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

INTRODUCTION

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.

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 1.0mg (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.

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 1.0mg, 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], P<0.0001 semaglutide 1.0mg; −32.9% [−41.6, −23.0], P=0.003 semaglutide 2.4mg). UACR status improved in greater proportions of patients with semaglutide 1.0 and 2.4mg 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 2.4mg and placebo in eGFR trajectories at week 68.

CONCLUSION

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.