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

<p>  </p> <p><strong>INTRODUCTION</strong></p> <p>These post hoc analyses of the STEP 1–3 trials (NCT03548935, NCT03552757, NCT03611582) explored the effects of semaglutide (up to 2.4mg) on kidney function.</p> <p><strong>RESEARCH DESIGN AND METHODS</strong></p> <p>STEP 1–3 included adults with overweight/obesity; STEP 2 patients also had type 2 diabetes. Participants received once-weekly subcutaneous semaglutide 1.0mg (STEP 2 only), 2.4mg, 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.</p> <p><strong>RESULTS</strong></p> <p>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 1.0mg, 2.4mg, and placebo, respectively. At week 68, UACR changes were –14.8% and –20.6% with semaglutide 1.0 and 2.4mg, respectively, and +18.3% with placebo (between-group differences [95% confidence interval] vs. placebo: −28.0% [−37.3, −17.3], <em>P</em><0.0001 semaglutide 1.0mg; −32.9% [−41.6, −23.0], <em>P</em>=0.003 semaglutide 2.4mg). UACR status improved in greater proportions of patients with semaglutide 1.0 and 2.4mg versus placebo (<em>P</em>=0.0004 and <em>P</em>=0.0014, respectively). In the pooled STEP 1–3 analyses, 3,379 participants had eGFR data; there was no difference between semaglutide 2.4mg and placebo in eGFR trajectories at week 68.</p> <p><strong>CONCLUSION</strong></p> <p>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>