Kidney analysis of two tirzepatide trials finds no adverse filtration signal

A post hoc analysis of the SURMOUNT-1 and SURMOUNT-2 trials found that tirzepatide (sold as Mounjaro and Zepbound) reduced urine albumin and did not produce adverse changes in estimated glomerular filtration rate, or eGFR, in adults with overweight or obesity, with or without type 2 diabetes ^[1]. The analysis was published in the Journal of the American Society of Nephrology ^[1].

SURMOUNT-1 enrolled 2,539 people with overweight or obesity but without type 2 diabetes, who were assigned at random to weekly tirzepatide 5, 10, or 15 mg, or placebo ^[1]. SURMOUNT-2 enrolled 938 people with type 2 diabetes, assigned to tirzepatide 10 or 15 mg, or placebo ^[1]. Treatment lasted 72 weeks, followed by a four-week period without the drug ^[1]. At the start, the median urine albumin-to-creatinine ratio, or UACR, was 6.0 mg/g in SURMOUNT-1 and 13.0 mg/g in SURMOUNT-2 ^[1].

By week 72, UACR fell more with tirzepatide than with placebo in both trials. The estimated difference was 8.4% lower in SURMOUNT-1 (95% confidence interval, 14.7 to 1.6) and 31.1% lower in SURMOUNT-2 (95% CI, 40.9 to 19.7) ^[1]. Among participants who started with a UACR of 30 mg/g or higher, the placebo-corrected reductions at week 72 were 42.3% (95% CI, 60.8 to 15.0) in SURMOUNT-1 and 55.2% (95% CI, 68.5 to 36.4) in SURMOUNT-2 ^[1].

On filtration rate, SURMOUNT-1 showed higher eGFR with tirzepatide when it was estimated using cystatin C, with a mean difference versus placebo at week 72 of 3.2 mL/min per 1.73 m2 (95% CI, 2.1 to 4.3), and when estimated using creatinine plus cystatin C, with a difference of 1.9 mL/min per 1.73 m2 (95% CI, 0.9 to 2.9) ^[1]. In SURMOUNT-2, both the tirzepatide and placebo groups increased on those two measures, and there was no difference between the groups ^[1].

Kidney-related safety events were uncommon. Acute kidney injury was reported in 0.3% to 0.6% of the tirzepatide groups versus 0.2% on placebo in SURMOUNT-1, and in 1% of participants on the 10 mg dose versus 0.3% on placebo in SURMOUNT-2 ^[1]. The authors concluded that tirzepatide was associated with reduced albuminuria without adverse changes in eGFR ^[1].

Why it matters for patients

Albumin in the urine is an early sign of kidney stress, and it often appears before filtration rate drops, so a treatment that lowers it without harming filtration is a signal worth watching ^[1]. Many people with obesity or type 2 diabetes are at higher risk of losing kidney function over time, and current kidney-protective drugs have little effect on body weight ^[1].

There are limits to what this analysis can show. It was a post hoc analysis, meaning kidney measures were not the outcomes the two trials were originally built to test ^[1]. Participants generally started with healthy filtration: in SURMOUNT-1 the average was 100 mL/min per 1.73 m2 based on creatinine ^[1]. Results for people who already have meaningfully reduced kidney function have not been reported in this analysis, and it does not establish whether tirzepatide prevents kidney failure, dialysis, or other hard outcomes over the long term.

What happens next

The findings do not by themselves change how tirzepatide is prescribed, and no regulatory action or labeling change tied to this analysis has been announced. The trials are registered as SURMOUNT-1 (NCT04184622) and SURMOUNT-2 (NCT04657003); neither registry listing in this paper describes kidney outcomes as a primary endpoint ^[1]. Whether longer follow-up or studies designed specifically around kidney outcomes will be run has not been disclosed.