Tirzepatide linked to lower risk for death, adverse CV and kidney outcomes vs. GLP-1s
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Key takeaways:
- Adults with type 2 diabetes had a 42% lower risk for all-cause mortality if they used tirzepatide vs. a GLP-1.
- Tirzepatide was also linked to a lower risk for major adverse CV and kidney events.
Adults with type 2 diabetes have lower risks for death and major adverse cardiovascular and kidney events if they use tirzepatide compared with GLP-1 receptor agonists, according to observational data published in JAMA Network Open.
“This cohort study provided evidence supporting the association of tirzepatide treatment, compared to GLP-1 receptor agonists, with lower hazards of all-cause mortality and adverse CV or kidney events through a head-to-head comparison in patients with type 2 diabetes,” Vin-Cent Wu, MD, PhD, attending physician in the department of internal medicine at National Taiwan University Hospital, and colleagues wrote “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.”
Wu and colleagues analyzed data from the TriNetX U.S. Collaborative Network database of adults aged 18 years and older with type 2 diabetes who were prescribed tirzepatide (Mounjaro, Eli Lilly) or a GLP-1 receptor agonist from June 1, 2022, to June 20, 2023. Propensity score matching using 48 variables was conducted to match a group of adults prescribed tirzepatide, 1:1, with those prescribed a GLP-1. Researchers assessed all-cause mortality as the primary outcome. Major adverse CV events included myocardial infarction, ischemic or hemorrhagic stroke or CV death. Kidney events were defined as stage 5 chronic kidney disease, end-stage kidney disease or need for dialysis. Major adverse kidney events included the same three conditions as the kidney events category plus death. Acute kidney injury and a composite of all-cause mortality and major adverse CV events were also assessed. HbA1c and body weight were collected at 4, 8, 12, 16 and 20 months.
After a median 10.5 months of follow-up, adults using tirzepatide had a lower risk for all-cause mortality than those prescribed a GLP-1 (adjusted HR = 0.58; 95% CI, 0.45-0.75; P < .001). The risk for major adverse CV events (aHR = 0.8; 95% CI, 0.71-0.91; P < .001), kidney events (aHR = 0.52; 95% CI, 0.37-0.73; P < .001), acute kidney injury (aHR = 0.78; 95% CI, 0.7-0.88; P < .001), major adverse kidney events (aHR = 0.54; 95% CI, 0.44-0.67; P < .001) and a composite of major adverse CV events and all-cause mortality (aHR = 0.76; 95% CI, 0.68-0.84; P < .001) were also lower for adults prescribed tirzepatide vs. GLP-1 receptor agonists.
Adults prescribed tirzepatide had a 0.34 percentage point greater reduction in HbA1c and a 2.9 kg greater loss in body weight from baseline to 20 months than adults prescribed a GLP-1.
Researchers found no difference in findings during subgroup analyses where adults were stratified by estimated glomerular filtration rate; HbA1c; the presence of hypertension, ischemic heart disease, heart failure, proteinuria or diabetes complications; the use of other diabetes medication; previous use of GLP-1s; treatment indications; cholesterol level or BMI.
“Our findings also provide directions for future research in other target populations,” the researchers wrote. “The observational nature of our data precluded inference of causality, which might be confirmed in future research, such as in ongoing randomized controlled trials evaluating the efficacy of tirzepatide in improving CV and kidney outcomes compared with GLP-1 agonists and in treating patients with heart failure with preserved ejection fraction.”
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