Effects of tirzepatide versus insulin glargine on kidney outcomes in type 2 diabetes in the SURPASS-4 trial: post-hoc analysis of an open-label, randomised, phase 3 trial
In a post-hoc analysis of the SURPASS-4 trial, tirzepatide slowed eGFR decline, reduced albuminuria, and lowered the composite kidney endpoint compared with insulin glargine in people with type 2 diabetes at high cardiovascular risk.
Background
Tirzepatide, a dual GIP/GLP-1 receptor agonist, improved glucose, weight, and blood pressure more than insulin glargine in SURPASS-4. This analysis compared their effects on kidney function and outcomes.
Study design
Post-hoc analysis of SURPASS-4 (NCT03730662), an open-label phase 3 trial at 187 sites across 14 countries. 2002 adults with type 2 diabetes (on oral agents, with established cardiovascular disease or high CV risk) were randomized to once-weekly tirzepatide (5, 10, or 15 mg) or titrated daily insulin glargine (median treatment ~85 weeks). The analysis compared eGFR-decline rate, UACR, and a composite kidney endpoint (≥40% eGFR decline, end-stage kidney disease, kidney-failure death, or new macroalbuminuria).
Key findings
The annual eGFR decline was slower with tirzepatide than insulin glargine (−1.4 vs −3.6 ml/min/1.73 m²/year; between-group difference 2.2), with greater benefit in participants with baseline eGFR <60. UACR rose with insulin glargine (+36.9%) but not with tirzepatide (−6.8%; between-group difference −31.9%). Tirzepatide significantly lowered the composite kidney endpoint (hazard ratio 0.58, 95% CI 0.43–0.80).
Clinical implications
Tirzepatide produced clinically meaningful kidney protection — slower eGFR decline and reduced albuminuria — versus insulin glargine in high-risk type 2 diabetes. As a post-hoc analysis with insulin (not placebo) as comparator, dedicated prospective kidney-outcome trials are needed to confirm these benefits.
Category
Research
Source
The Lancet Diabetes & Endocrinology
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