Real-World Analysis Finds Tirzepatide Offers Greater Benefit than GLP-1 RAs for Heart, Kidney in T2D

Vin-cent Wu, MD, PhD

Credit: Primary Aldosteronism Foundation

An analysis of real-world data from more than 140,000 people with type 2 diabetes suggests tirzepatide (Mounjaro) provided greater benefit than GLP-1 receptor agonists on mortality, cardiovascular risk, and risk of kidney events.

Leveraging data from the TriNetX database, investigators compared real-world data from more than 14,000 tirzepatide users and 125,000 GLP-1 receptor agonist users, investigators found patients using tirzepatide had a 42%, 20%, and 46% relative reductions in risk for all-cause mortality, major adverse cardiovascular events (MACE), major adverse kidney events, respectively, relative to their counterparts receiving GLP-1 receptor agonists.¹

“We have for the first time to our knowledge presented evidence substantiating that tirzepatide therapy is associated with lower risks of all-cause mortality, MACEs, [major adverse kidney events], and [acute kidney injury] compared with GLP-1 RA therapy after a median follow-up of 10.5 months,” wrote investigators.¹

Few happenings in medicine have permeated the public consciousness in the same fashion as the revelations of the benefits of incretin therapies beyond glycemic control, driven primarily by phase 3 findings from trials of semaglutide (Ozempic) and tirzepatide. Without head-to-head randomized trials, many have turned to indirect comparisons of the agents using trial or real-world electronic health record data.^1,2

In the current study, a team of investigators led by Vin-Cent Wu, MD, PhD, of the National Taiwan University Hospital, sought to compare the rate of hard outcomes among users of tirzepatide and GLP-1 receptor agonists using data from the US Collaborative Network of TriNetX data. With June 1, 2022 and June 30, 2023 as the period of interest, investigators performed a search for individuals with type 2 diabetes aged 18 years or older initiating treatment with tirzepatide or a GLP-1 receptor agonist for inclusion in the current study. Additional inclusion criteria required patients to be without stage 5 chronic kidney disease or kidney failure at baseline and with myocardial infarction or ischemic or hemorrhagic stroke within 60 days of drug initiation.¹

A total of 14,834 patients initiation therapy with tirzepatide and 125,747 patients initiating treatment with a GLP-1 receptor agonist were identified for inclusion. The tirzepatide cohort had a mean age of 55.4 (SD, 11.8) years and 56.9% were female. The GLP-1 receptor agonist cohort had a mean age of 58.1 (SD, 13.3) years and 53.8% were female. For the purpose of analysis, investigators matched those in the tirzepatide cohort to 14,834 patients in the GLP-1 receptor against cohort using 48 variables covering demographics, comorbidities, medications, and laboratory results.¹

The primary outcome of interest for the study was the relative risk of all-cause mortality with tirzepatide relative to GLP-1 receptor agonist therapy. The study’s secondary outcomes included MACE, a composite of MACE and all-cause mortality, kidney events, acute kidney injury (AKI), and major adverse kidney events. Investigators pointed out risk was estimated using Cox proportional hazards regression models.¹

During the follow-up period, which lasted a median of 10.5 (IQR, 5.2 to 15.6) months, 0.6% of the tirzepatide group and 1.1% of the GLP-1 receptor agonist group died. Results of the investigators’ analyses suggested use of tirzepatide was associated with a reduced risk of all-cause mortality (adjusted hazard ratio [aHR], 0.58; 95%CI, 0.45 to 0.75), MACE (aHR, 0.80; 95% CI, 0.71 to 0.91),the composite of MACE and all-cause mortality (aHR, 0.76; 95% CI, 0.68 to 0.84), kidney events (aHR, 0.52; 95%CI, 0.37 to 0.73), AKI (aHR, 0.78; 95%CI, 0.70 to 0.88), and major adverse kidney events (aHR, 0.54; 95%CI, 0.44 to 0.67) relative to GLP-1 receptor agonist use (P for all <.001).¹

Further analysis revealed use of tirzepatide was associated with greater reductions in HbA1c (treatment difference, −0.34 percentage points; 95%CI, −0.44 to −0.24 percentage points) and body weight (treatment difference, −2.9 kg, 95%CI, −4.8 to −1.1 kg) than use of GLP-1 receptor agonists. Additionally, investigators highlighted subgroup analysis suggested these results were consistent irrespective of stratification by eGFR, HbA1c, BMI, polypharmacy, and comorbidities.¹

“This cohort study provided evidence supporting the association of tirzepatide treatment, compared to GLP-1 RAs, with lower hazards of all-cause mortality and adverse cardiovascular or kidney events through a head-to-head comparison in patients with type 2 diabetes. These insights advocate for the integration of tirzepatide into therapeutic strategies for managing type 2 diabetes and highlight its potential to enhance current clinical practice,” investigators added.¹

References:

1. Chuang M, Chen J, Wang H, Jiang Z, Wu V. Clinical Outcomes of Tirzepatide or GLP-1 Receptor Agonists in Individuals With Type 2 Diabetes. JAMA Netw Open. 2024;7(8):e2427258. doi:10.1001/jamanetworkopen.2024.27258
2. Campbell P, Iapoce C. 10 years of obesity: A Decade of Advancement and challenges. HCP Live. June 23, 2023. Accessed August 12, 2024. https://www.hcplive.com/view/10-years-of-obesity-a-decade-of-advancement-and-challenges.