SURPASS-CVOT kidney analysis reports a 23% lower rate of major kidney events

People with type 2 diabetes and heart disease who took tirzepatide had a 23% lower rate of major kidney events than those who took dulaglutide, according to a prespecified exploratory analysis of the SURPASS-CVOT trial ^[1]. The composite kidney outcome occurred in 396 participants (6.0%) assigned to tirzepatide and 498 (7.6%) assigned to dulaglutide, a hazard ratio of 0.77 (95% CI 0.68 to 0.88; p=0.0002) ^[1].

SURPASS-CVOT was a randomized, double-blind trial comparing two active drugs rather than a drug against placebo. Participants were assigned 1:1 to once-weekly injections of either tirzepatide, titrated up to 15 mg, or dulaglutide 1.5 mg ^[1]. Tirzepatide is sold in the US as Mounjaro for type 2 diabetes and Zepbound for weight-related conditions. The trial enrolled at 640 sites in 30 countries between May 29, 2020 and June 27, 2022, and required participants to be 40 or older with type 2 diabetes, atherosclerotic cardiovascular disease, an HbA1c between 7% and 10.5%, and a BMI of at least 25 kg/m² ^[1]. Of 16,979 people screened, 13,299 were randomly assigned; after excluding 134 assigned in error, 6,586 received tirzepatide and 6,579 received dulaglutide ^[1]. Median follow-up was 4.0 years (IQR 3.7–4.4) ^[1]. The trial was funded by Eli Lilly and Company, which makes tirzepatide ^[1].

What the kidney outcome measured

The composite kidney outcome was the time to the first of these events: persistent macroalbuminuria (high levels of protein in the urine), a persistent drop of 50% or more in estimated glomerular filtration rate (eGFR), end-stage kidney disease (eGFR under 15 mL/min per 1.73 m² or starting long-term dialysis or transplant), or death from kidney disease ^[1].

Kidney problems were already common at baseline. Among participants with data, 4,142 of 12,954 (32.0%) had microalbuminuria and 1,491 (11.5%) had macroalbuminuria, while 2,928 of 13,004 (22.5%) had an eGFR below 60 mL/min per 1.73 m² ^[1]. A total of 2,948 participants met the trial's definition of high-risk chronic kidney disease ^[1].

The benefit appeared in both risk groups. Among those with low-to-moderate-risk chronic kidney disease, events occurred in 195 (4.0%) on tirzepatide versus 283 (5.6%) on dulaglutide (HR 0.70, 95% CI 0.58 to 0.84; p=0.0001) ^[1]. Among those with high-risk chronic kidney disease, events occurred in 185 (12.2%) versus 203 (14.5%) (HR 0.79, 95% CI 0.64 to 0.96; p=0.018) ^[1]. The authors say the overall result was driven mainly by fewer new cases of persistent macroalbuminuria in the lower-risk group and by slower loss of kidney function in the higher-risk group ^[1].

Kidney function declined more slowly on tirzepatide. The between-group difference in annual eGFR decline was 0.29 mL/min per 1.73 m² per year in the overall population (95% CI 0.17 to 0.41; p<0.0001) and 0.93 mL/min per 1.73 m² per year in the high-risk group (95% CI 0.65 to 1.22; p<0.0001) ^[1]. Nausea, vomiting, and diarrhea were all more common with tirzepatide than with dulaglutide ^[1].

Why it matters for patients

Kidney disease is one of the most common and costly complications of type 2 diabetes, and albuminuria is an early warning sign that often precedes dialysis years later. These results suggest that, in people who also have established heart disease, tirzepatide slowed that process more than dulaglutide did over four years ^[1].

Several limits matter. The analysis was exploratory, not the trial's primary endpoint, which was a composite cardiovascular outcome for which tirzepatide was non-inferior to dulaglutide ^[1]. Exploratory findings are generally treated as hypothesis-generating rather than definitive. The comparison was against dulaglutide 1.5 mg, not against placebo or against other GLP-1 drugs such as semaglutide, so the results do not say how tirzepatide compares with those options. Everyone enrolled had both type 2 diabetes and atherosclerotic cardiovascular disease, so it is not known from this analysis whether the same pattern holds in people without heart disease or without diabetes. The absolute difference in the overall population was about 1.6 percentage points over four years ^[1].

What happens next

The sources do not say whether Eli Lilly will seek a kidney-related label change from the US Food and Drug Administration, or when guideline groups might weigh in. Those steps are not yet known.