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

Abstract

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.

Graphical abstract

Figure 1

A: Percent change in UACR from baseline to week 68. B: Distribution of patients by UACR status at baseline and week 68. Proportions are based on the number of patients in each UACR status category at the visit over the total number of patients with a UACR observation at the visit. The left-hand bar in each pair refers to baseline and the right-hand bar to week 68. C: Patients with changes in UACR status from baseline to week 68. Proportions are based on the number of patients with an improvement in UACR status from baseline to week 68 over the total number of patients with a UACR observation at both time points; a large proportion of patients were not included in this analysis because of missing data at baseline (n = 7 for semaglutide 1.0 mg, n = 8 for semaglutide 2.4 mg, and n = 3 for placebo) or week 68 (n = 57 for semaglutide 1.0 mg, n = 55 for semaglutide 2.4 mg, and n = 67 for placebo). Improvement is regression of baseline macroalbuminuria to microalbuminuria/normal or microalbuminuria to normal at week 68. Worsening is progression of baseline normal albuminuria to microalbuminuria/macroalbuminuria or microalbuminuria to macroalbuminuria at week 68. ETD, estimated treatment difference.

Figure 2

Change in UACR by subgroup analyses. Data are for the trial product estimand (assesses treatment effect if all patients adhered to treatment without rescue intervention) unless otherwise stated. RI, renal impairment; SBP, systolic blood pressure; SGLT2i, SGLT2 inhibitor.