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Randomized Controlled Trial
. 2025 Feb 4;40(2):352-359.
doi: 10.1093/ndt/gfae150.

Effect of semaglutide on kidney function across different levels of baseline HbA1c, blood pressure, body weight and albuminuria in SUSTAIN 6 and PIONEER 6

Ellen M Apperloo  1 , David Z I Cherney  2 , Anja Birk Kuhlman  3 , Johannes F E Mann  4   5 , Søren Rasmussen  3 , Peter Rossing  6   7 , Katherine R Tuttle  8 , Blaz Vrhnjak  3 , Hiddo J L Heerspink  1   9
Affiliations
Randomized Controlled Trial

Effect of semaglutide on kidney function across different levels of baseline HbA1c, blood pressure, body weight and albuminuria in SUSTAIN 6 and PIONEER 6

Ellen M Apperloo et al. Nephrol Dial Transplant. .

Abstract

Background: This post hoc analysis explored the effects of semaglutide on estimated glomerular filtration (eGFR) slope by baseline glycemic control, blood pressure (BP), body mass index (BMI) and albuminuria status in people with type 2 diabetes and high cardiovascular risk.

Methods: Pooled SUSTAIN 6 (Trial to Evaluate Cardiovascular and Other Long-Term Outcomes With Semaglutide in Subjects With Type 2 Diabetes) and PIONEER 6 (A Trial Investigating the Cardiovascular Safety of Oral Semaglutide in Subjects With Type 2 Diabetes) data were analyzed for change in eGFR slope by baseline hemoglobin A1c (HbA1c) (<8%/≥8%; <64/≥64 mmol/mol), systolic BP (<140/90/≥140/90 mmHg) and BMI (<30/≥30 kg/m2). SUSTAIN 6 data were analyzed by baseline urinary albumin:creatinine ratio (UACR; <30/30-300/>300 mg/g).

Results: The estimated absolute treatment differences overall in eGFR slope (95% confidence intervals) favored semaglutide versus placebo in the pooled analysis [0.59 (0.29; 0.89) mL/min/1.73 m2/year] and in SUSTAIN 6 [0.60 (0.24; 0.96) mL/min/1.73 m2/year]; the absolute benefit was consistent across all HbA1c, BP, BMI and UACR subgroups (all P-interaction >.5).

Conclusion: A clinically meaningful reduction in risk of chronic kidney disease progression was observed with semaglutide versus placebo regardless of HbA1c, BP, BMI, and UACR levels.

Keywords: cardiovascular risk; diabetes; eGFR decline; semaglutide.

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Conflict of interest statement

E.M.A. reports no conflicts of interest. D.Z.I.C. has received honoraria from Boehringer Ingelheim-Lilly, Merck, AstraZeneca, Sanofi, Mitsubishi-Tanabe, Abbvie, Janssen, Bayer, Prometic, BMS, Maze, Gilead, CSL-Behring, Otsuka, Novartis, Youngene, Lexicon, Inversago, GSK and Novo Nordisk; and has received operational funding for clinical trials from Boehringer Ingelheim-Lilly, Merck, Janssen, Sanofi, AstraZeneca, CSL-Behring and Novo Nordisk. J.F.E.M. reports grants from Novo Nordisk, the European Union and McMaster University Hamilton, Canada; consulting fees from Novo Nordisk, AstraZeneca, Bayer and Boehringer Ingelheim; honoraria from Novo Nordisk, AstraZeneca, Bayer, Fresenius and Novartis; and has participated on a data safety monitoring board or advisory board for AstraZeneca, Bayer, Sanofi and Boehringer Ingelheim as well as a leadership role in the KDIGO group. K.R.T. is supported by NIH research grants R01MD014712, U2CDK114886, UL1TR002319, U54DK083912, U01DK100846, OT2HL161847, UM1AI109568 and CDC project number 75D301-21-P-12254. She has also received investigator-initiated grant support from Travere and Bayer Pharmaceuticals outside of the submitted work. She reports consultancy fees from AstraZeneca, Boehringer Ingelheim, Eli Lilly and Company, Novo Nordisk and Travere. H.J.L.H. is consultant for AstraZeneca, Bayer, Boehringer Ingelheim, CSL-Behring, Eli-Lilly and Company, Gilead, Janssen, Novartis, Novo Nordisk, and Travere Pharmaceuticals. He received research support from Abbvie, AstraZeneca, Boehringer Ingelheim, Janssen and Novo Nordisk. A.B.K., S.R. and B.V. are Novo Nordisk employees. Data included in this manuscript were presented as abstracts to the American Society of Nephrology Annual Meeting in 2022.

Figures

Graphical Abstract
Graphical Abstract
Figure 1:
Figure 1:
Analysis of eGFR slope by baseline HbA1c (A), BP (B), BMI (C) and UACR (D) subgroups (unadjusted*). Estimated treatment differences are shown at 1 year for HbA1c and BP subgroups, and at 1 and 2 years for the UACR subgroups. *Random slope model of repeated eGFR measures analyzed with eGFR value as dependent variable adjusted by baseline value, and time interacting with treatment and subgroup. Intercept and slopes of effect of time are assumed to vary randomly among individuals based on a two-dimensional normal distribution. CI, confidence interval; ETD, estimated treatment difference; geom., geometric; pinteraction, interaction P-value.
Figure 2:
Figure 2:
Analysis of eGFR slope by baseline HbA1c, BP and UACR, stratified by eGFR ≥30–<60 mL/min/1.73 m2 and ≥60 mL/min/1.73 m2 (unadjusted*). Estimated treatment differences are shown at 1 year for all subgroups. *Random slope model of repeated eGFR measures analyzed with eGFR value as dependent variable adjusted by baseline value, and time interacting with treatment and subgroup. Intercept and slopes of effect of time are assumed to vary randomly among individuals based on a two-dimensional normal distribution. CI, confidence interval; ETD, estimated treatment difference; pinteraction, interaction P-value.
Figure 3:
Figure 3:
Analysis of eGFR slope by baseline HbA1c (A), BP (B), BMI (C) and UACR (D) subgroups (adjusted*). Estimated treatment differences are shown at 1 year for HbA1c and BP subgroups, and at 1 and 2 years for the UACR subgroups. *Adjusted for age, sex, diabetes duration, antidiabetes medication, smoking status, previous myocardial infarction/stroke/transient ischemic attack and geographic region. CI, confidence interval; ETD, estimated treatment difference; pinteraction, interaction P-value.
See this image and copyright information in PMC

References

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