Summary: In this post hoc analysis of the SUSTAIN 6 trial, 1139 adults with type 2 diabetes and no diabetic kidney disease (DKD) at baseline were grouped by predicted DKD risk. Once-weekly semaglutide was associated with a lower odds of developing DKD versus placebo (total population odds ratio 0.56, 95% CI 0.42 to 0.74, p < 0.0001), with an odds ratio of 0.51 (95% CI 0.38 to 0.69) and a number needed to treat of 7 in the high-risk subgroup. As an exploratory post hoc finding, this is hypothesis-generating rather than confirmatory.
PICO Summary
| Element | Detail |
|---|---|
| Population | 1139 adults with type 2 diabetes and no DKD at baseline, drawn from the randomised, double-blind, placebo-controlled SUSTAIN 6 trial (multinational); 952 of 1139 were classified as high DKD risk by a validated prediction model. Overall, 28.7% developed DKD during follow-up. |
| Intervention | Once-weekly subcutaneous semaglutide 0.5 mg or 1.0 mg. |
| Comparison | Matching placebo, double-blind. |
| Outcome | New-onset DKD (UACR ≥30 mg/g and/or eGFR <60 mL/min/1.73 m²). Total population: odds ratio 0.56 (95% CI 0.42 to 0.74; p < 0.0001). High DKD risk subgroup: odds ratio 0.51 (95% CI 0.38 to 0.69; p < 0.0001), number needed to treat 7. Semaglutide also significantly delayed DKD onset; the benefit was largely driven by reductions in urinary albumin-to-creatinine ratio (UACR). As a post hoc analysis, no formal multiplicity adjustment applied and findings are associational within a randomised dataset. |
Semaglutide and primary prevention of diabetic kidney disease
SUSTAIN 6 post hoc · type 2 diabetes · ~2 years
In this exploratory post hoc analysis, once-weekly semaglutide was associated with roughly half the odds of new-onset DKD versus placebo, with an NNT of 7 in the high-risk subgroup. Hypothesis-generating, not confirmatory.
Expert Commentary
This post hoc analysis of SUSTAIN 6 adds to a consistent body of renal signals for semaglutide, but its standing should be read with care. The verdict is encouraging yet preliminary: a halving of the odds of new-onset DKD in the high-risk subgroup, with a number needed to treat of 7, is a clinically meaningful effect size if it holds, and the gradient across risk strata lends internal coherence. The dominant limitation is the design itself. These outcomes were not pre-specified primary endpoints of SUSTAIN 6; DKD risk was assigned retrospectively using a prediction model, no multiplicity adjustment was reported, and a soft composite anchored partly on UACR can be moved by haemodynamic and glycaemic effects that need not reflect durable structural protection. Industry involvement is also relevant, as several authors were employed by the manufacturer, which warrants the usual caution around analytical choices in a post hoc setting. Can I use this with my patients? Not yet as a standalone reason to prescribe, but it reinforces semaglutide as a reasonable choice in a person with type 2 diabetes who already has a cardiometabolic indication and elevated kidney risk, where renal benefit is a welcome secondary consideration. A prospective trial powered for incident DKD, with hard renal endpoints, would be needed to convert this promising association into practice-changing evidence.
References
Wang J, Yang J, Jiang W, Liu W, Shen Z, Gao Z, Chang B. Effect of semaglutide on primary prevention of diabetic kidney disease in people with type 2 diabetes: A post hoc analysis of the SUSTAIN 6 randomized controlled trial. Diabetes Obes Metab. 2024;26(11):5157-5166. doi:10.1111/dom.15860