Prespecified SURPASS-CVOT analysis finds 23% fewer major kidney events with tirzepatide than dulaglutide

People with type 2 diabetes and atherosclerotic cardiovascular disease who took tirzepatide had fewer major kidney events than those who took dulaglutide in a prespecified exploratory analysis of the SURPASS-CVOT trial ^[1]. The composite kidney outcome occurred in 396 of 6,586 people on tirzepatide (6.0%) and 498 of 6,579 on dulaglutide (7.6%), a hazard ratio of 0.77 (95% CI 0.68 to 0.88; p=0.0002), after a median follow-up of 4.0 years (IQR 3.7 to 4.4) ^[1].

How the trial was set up

SURPASS-CVOT enrolled people aged 40 or older with type 2 diabetes and atherosclerotic cardiovascular disease, an HbA1c between 7% and 10.5%, and a BMI of 25 kg/m² or higher, at 640 sites in 30 countries ^[1]. Between May 29, 2020, and June 27, 2022, 16,979 people were screened and 13,299 were randomly assigned; after 134 were excluded because they had been randomly assigned in error, 6,586 were assigned to tirzepatide up to 15 mg once weekly and 6,579 to dulaglutide 1.5 mg once weekly, both given as blinded subcutaneous injections ^[1]. Annual visits included measurement of serum creatinine, cystatin C and urine albumin-to-creatinine ratio ^[1].

The kidney outcome combined the first occurrence of persistent macroalbuminuria, a persistent reduction in estimated glomerular filtration rate (eGFR) of 50% or greater, end-stage kidney disease, or death from kidney disease ^[1]. At baseline, 4,142 of 12,954 participants (32.0%) had microalbuminuria, 1,491 of 12,954 (11.5%) had macroalbuminuria, and 2,928 of 13,004 (22.5%) had an eGFR below 60 mL/min per 1.73 m² ^[1]. Of those randomly assigned, 2,948 had high-risk chronic kidney disease ^[1].

What the analysis found

The result was similar in both kidney risk groups. In the low-to-moderate-risk chronic kidney disease group, the outcome occurred in 195 people on tirzepatide (4.0%) versus 283 on dulaglutide (5.6%), a hazard ratio of 0.70 (95% CI 0.58 to 0.84; p=0.0001) ^[1]. In the high-risk group, it occurred in 185 (12.2%) versus 203 (14.5%), a hazard ratio of 0.79 (95% CI 0.64 to 0.96; p=0.018) ^[1].

The reason for the difference varied by group. The overall result was driven primarily by fewer new cases of persistent macroalbuminuria among people with low-to-moderate-risk chronic kidney disease, and by a slower loss of kidney function among people with high-risk chronic kidney disease ^[1]. The yearly decline in eGFR was smaller with tirzepatide than with dulaglutide, by 0.29 mL/min per 1.73 m² (95% CI 0.17 to 0.41) in the overall population and by 0.93 mL/min per 1.73 m² (0.65 to 1.22) in the high-risk group ^[1]. The authors report that observations were consistent in all other subgroups examined ^[1].

Nausea, vomiting and diarrhoea were all more common in people receiving tirzepatide than in those receiving dulaglutide ^[1]. The trial was funded by Eli Lilly and Company, and several authors are employees and shareholders of the company ^[1].

Why it matters for patients

Kidney damage is a common complication of type 2 diabetes, and macroalbuminuria — protein leaking into the urine — is one of the earliest signs. This analysis suggests that, in this specific population, tirzepatide was better than dulaglutide at preventing that early sign and at slowing the yearly loss of kidney function. The difference in the main outcome was 1.6 percentage points in absolute terms (6.0% versus 7.6%), which is the figure that describes how many people were affected, rather than the 23% relative reduction ^[1].

The comparison was between two drugs, not between a drug and a placebo, so the analysis shows how tirzepatide compared with dulaglutide and not how either compares with no treatment ^[1]. The analysis was prespecified but exploratory, meaning it was not the trial's primary endpoint, so it is generally treated as a signal that needs confirmation rather than proof. No results are reported here comparing tirzepatide with semaglutide or with other GLP-1 medications, and it is not yet known whether the kidney findings extend to people who do not have type 2 diabetes or who do not have atherosclerotic cardiovascular disease. Whether the analysis changes any prescribing information has not been reported.