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. 2023 Apr 1;46(4):801-810.
doi: 10.2337/dc22-1889.

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

Hiddo J L Heerspink  1 , Ellen Apperloo  1 , Melanie Davies  2   3   4 , Dror Dicker  5   6 , Kristian Kandler  7 , Julio Rosenstock  8 , Rasmus Sørrig  9 , Jack Lawson  9 , Niels Zeuthen  10 , David Cherney  11
Affiliations

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

Hiddo J L Heerspink et al. Diabetes Care. .

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.

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Conflict of interest statement

Duality of Interest. H.J.L.H. is a consultant for AbbVie, AstraZeneca, Bayer, Boehringer Ingelheim, Chinook Therapeutics, CSL Pharma, Gilead Sciences, Inc., Janssen, Merck, Mitsubishi Tanabe, Mundipharma, Novo Nordisk, and Travere Therapeutics; and has received research support for conducting investigator-initiated clinical trials from AbbVie, AstraZeneca, Boehringer Ingelheim, Janssen, and Novo Nordisk. M.D. received research funding from AstraZeneca, Boehringer Ingelheim, Janssen, Novo Nordisk, and Sanofi-Aventis; served as consultant, advisory board member, and speaker for Boehringer Ingelheim, Eli Lilly, Novo Nordisk, and Sanofi-Aventis; served as advisory board member and speaker for AstraZeneca; is an advisory board member for Gilead Sciences, Inc., Janssen, and Lexicon Pharmaceuticals; and is a speaker for Napp Pharmaceuticals and Takeda Pharmaceuticals International Inc., cofunded by the NIHR Leicester Biomedical Research Centre. D.D. received research funding from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Novo Nordisk, and Sanofi-Aventis; and served as consultant, advisory board member, and speaker for AstraZeneca, Boehringer Ingelheim, Eli Lilly, Merck Sharp & Dohme, Novo Nordisk, and Sanofi-Aventis. K.K. and J.L. are employees of Novo Nordisk A/S. J.R. received scientific advisory board fees, honoraria, consulting fees, and grants/research support from Novo Nordisk, Applied Therapeutics, Boehringer Ingelheim, Eli Lilly, Intarcia Therapeutics, Novo Nordisk, Oramed Pharmaceuticals, and Sanofi; received honoraria or consulting fees from Zealand Pharma; and received grants/research support from Genentech, Novartis, Pfizer, REMD Biotherapeutics, and vTv Therapeutics. R.S. and N.Z. are employees and shareholders of Novo Nordisk A/S. D.C. has received honoraria from AbbVie, AstraZeneca, Bayer, Boehringer Ingelheim-Lilly, Bristol-Myers Squibb, CSL-Behring, Gilead Sciences, Inc., Janssen, Lexicon Pharmaceuticals, Maze Therapeutics, Merck, Mitsubishi Tanabe, Novartis, Novo Nordisk, Otsuka, Prometic Pharma, Sanofi, and Youngene Therapeutics and has received operational funding for clinical trials from AstraZeneca, Boehringer Ingelheim-Lilly, CSL-Behring, Janssen, Merck, Novo Nordisk, and Sanofi. No other potential conflicts of interest relevant to this article were reported.

Figures

None
Graphical abstract
Figure 1
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
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.
See this image and copyright information in PMC

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