Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are well established in clinical practice for the treatment of type 2 diabetes, and are approved and recommended for weight management in overwe...

The first dipeptidyl peptidase 4 (DPP-4) inhibitor sitagliptin was approved in 2006 as treatment for diabetes concurrently with lifestyle changes. A combined product of sitagliptin and glucophage was approved by the U.S. Food and Drug Administration in 2007. The second DPP-4 inhibitor, saxagliptin, was approved in the U.S. It was approved both as monotherapy as well as in combination with metformin, sulfonylurea, or thiazolidinedione. The use of a DPP-4 inhibitor called vildagliptin was approved in Europe and Latin America also as a combination with metformin, sulfonylurea, or thiazolidinedione. Two other DPP-4 inhibitors are also available (linagliptin and alogliptin). In this review, we will elaborate only on the first three drugs (sitagliptin, saxagliptin, and vildagliptin). The different DPP-4 inhibitors are distinctive in their metabolism (saxagliptin and vildagliptin are metabolized in the liver and sitagliptin is not), their excretion, their recommended dosage, and the daily dosage that is required for effective treatment. They are similar, however, when comparing their efficacy regarding lowering HbA1c levels, safety profile, and patient tolerance. The influence of DPP-4 inhibitors on the blood levels of HbA1c as monotherapy or in combination with other oral antidiabetes drugs was tested in multiple trials lasting 12–52 weeks. The results of these important trials were reviewed by Davidson (1) and will be summarized here briefly. Treatment with sitagliptin showed an average decrease in HbA1c levels of 0.65% after 12 weeks of treatment, 0.84% after 18 weeks of treatment, 0.85% after 24 weeks of treatment, 1.0% after 30 weeks of treatment, and 0.67% after 52 weeks of treatment. Treatment with saxagliptin showed an average decrease in HbA1c levels of 0.43–1.17%. Treatment with vildagliptin showed an average decrease in HbA1c levels of 1.4% after 24 weeks as monotherapy in a subgroup of patients with no prior oral treatment and …

OBJECTIVE Most individuals with type 2 diabetes also have obesity, and treatment with some diabetes medications, including insulin, can cause further weight gain. No approved chronic weight management medications have been prospectively investigated in individuals with overweight or obesity and insulin-treated type 2 diabetes. The primary objective of this study was to assess the effect of liraglutide 3.0 mg versus placebo on weight loss in this population. RESEARCH DESIGN AND METHODS Satiety and Clinical Adiposity—Liraglutide Evidence (SCALE) Insulin was a 56-week, randomized, double-blind, placebo-controlled, multinational, multicenter trial in individuals with overweight or obesity and type 2 diabetes treated with basal insulin and ≤2 oral antidiabetic drugs. RESULTS Individuals were randomized to liraglutide 3.0 mg (n = 198) or placebo (n = 198), combined with intensive behavioral therapy (IBT). At 56 weeks, mean weight change was −5.8% for liraglutide 3.0 mg versus −1.5% with placebo (estimated treatment difference −4.3% [95% CI −5.5; −3.2]; P < 0.0001). With liraglutide 3.0 mg, 51.8% of individuals achieved ≥5% weight loss versus 24.0% with placebo (odds ratio 3.41 [95% CI 2.19; 5.31]; P < 0.0001). Liraglutide 3.0 mg was associated with significantly greater reductions in mean HbA_1c and mean daytime glucose values and less need for insulin versus placebo, despite a treat-to-glycemic-target protocol. More hypoglycemic events were observed with placebo than liraglutide 3.0 mg. No new safety or tolerability issues were observed. CONCLUSIONS In individuals with overweight or obesity and insulin-treated type 2 diabetes, liraglutide 3.0 mg as an adjunct to IBT was superior to placebo regarding weight loss and improved glycemic control despite lower doses of basal insulin and without increases in hypoglycemic events.

Summary: We aimed to assess the effectiveness of exercise training programs in adults with severe obesity undergoing bariatric surgery. A systematic search of controlled trials published up to October 2019 that assigned participants to either a preoperative or postoperative exercise training group or a nonexercise group was performed. Meta‐analyses were conducted using random‐effects models. Twenty‐two training programs were assessed (18 performed after bariatric surgery). The effect of preoperative exercise training on postsurgery outcomes was reported in only one study. Compared with the control condition without exercise, postoperative exercise training led to higher weight loss (N = 14, mean difference [95% CI] = −1.8 [−3.2; −0.4] kg,P = 0.01), fat loss (N = 9,P = 0.01), increase in VO₂max (N = 8,P < 0.0001), and increase in muscle strength (N = 9,P < 0.0001). No significant effect was found on lean body mass (N = 11). Preliminary evidence suggests a beneficial effect of postoperative exercise training on bone mineral density (N = 3,P < 0.001) and weight maintenance after the end of the intervention (N = 2,P < 0.001) but no significant effect on quality of life (N = 2), habitual physical activity (N = 2), or cardiometabolic outcomes (N < 4). In conclusion, exercise training performed after bariatric surgery improves physical fitness and leads to a small additional weight and fat loss and may prevent bone loss and weight regain after bariatric surgery.

Summary: This systematic review examined the impact of exercise intervention programs on selected cardiometabolic health indicators in adults with overweight or obesity. Three electronic databases were explored for randomized controlled trials (RCTs) that included adults with overweight or obesity and provided exercise‐training interventions. Effects on blood pressure, insulin resistance (homeostasis model of insulin resistance, HOMA‐IR), and magnetic resonance measures of intrahepatic fat in exercise versus control groups were analyzed using random effects meta‐analyses. Fifty‐four articles matched inclusion criteria. Exercise training reduced systolic and diastolic blood pressure (mean difference, MD = −2.95 mmHg [95% CI −4.22, −1.68], p < 0.00001, I² = 63% and MD = −1.93 mmHg [95% CI −2.73, −1.13], p < 0.00001, I² = 54%, 60 and 58 study arms, respectively). Systolic and diastolic blood pressure decreased also when considering only subjects with hypertension. Exercise training significantly decreased HOMA‐IR (standardized mean difference, SMD = −0.34 [−0.49, −0.18], p < 0.0001, I² = 48%, 37 study arms), with higher effect size in subgroup of patients with type 2 diabetes (SMD = −0.50 [95% CI: −0.83, −0.17], p = 0.003, I² = 39%). Intrahepatic fat decreased significantly after exercise interventions (SMD = −0.59 [95% CI: −0.78, −0.41], p < 0.00001, I² = 0%), with a larger effect size after high‐intensity interval training. In conclusion, exercise training is effective in improving cardiometabolic health in adults with overweight or obesity also when living with comorbitidies.

OBJECTIVE: These post hoc analyses of the Semaglutide Treatment Effect in People with obesity (STEP) 1–3 trials (NCT03548935, NCT03552757, and NCT03611582) explored the effects of semaglutide (up to 2.4 mg) on kidney function.RESEARCH DESIGN AND METHODS: STEP 1–3 included adults with overweight/obesity; STEP 2 patients also had type 2 diabetes. Participants received once-weekly subcutaneous semaglutide 1.0 mg (STEP 2 only), 2.4 mg, or placebo for 68 weeks, plus lifestyle intervention (STEP 1 and 2) or intensive behavioral therapy (STEP 3). Changes in urine albumin-to-creatinine ratio (UACR) and UACR status from baseline to week 68 were assessed for STEP 2. Changes in estimated glomerular filtration rate (eGFR) were assessed from pooled STEP 1–3 data.RESULTS: In STEP 2, 1,205 (99.6% total cohort) patients had UACR data; geometric mean baseline UACR was 13.7, 12.5, and 13.2 mg/g with semaglutide 1.0 mg, 2.4 mg, and placebo, respectively. At week 68, UACR changes were −14.8% and −20.6% with semaglutide 1.0 mg and 2.4 mg, respectively, and +18.3% with placebo (between-group differences [95% CI] vs. placebo: −28.0% [−37.3, −17.3], P < 0.0001 for semaglutide 1.0 mg; −32.9% [−41.6, −23.0], P = 0.003 for semaglutide 2.4 mg). UACR status improved in greater proportions of patients with semaglutide 1.0 mg and 2.4 mg versus placebo (P = 0.0004 and P = 0.0014, respectively). In the pooled STEP 1–3 analyses, 3,379 participants had eGFR data; there was no difference between semaglutide 2.4 mg and placebo in eGFR trajectories at week 68.CONCLUSIONS: Semaglutide improved UACR in adults with overweight/obesity and type 2 diabetes. In participants with normal kidney function, semaglutide did not have an effect on eGFR decline.