Tirzepatide shows lower risk of mortality and adverse cardiovascular/kidney events than GLP-1 RAs in type 2 diabetes

The risk of mortality and adverse cardiovascular and kidney outcomes with tirzepatide—a dual glucagon-like peptide 1 and glucose-dependent insulinotropic polypeptide receptor agonist—compared with glucagon-like peptide 1 receptor agonists (GLP-1 RAs; e.g., semaglutide) remains unknown. To investigate this issue, researchers examined the association between tirzepatide and mortality and adverse cardiovascular and kidney outcomes compared with GLP-1 RAs in patients with type 2 diabetes.The retrospective cohort study used U.S. Collaborative Network of TriNetX data from adults (≥ 18 years of age) with type 2 diabetes who started tirzepatide or GLP-1 RA therapy between June 1, 2022, and June 30, 2023. The study excluded patients with stage 5 chronic kidney disease or kidney failure at baseline, as well as those who developed myocardial infarction or ischemic or hemorrhagic stroke within the 60-day period before drug initiation. The primary outcome was all-cause mortality. Secondary outcomes were major adverse cardiovascular events (MACEs; including myocardial infarction, ischemic or hemorrhagic stroke, or cardiac death), the composite of MACEs and all-cause mortality, kidney events, acute kidney injury, and major adverse kidney events. Key results are summarized below:The study included 14,834 patients treated with tirzepatide (mean age, 55.4 years; 56.9% female) and 125,474 treated with a GLP-1 RA (mean age, 58.1 years; 53.8% female). After a median follow-up of 10.5 months, 95 patients (0.6%) in the tirzepatide group and 166 (1.1%) in the GLP-1 RA group died. Tirzepatide treatment was associated with lower hazards of all-cause mortality (adjusted hazard ratio [AHR], 0.58; 95%CI, 0.45–0.75), MACEs (AHR, 0.80; 95%CI, 0.71–0.91), the composite of MACEs and all-cause mortality (AHR, 0.76; 95%CI, 0.68–0.84), kidney events (AHR, 0.52; 95%CI, 0.37–0.73), acute kidney injury (AHR, 0.78; 95%CI, 0.70–0.88), and major adverse kidney events (AHR, 0.54; 95%CI, 0.44–0.67). Treatment with tirzepatide was associated with greater decreases in glycated hemoglobin (A1C; 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) compared with GLP-1 RAs. Subgroup analysis revealed consistent results stratified by estimated glomerular filtration rate, A1C level, body mass index, co-medications and comorbidities.This study provides evidence that tirzepatide therapy is associated with lower hazards of all-cause mortality, adverse cardiovascular events, acute kidney injury and adverse kidney events compared with GLP-1 RAs in patients with type 2 diabetes. The authors conclude that their findings support the integration of tirzepatide into therapeutic strategies for managing patients with type 2 diabetes.Reference:Chuang MH, Chen JY, Wang HY, et al. Clinical outcomes of tirzepatide or GLP-1 receptor agonists in individuals with type 2 diabetes. JAMA Network Open 2024;7(8):e2427258. (accessed August 13, 2024).

Tirzepatide shows lower risk of mortality and adverse cardiovascular/kidney events than GLP-1 RAs in type 2 diabetes

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