Tirzepatide linked to lower albuminuria in post hoc analysis of SURMOUNT trials

A post hoc analysis of the SURMOUNT-1 and SURMOUNT-2 trials reports that tirzepatide was associated with a lower urine albumin-to-creatinine ratio (UACR) than placebo over 72 weeks, without adverse changes in estimated kidney filtration ^[1]. UACR estimates how much protein leaks into the urine and is used as a signal of kidney stress.

Tirzepatide is the active ingredient in Mounjaro, used for type 2 diabetes, and Zepbound, used for obesity.

What the analysis looked at

SURMOUNT-1 enrolled 2,539 adults with overweight or obesity and without type 2 diabetes, who were assigned to tirzepatide 5, 10, or 15 mg once weekly or placebo. SURMOUNT-2 enrolled 938 adults with type 2 diabetes, assigned to tirzepatide 10 or 15 mg or placebo. For this analysis, all tirzepatide dose groups within each trial were pooled ^[1].

Median UACR at the start was 6.0 mg/g (25th–75th percentile, 4.0–11.0) in SURMOUNT-1 and 13.0 mg/g (6.0–35.1) in SURMOUNT-2 ^[1]. At week 72, the estimated difference for tirzepatide versus placebo was −8.4% (95% confidence interval [CI], −14.7 to −1.6) in SURMOUNT-1 and −31.1% (95% CI, −40.9 to −19.7) in SURMOUNT-2 ^[1].

The reductions were larger among participants who began with UACR of 30 mg/g or higher: placebo-corrected changes at week 72 of −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]. The abstract states that the UACR reduction appeared after 24 weeks and was sustained through week 72 ^[1].

Kidney filtration

Kidney filtration did not worsen. In SURMOUNT-1, tirzepatide was associated with higher estimated glomerular filtration rate (eGFR) on two estimating equations, with mean differences versus placebo at week 72 of 3.2 mL/min per 1.73 m2 (95% CI, 2.1 to 4.3) for cystatin-C–based eGFR and 1.9 mL/min per 1.73 m2 (95% CI, 0.9 to 2.9) for creatinine-cystatin-C–based eGFR ^[1]. In SURMOUNT-2, eGFR rose in both the tirzepatide and placebo groups on those equations, with no difference between the groups ^[1]. The authors concluded that tirzepatide was associated with reduced albuminuria without adverse changes in eGFR ^[1].

Limits of the findings

The results come from a post hoc analysis, meaning the kidney measures were examined after the trials were designed and were not primary endpoints of SURMOUNT-1 or SURMOUNT-2 ^[1]. The analysis reports a marker of kidney stress rather than hard outcomes such as kidney failure, dialysis, or transplant, and whether the UACR changes lead to fewer of those events has not been reported ^[1]. Most SURMOUNT-1 participants started with UACR in the normal range, so the average change in that trial was small ^[1]. Whether similar results would appear with semaglutide or other GLP-1 medicines has not been reported in this analysis ^[1].

Why it matters for patients

People with obesity or type 2 diabetes are at higher risk of progressive kidney function loss, and UACR is one of the measures used to track early kidney stress ^[1]. A fall in UACR on a treatment is a favorable signal, but it is not proof that a person will avoid kidney failure, because that question was not tested here ^[1].

The effect size differed by group: participants with type 2 diabetes saw a larger average reduction than those without, and the biggest reductions showed up in people who already had elevated albuminuria at the start ^[1]. That pattern is relevant for anyone whose lab reports include a UACR value, since it suggests the marker moved most where there was more room to move.

Nothing in the analysis changes approved uses or dosing of tirzepatide, and no new kidney-related indication or label change has been reported ^[1]. Readings of UACR and eGFR are interpreted by clinicians alongside other tests and a person's history, and this analysis does not say what any individual's numbers mean.

What happens next

The abstract lists trial registrations for SURMOUNT-1 (NCT04184622) and SURMOUNT-2 (NCT04657003), plus a third registration number, NCT05536804, without describing what that study is ^[1]. Longer-term data on whether albuminuria reductions translate into fewer kidney events, and dedicated kidney outcome trials of tirzepatide in people with obesity, have not been reported ^[1].