Effects of Semaglutide on Albuminuria and Kidney Function in People With Overweight or Obesity With or Without Type 2 Diabetes: Exploratory Analysis From the STEP 1, 2, and 3 Trials

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 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.</p

Semaglutide 2.4 mg for the Treatment of Obesity: Key Elements of the STEP 1–5 Randomized Trials

Objective:The obesity epidemic is a public health concern, warranting further research intopharmacological treatments for weight management as an adjunct to lifestyle interventions. TheSemaglutide Treatment Effect in People with obesity (STEP) program aims to investigate the effect ofsemaglutide versus placebo on weight loss (WL), safety, and tolerability in adults with obesity oroverweight.Methods:Across five phase 3 trials (NCT03548935– weight management, NCT03552757– weightmanagement (WM) in type 2 diabetes, NCT03611582– WM with intensive behavioral therapy,NCT03548987– sustained WM, NCT03693430– long-term WM), ~5000 participants are randomizedto receive semaglutide 2.4 mg once weekly subcutaneously versus placebo. Results are available in2020/2021. For all trials, the primary endpoint is change from baseline to end of treatment in bodyweightResults:Participants have a mean age of 46.2–55.3 years, mostly female (mean 74.1–81.0%), a mean body mass index of 35.7–38.5 kg/m2and mean waist circumference of 113.0–115.7 cm.Conclusions:The STEP program evaluates the efficacy and safety of semaglutide 2.4 mg subcutaneously once-weekly in a broad population. The trials will provide insights on weight management in people with obesity with and without type 2 diabetes, long-term follow-up, and mitigating development of comorbidities and complications.</p