A comparison of the effects of tirzepatide and dulaglutide on major kidney events in people with type 2 diabetes: pre-specified exploratory analyses of the SURPASS-CVOT trial
18 affiliations
- 1School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia; Victorian Heart Institute, Monash University, Melbourne, VIC, Australia. Electronic address: [email protected]
- 2Duke University Medical Center, Durham, NC, USA
- 3Eli Lilly and Company, Indianapolis, IN, USA
- 4Mount Sinai Fuster Heart Hospital, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- 5University of North Carolina, Chapel Hill, NC, USA
- 6Interdisciplinary Research Center "Health Science," Sant'Anna School of Advanced Studies, Pisa, Italy
- 7Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, VA Puget Sound Health Care System and University of Washington, Seattle, WA, USA
- 8Department of Cardiovascular Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH, USA
- 9University of Texas Southwestern Medical Center and Parkland Health System, Dallas, TX, USA
- 10Diabetes, Endocrinology and Metabolism Section, Department of Medicine, St Josef-Hospital, Katholisches Klinikum Bochum, Ruhr University of Bochum, Bochum, Germany
- 11Cleveland Clinic Coordinating Center for Clinical Research (C5 Research) and Department of Medicine, Cleveland Clinic, Cleveland, OH, USA
- 12School of Cardiovascular Medicine and Metabolic Health, University of Glasgow, Glasgow, UK
- 13University of Toronto, Lunenfeld-Tanenbaum Research Institute and Mount Sinai Hospital, Toronto, ON, Canada
- 14IRCCS MultiMedica, Milan, Italy
- 15Department of Internal Medicine I, Paracelsus Medical University, Salzburg, Austria
- 16Department of Endocrinology, Diabetes and Metabolism, Antwerp University Hospital, Edegem, and ZAS Jan Palfijn, Merksem, Belgium
- 17Monash University Clinical Trials Centre, Monash University, Melbourne, VIC, Australia
- 18Victorian Heart Institute, Monash University, Melbourne, VIC, Australia
Abstract
Background In the SURPASS-CVOT trial, tirzepatide, a dual incretin agonist that targets the glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptors, was shown to be non-inferior to dulaglutide for the primary composite cardiovascular outcome in people with type 2 diabetes and atherosclerotic cardiovascular disease. Here, we report the results of a pre-specified exploratory analysis of SURPASS-CVOT that aimed to assess major kidney events in the overall population, low-to-moderate-risk chronic kidney disease population, and high-risk chronic kidney disease population. Methods SURPASS-CVOT was a randomised, active comparator-controlled, double-blind trial that enrolled people with type 2 diabetes and atherosclerotic cardiovascular disease at 640 sites in 30 countries. Participants aged 40 years or older with type 2 diabetes and atherosclerotic cardiovascular disease, HbA 1c between 7% and 10·5%, and a BMI of 25 kg/m 2 or greater were randomly assigned 1:1 to once-weekly blinded subcutaneous injection of either tirzepatide up to 15 mg or dulaglutide 1·5 mg. Annual visits included assessment of serum creatinine, cystatin C, and urine albumin-to-creatinine ratio (UACR). High-risk chronic kidney disease was defined by an estimated glomerular filtration rate (eGFR) of 60 mL/min per 1·73 m 2 or greater and UACR greater than 300 mg/g; eGFR 45 mL/min per 1·73 m 2 to less than 60 mL/min per 1·73 m 2 and UACR greater than 30 mg/g; or eGFR less than 45 mL/min per 1·73 m 2 , with eGFR calculated with the CKD-Epidemiology Collaboration serum creatinine-cystatin C equation. The primary composite kidney outcome was time to first occurrence of persistent macroalbuminuria, persistent reduction in eGFR of 50% or greater, end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 or initiation of chronic kidney replacement therapy), or death from kidney disease. Findings Between May 29, 2020, and June 27, 2022, 16 979 participants were screened and 13 299 (2948 with high-risk chronic kidney disease) were randomly assigned. After excluding 134 participants randomly assigned in error, 6586 were assigned to tirzepatide and 6579 were assigned to dulaglutide. At baseline, 4142 (32·0%) of 12 954 participants had microalbuminuria and 1491 (11·5%) of 12 954 had macroalbuminuria, and 2928 (22·5%) of 13 004 had an eGFR less than 60 mL/min per 1·73 m 2 . After a median follow-up of 4·0 (IQR 3·7–4·4) years, the risk of the primary composite kidney outcome in the overall population was 23% lower with tirzepatide than with dulaglutide (396 [6·0%] vs 498 [7·6%] events, hazard ratio 0·77 [95% CI 0·68 to 0·88], p=0·0002) and was similarly reduced in those with low-to-moderate-risk chronic kidney disease (195 [4·0%] vs 283 [5·6%], 0·70 [0·58 to 0·84], p=0·0001) and those with high-risk chronic kidney disease (185 [12·2%] vs 203 [14·5%], 0·79 [95% CI 0·64 to 0·96], p=0·018). This was primarily driven by a lower rate of new-onset persistent macroalbuminuria in those with low-to-moderate-risk chronic kidney disease and a lower rate of eGFR decline in those with high-risk chronic kidney disease. Observations were consistent in all other subgroups examined. The annual rate of decline in eGFR was lower with tirzepatide than with dulaglutide in the overall population (between-group difference 0·29 mL/min per 1·73 m 2 [95% CI 0·17 to 0·41]; p<0·0001) and in those with high-risk chronic kidney disease (0·93 mL/min per 1·73 m 2 [0·65 to 1·22], p<0·0001). Nausea, vomiting, and diarrhoea were all more common in those receiving tirzepatide than in those receiving dulaglutide. Interpretation Among people with type 2 diabetes and atherosclerotic cardiovascular disease, tirzepatide was associated with a reduced risk of major kidney events compared with dulaglutide, primarily driven by a reduction in new-onset macroalbuminuria in people with low-to-moderate-risk chronic kidney disease, and slowed decline in kidney function in people with high-risk chronic kidney disease. Funding Eli Lilly and Company.
Related
- Exit Interviews Examining Patient Experiences with Tirzepatide and Dulaglutide for Treatment of Type 2 Diabetes in the SURPASS-CVOT Trial
- Biliary and Pancreatic Safety of Incretin-Based Therapies in Obesity and Type 2 Diabetes: A Propensity-Matched Real-World Comparison of Tirzepatide, Semaglutide, and DPP-4 Inhibitors
- Efficacy and safety of mazdutide vs. dulaglutide in adults with type 2 diabetes: a systematic review and meta-analysis of randomized controlled trials.
- Clinical outcomes of tirzepatide in a real-world follow-up cohort of patients with type 2 diabetes
- Atypical Anorexia Nervosa Developed in a Patient with Severe Obesity and Type 2 Diabetes Following Sleeve Gastrectomy and Postoperative Treatment with Semaglutide and Tirzepatide
BibTeX
@article{zoungas2026comparison,
title = {{A comparison of the effects of tirzepatide and dulaglutide on major kidney events in people with type 2 diabetes: pre-specified exploratory analyses of the SURPASS-CVOT trial}},
author = {Sophia Zoungas and David A. D’Alessio and Imre J. Pavo and Deepak L. Bhatt and John B. Buse and Stefano Del Prato and Steven E. Kahn and A Michael Lincoff and Darren K. McGuire and Michael Albrecht Nauck and Steven E. Nissen and Naveed A. Sattar and Bernard Zinman and Antonio Ceriello and Lars Stechemesser and Ann Verhaegen and Jonathan C. Broder and Rory Wolfe and Debra Miller and Hiroshi Nishiyama and Xiaomei Wang and Govinda J. Weerakkody and Russell J. Wiese and Stephen J Nicholls},
journal = {The Lancet Diabetes \& Endocrinology},
year = {2026},
month = may,
doi = {10.1016/s2213-8587(26)00032-x},
url = {https://doi.org/10.1016/s2213-8587(26)00032-x},
note = {CC BY},
}
RIS
TY - JOUR
TI - A comparison of the effects of tirzepatide and dulaglutide on major kidney events in people with type 2 diabetes: pre-specified exploratory analyses of the SURPASS-CVOT trial
AU - Sophia Zoungas
AU - David A. D’Alessio
AU - Imre J. Pavo
AU - Deepak L. Bhatt
AU - John B. Buse
AU - Stefano Del Prato
AU - Steven E. Kahn
AU - A Michael Lincoff
AU - Darren K. McGuire
AU - Michael Albrecht Nauck
AU - Steven E. Nissen
AU - Naveed A. Sattar
AU - Bernard Zinman
AU - Antonio Ceriello
AU - Lars Stechemesser
AU - Ann Verhaegen
AU - Jonathan C. Broder
AU - Rory Wolfe
AU - Debra Miller
AU - Hiroshi Nishiyama
AU - Xiaomei Wang
AU - Govinda J. Weerakkody
AU - Russell J. Wiese
AU - Stephen J Nicholls
PY - 2026
DA - 2026/05/14
JO - The Lancet Diabetes & Endocrinology
DO - 10.1016/s2213-8587(26)00032-x
UR - https://doi.org/10.1016/s2213-8587(26)00032-x
AB - Background In the SURPASS-CVOT trial, tirzepatide, a dual incretin agonist that targets the glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptors, was shown to be non-inferior to dulaglutide for the primary composite cardiovascular outcome in people with type 2 diabetes and atherosclerotic cardiovascular disease. Here, we report the results of a pre-specified exploratory analysis of SURPASS-CVOT that aimed to assess major kidney events in the overall population, low-to-moderate-risk chronic kidney disease population, and high-risk chronic kidney disease population. Methods SURPASS-CVOT was a randomised, active comparator-controlled, double-blind trial that enrolled people with type 2 diabetes and atherosclerotic cardiovascular disease at 640 sites in 30 countries. Participants aged 40 years or older with type 2 diabetes and atherosclerotic cardiovascular disease, HbA 1c between 7% and 10·5%, and a BMI of 25 kg/m 2 or greater were randomly assigned 1:1 to once-weekly blinded subcutaneous injection of either tirzepatide up to 15 mg or dulaglutide 1·5 mg. Annual visits included assessment of serum creatinine, cystatin C, and urine albumin-to-creatinine ratio (UACR). High-risk chronic kidney disease was defined by an estimated glomerular filtration rate (eGFR) of 60 mL/min per 1·73 m 2 or greater and UACR greater than 300 mg/g; eGFR 45 mL/min per 1·73 m 2 to less than 60 mL/min per 1·73 m 2 and UACR greater than 30 mg/g; or eGFR less than 45 mL/min per 1·73 m 2 , with eGFR calculated with the CKD-Epidemiology Collaboration serum creatinine-cystatin C equation. The primary composite kidney outcome was time to first occurrence of persistent macroalbuminuria, persistent reduction in eGFR of 50% or greater, end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 or initiation of chronic kidney replacement therapy), or death from kidney disease. Findings Between May 29, 2020, and June 27, 2022, 16 979 participants were screened and 13 299 (2948 with high-risk chronic kidney disease) were randomly assigned. After excluding 134 participants randomly assigned in error, 6586 were assigned to tirzepatide and 6579 were assigned to dulaglutide. At baseline, 4142 (32·0%) of 12 954 participants had microalbuminuria and 1491 (11·5%) of 12 954 had macroalbuminuria, and 2928 (22·5%) of 13 004 had an eGFR less than 60 mL/min per 1·73 m 2 . After a median follow-up of 4·0 (IQR 3·7–4·4) years, the risk of the primary composite kidney outcome in the overall population was 23% lower with tirzepatide than with dulaglutide (396 [6·0%] vs 498 [7·6%] events, hazard ratio 0·77 [95% CI 0·68 to 0·88], p=0·0002) and was similarly reduced in those with low-to-moderate-risk chronic kidney disease (195 [4·0%] vs 283 [5·6%], 0·70 [0·58 to 0·84], p=0·0001) and those with high-risk chronic kidney disease (185 [12·2%] vs 203 [14·5%], 0·79 [95% CI 0·64 to 0·96], p=0·018). This was primarily driven by a lower rate of new-onset persistent macroalbuminuria in those with low-to-moderate-risk chronic kidney disease and a lower rate of eGFR decline in those with high-risk chronic kidney disease. Observations were consistent in all other subgroups examined. The annual rate of decline in eGFR was lower with tirzepatide than with dulaglutide in the overall population (between-group difference 0·29 mL/min per 1·73 m 2 [95% CI 0·17 to 0·41]; p<0·0001) and in those with high-risk chronic kidney disease (0·93 mL/min per 1·73 m 2 [0·65 to 1·22], p<0·0001). Nausea, vomiting, and diarrhoea were all more common in those receiving tirzepatide than in those receiving dulaglutide. Interpretation Among people with type 2 diabetes and atherosclerotic cardiovascular disease, tirzepatide was associated with a reduced risk of major kidney events compared with dulaglutide, primarily driven by a reduction in new-onset macroalbuminuria in people with low-to-moderate-risk chronic kidney disease, and slowed decline in kidney function in people with high-risk chronic kidney disease. Funding Eli Lilly and Company.
SN - 2213-8587
SN - 2213-8595
ER -