SURPASS-4 post hoc analysis reports slower kidney function decline with tirzepatide

A post hoc analysis of the SURPASS-4 trial found that tirzepatide, the active ingredient in Mounjaro and Zepbound, was linked to slower kidney function decline than insulin glargine in adults with type 2 diabetes and high cardiovascular risk ^[1][2]. The analysis is not a new trial. It reexamined data already collected from a study that was designed to look at blood sugar control, not kidney outcomes, so the findings are considered a signal rather than confirmed evidence ^[1].

The study included 1,995 adults with type 2 diabetes and established cardiovascular disease or high cardiovascular risk, who had been randomly assigned to either tirzepatide or insulin glargine and followed for a median of 85 weeks ^[2]. At the start, participants had an average kidney filtration rate, called eGFR, of 81.3 mL/min per 1.73 m2 ^[2]. Over the study period, eGFR declined by 1.4 mL/min per 1.73 m2 per year in people on tirzepatide, compared with 3.6 mL/min per 1.73 m2 per year in people on insulin glargine, a difference of 2.2 mL/min per 1.73 m2 per year ^[1][2].

The gap was even larger in people who already had reduced kidney function at the start, with eGFR below 60 mL/min per 1.73 m2. In that group, the difference in decline rate between the two drugs was 3.7 mL/min per 1.73 m2 per year ^[2]. Researchers also tracked urine albumin, a marker of kidney damage measured as the urine albumin-to-creatinine ratio (UACR). UACR rose by 36.9 percent in the insulin glargine group but did not rise in the tirzepatide group, actually dropping by 6.8 percent, a between-group difference of 31.9 percentage points ^[2].

The study also tracked a combined kidney endpoint: a drop in eGFR of at least 40 percent from baseline, kidney failure, death from kidney failure, or new significant albuminuria. This composite outcome occurred less often in people on tirzepatide, with a hazard ratio of 0.58, meaning the risk was 42 percent lower compared with insulin glargine ^[2]. An accompanying commentary published alongside the analysis in The Lancet Diabetes & Endocrinology described the kidney findings as “intriguing and promising” ^[2]. The trial was funded by Eli Lilly, the maker of tirzepatide ^[2].

Why it matters for patients

People with type 2 diabetes face elevated risk of chronic kidney disease over time, and finding treatments that slow that process matters for long-term health, not just blood sugar numbers. This analysis suggests tirzepatide may have a kidney benefit beyond its known effects on blood sugar, weight, and blood pressure ^[1]. But because this was a post hoc analysis of an open-label trial that was not designed to test kidney outcomes as its primary goal, and because the study compared tirzepatide only against insulin glargine, not a placebo or other kidney-focused drug, the results cannot yet establish that tirzepatide directly protects the kidneys ^[1]. Patients already taking tirzepatide products, or considering them, should understand that kidney effects were a secondary finding from data collected for a different purpose, and that more targeted research would be needed to confirm what the mechanism might be and how meaningful it is for individual patients over the long term.

What happens next

The sources reviewed here do not describe a dedicated, prospective trial designed specifically to test kidney outcomes with tirzepatide. It is not yet known from these sources whether or when such a trial might be conducted or reported.