance aside, exercise timing might offer strong health benefits for men with type 2 diabetes, or at high risk for it.

A study showed that men who exercised between 3 p.m. and 6 p.m. saw dramatic improvements in blood sugar management and insulin sensitivity, compared to a group that worked out between 8 a.m. and 10 a.m.

They also lost more fat during the 12-week program, even though they were doing the exact same workouts.
 

Train consistently, sleep well

When you exercise can affect your sleep quality in many ways, said neuroscientist Jennifer Heisz, PhD, of McMaster University, Hamilton, Ont.

First, she said, “exercise helps you fall asleep faster and sleep deeper at night.” (The only exception is if you exercise so intensely or so close to bedtime that your heart rate is still elevated.)

Second, “exercising at a consistent time every day helps regulate the body’s circadian rhythms.” It doesn’t matter if the exercise is in the morning, evening, or anywhere in between. As long as it’s predictable, it will help you fall asleep and wake up at the same times.

Outdoor exercise is even better, she said. The sun is the most powerful regulator of the circadian clock and works in tandem with physical activity.

Third, exercising at specific times can help you overcome jet lag or adjust to an earlier or later shift at work.

“Exercising at 7 a.m. or between 1 and 4 p.m. helps your circadian clock to ‘fall back’ in time, making it easier to wake up earlier,” Dr. Heisz said. If you need to train your body to wake up later in the morning, try working out between 7 p.m. and 10 p.m.
 

All exercise is good, but the right timing can make it even better

“The best time to exercise is when you can fit it in,” Dr. Arciero said. “You’ve got to choose the time that fits your lifestyle best.”

But context matters, he noted.

“For someone needing to achieve an improvement in their risk for cardiometabolic disease,” his study shows an advantage to working out later in the day, especially for men. If you’re more focused on building upper-body strength and power, you’ll probably get better results from training in the afternoon or evening.

And for fat loss, the Skidmore study shows better results for women who did morning workouts.

And if you’re still not sure? Try sleeping on it – preferably after your workout.

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

For most of us, the “best” time of day to work out is simple: When we can.

Maybe that’s before or after work. Or when the gym offers free daycare. Or when our favorite instructor teaches our favorite class.

That’s why we call it a “routine.” And if the results are the same, it’s hard to imagine changing it up.

But what if the results aren’t the same?

pojoslaw/Thinkstock

They may not be, according to a new study from a research team at Skidmore College in Saratoga Springs, N.Y. The results of a 12-week exercise program were different for morning versus evening workouts.

Women who worked out in the morning lost more fat, while those who trained in the evening gained more upper-body strength and power. As for men, the performance improvements were similar no matter when they exercised. But those who did so in the evening had a significant drop in blood pressure, among other benefits.

The study is part of a growing body of research showing different results for different times of day among different populations. As it turns out, when you exercise can ultimately have a big effect, not just on strength and fat loss, but also heart health, mood, and quality of sleep.
 

An accidental discovery

The original goal of the Skidmore study was to test a unique fitness program with a group of healthy, fit, and extremely active adults in early middle age.

The program includes four workouts a week, each with a different focus: strength, steady-pace endurance, high-intensity intervals, and flexibility (traditional stretching combined with yoga and Pilates exercises).

But because the group was so large – 27 women and 20 men completed the 3-month program – they had to split them into morning and evening workout groups.

It wasn’t until researchers looked at the results that they saw the differences between morning and evening exercise, says lead author Paul Arciero, PhD.

Dr. Arciero stressed that participants in every group got leaner and stronger. But the women who worked out in the morning got much bigger reductions in body fat and body-fat percentage than the evening group. Meanwhile, women in the evening group got much bigger gains in upper-body strength, power, and muscular endurance than their morning counterparts.

Among the men, the evening group had significantly larger improvements in blood pressure, cholesterol levels, and the percentage of fat they burned for energy, along with a bigger drop in feelings of fatigue.
 

Strategic timing for powerful results

Some of these findings are consistent with previous research. For example, a study published in 2021 showed that the ability to exert high effort and express strength and power peaks in the late afternoon, about the same time that your core body temperature is at its highest point.

On the other hand, you’ll probably perform better in the morning when the activity requires a lot of skill and coordination or depends on strategic decision-making.

The findings apply to both men and women.

Performance aside, exercise timing might offer strong health benefits for men with type 2 diabetes, or at high risk for it.

A study showed that men who exercised between 3 p.m. and 6 p.m. saw dramatic improvements in blood sugar management and insulin sensitivity, compared to a group that worked out between 8 a.m. and 10 a.m.

They also lost more fat during the 12-week program, even though they were doing the exact same workouts.
 

Train consistently, sleep well

When you exercise can affect your sleep quality in many ways, said neuroscientist Jennifer Heisz, PhD, of McMaster University, Hamilton, Ont.

First, she said, “exercise helps you fall asleep faster and sleep deeper at night.” (The only exception is if you exercise so intensely or so close to bedtime that your heart rate is still elevated.)

Second, “exercising at a consistent time every day helps regulate the body’s circadian rhythms.” It doesn’t matter if the exercise is in the morning, evening, or anywhere in between. As long as it’s predictable, it will help you fall asleep and wake up at the same times.

Outdoor exercise is even better, she said. The sun is the most powerful regulator of the circadian clock and works in tandem with physical activity.

Third, exercising at specific times can help you overcome jet lag or adjust to an earlier or later shift at work.

“Exercising at 7 a.m. or between 1 and 4 p.m. helps your circadian clock to ‘fall back’ in time, making it easier to wake up earlier,” Dr. Heisz said. If you need to train your body to wake up later in the morning, try working out between 7 p.m. and 10 p.m.
 

All exercise is good, but the right timing can make it even better

“The best time to exercise is when you can fit it in,” Dr. Arciero said. “You’ve got to choose the time that fits your lifestyle best.”

But context matters, he noted.

“For someone needing to achieve an improvement in their risk for cardiometabolic disease,” his study shows an advantage to working out later in the day, especially for men. If you’re more focused on building upper-body strength and power, you’ll probably get better results from training in the afternoon or evening.

And for fat loss, the Skidmore study shows better results for women who did morning workouts.

And if you’re still not sure? Try sleeping on it – preferably after your workout.

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

For most of us, the “best” time of day to work out is simple: When we can.

Maybe that’s before or after work. Or when the gym offers free daycare. Or when our favorite instructor teaches our favorite class.

That’s why we call it a “routine.” And if the results are the same, it’s hard to imagine changing it up.

But what if the results aren’t the same?

pojoslaw/Thinkstock

They may not be, according to a new study from a research team at Skidmore College in Saratoga Springs, N.Y. The results of a 12-week exercise program were different for morning versus evening workouts.

Women who worked out in the morning lost more fat, while those who trained in the evening gained more upper-body strength and power. As for men, the performance improvements were similar no matter when they exercised. But those who did so in the evening had a significant drop in blood pressure, among other benefits.

The study is part of a growing body of research showing different results for different times of day among different populations. As it turns out, when you exercise can ultimately have a big effect, not just on strength and fat loss, but also heart health, mood, and quality of sleep.
 

An accidental discovery

The original goal of the Skidmore study was to test a unique fitness program with a group of healthy, fit, and extremely active adults in early middle age.

The program includes four workouts a week, each with a different focus: strength, steady-pace endurance, high-intensity intervals, and flexibility (traditional stretching combined with yoga and Pilates exercises).

But because the group was so large – 27 women and 20 men completed the 3-month program – they had to split them into morning and evening workout groups.

It wasn’t until researchers looked at the results that they saw the differences between morning and evening exercise, says lead author Paul Arciero, PhD.

Dr. Arciero stressed that participants in every group got leaner and stronger. But the women who worked out in the morning got much bigger reductions in body fat and body-fat percentage than the evening group. Meanwhile, women in the evening group got much bigger gains in upper-body strength, power, and muscular endurance than their morning counterparts.

Among the men, the evening group had significantly larger improvements in blood pressure, cholesterol levels, and the percentage of fat they burned for energy, along with a bigger drop in feelings of fatigue.
 

Strategic timing for powerful results

Some of these findings are consistent with previous research. For example, a study published in 2021 showed that the ability to exert high effort and express strength and power peaks in the late afternoon, about the same time that your core body temperature is at its highest point.

On the other hand, you’ll probably perform better in the morning when the activity requires a lot of skill and coordination or depends on strategic decision-making.

The findings apply to both men and women.

Performance aside, exercise timing might offer strong health benefits for men with type 2 diabetes, or at high risk for it.

A study showed that men who exercised between 3 p.m. and 6 p.m. saw dramatic improvements in blood sugar management and insulin sensitivity, compared to a group that worked out between 8 a.m. and 10 a.m.

They also lost more fat during the 12-week program, even though they were doing the exact same workouts.
 

Train consistently, sleep well

When you exercise can affect your sleep quality in many ways, said neuroscientist Jennifer Heisz, PhD, of McMaster University, Hamilton, Ont.

First, she said, “exercise helps you fall asleep faster and sleep deeper at night.” (The only exception is if you exercise so intensely or so close to bedtime that your heart rate is still elevated.)

Second, “exercising at a consistent time every day helps regulate the body’s circadian rhythms.” It doesn’t matter if the exercise is in the morning, evening, or anywhere in between. As long as it’s predictable, it will help you fall asleep and wake up at the same times.

Outdoor exercise is even better, she said. The sun is the most powerful regulator of the circadian clock and works in tandem with physical activity.

Third, exercising at specific times can help you overcome jet lag or adjust to an earlier or later shift at work.

“Exercising at 7 a.m. or between 1 and 4 p.m. helps your circadian clock to ‘fall back’ in time, making it easier to wake up earlier,” Dr. Heisz said. If you need to train your body to wake up later in the morning, try working out between 7 p.m. and 10 p.m.
 

All exercise is good, but the right timing can make it even better

“The best time to exercise is when you can fit it in,” Dr. Arciero said. “You’ve got to choose the time that fits your lifestyle best.”

But context matters, he noted.

“For someone needing to achieve an improvement in their risk for cardiometabolic disease,” his study shows an advantage to working out later in the day, especially for men. If you’re more focused on building upper-body strength and power, you’ll probably get better results from training in the afternoon or evening.

And for fat loss, the Skidmore study shows better results for women who did morning workouts.

And if you’re still not sure? Try sleeping on it – preferably after your workout.

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