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

Heerspink, HJL; Apperloo, E; Davies, M; Dicker, D; Kandler, K; Rosenstock, J; Sørrig, R; Lawson, J; Zeuthen, N; Cherney, D

doi:10.2337/dc22-1889

Obesity

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

Diabetes CarePublished 17 Feb 2023Post hoc exploratory analysis of the STEP 1, 2 and 3 randomised trials

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Authors' 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.

Study context

Population: Adults with overweight/obesity (STEP 1–3); STEP 2 patients also had T2D; plus lifestyle intervention (STEP 1 and 2) or intensive behavioral therapy (STEP 3)STEP 2 with urine albumin-to-creatinine ratio (UACR) data
Participants: 1,205 adults

Comparison: Once-weekly subcutaneous semaglutide 1.0 mg or 2.4 mg vs placebo for 68 weeks
Primary endpoint: Change in UACR and UACR status (STEP 2); change in eGFR (pooled STEP 1-3)
Follow-up: Baseline to week 68

Methodological detailspooled STEP 1-3 analysis for estimated glomerular filtration rate (eGFR)

Pooled STEP 1-3 analysis for eGFR

Primary result

As reported in the abstract

UACR change (STEP 2) · week 68

Semaglutide 1.0 mg

−14.8%

Semaglutide 2.4 mg

−20.6%

Placebo

+18.3%

Each group vs placeboBetween-group difference (95% CI)P value

Semaglutide 1.0 mg

−28.0%(−37.3 to −17.3)

P < 0.0001

Semaglutide 2.4 mg

−32.9%(−41.6 to −23.0)

P = 0.003

Further findings

Baseline UACR (STEP 2) · mean baseline

Semaglutide 1.0 mggeometric mean 13.7 mg/g

Semaglutide 2.4 mggeometric mean 12.5 mg/g

Placebogeometric mean 13.2 mg/g

Improved UACR status (STEP 2) · week 68 · Semaglutide 1.0 mg vs Placebo · greater proportion improved with semaglutide: P = 0.0004
Improved UACR status (STEP 2) · week 68 · Semaglutide 2.4 mg vs Placebo · greater proportion improved with semaglutide: P = 0.0014

eGFR trajectories (pooled STEP 1-3, 3,379 participants) · week 68

No difference between semaglutide 2.4 mg and placebo in eGFR trajectories

Original publication

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. Diabetes Care. Published 17 February 2023. doi:10.2337/dc22-1889

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