Tirzepatide outperforms semaglutide for HbA1c reduction, weight loss in type 2 diabetes
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Key takeaways:
- In a meta-analysis of randomized trials, tirzepatide was associated with larger HbA1c and weight reductions vs. placebo than semaglutide.
- Both drugs increased the risk for adverse gastrointestinal events.
Tirzepatide induced greater HbA1c and body weight reductions vs. placebo than semaglutide for people with type 2 diabetes, according to data that will be presented at the European Association for the Study of Diabetes annual meeting.
“The results can guide clinicians in personalizing treatment plans for their patients with type 2 diabetes,” Thomas Karagiannis, MD, PhD, MSc(Res), MSc(HTA), a clinical reader in internal medicine in the clinical research and evidence-based medicine unit at Aristotle University of Thessaloniki in Greece, told Healio. “Given its efficacy in controlling blood sugar and facilitating weight loss, tirzepatide could emerge as a preferred option for certain patients, especially for those where weight management is a priority. Nevertheless, decisions should always consider the complete safety profile of the drug, patient preferences and cost-effectiveness in certain health care settings.”
Researchers conducted a network meta-analysis of randomized controlled trials that assessed a maintenance dose of 5 mg, 10 mg or 15 mg once-weekly tirzepatide (Mounjaro, Eli Lilly) or 0.5 mg, 1 mg or 2 mg once-weekly subcutaneous semaglutide (Wegovy, Novo Nordisk) compared with placebo for at least 12 weeks. Trials were obtained from the MEDLINE and Cochrane Library databases. Researchers calculated mean differences between the medications and placebo for change from baseline in HbA1c and body weight. Risks for adverse events between the medications and placebo were also calculated.
There were 22 randomized controlled trials with 18,472 participants. Tirzepatide 15 mg conferred the largest HbA1c reduction with a 2% lower HbA1c compared with placebo. Tirzepatide 10 mg was associated with a 1.86% greater HbA1c reduction than placebo, and semaglutide 2 mg had the third-largest HbA1c reduction compared with placebo at 1.62%.
For change in body weight, all three tirzepatide doses outperformed semaglutide. Adults receiving tirzepatide 15 mg lost 10.96 kg more body weight than placebo, tirzepatide 10 mg induced an 8.75 kg greater weight loss than placebo and those receiving tirzepatide 5 mg lost 6.16 kg more body weight than placebo. Adults receiving high-dose semaglutide 2 mg lost 5.24 kg more body weight than placebo.
“One notable observation was the degree to which tirzepatide outperformed subcutaneous semaglutide in weight loss, especially in comparisons between the highest doses for both drugs,” Karagiannis said. “While both drugs have shown promise in individual trials, the magnitude of the difference is impressive.”
Of the six doses analyzed, tirzepatide 15 mg was associated with the highest risks for nausea (RR = 3.57; 95% CI, 2.56-4.76), vomiting (RR = 4.35; 95% CI, 3.03-6.25) and diarrhea (RR = 2.04; 95% CI, 1.56-2.63) compared with placebo. In between-drug comparisons, risks for adverse events were similar except adults receiving tirzepatide 15 mg had a greater risk for vomiting than those receiving semaglutide 1 mg and greater risks for vomiting and nausea than adults receiving semaglutide 0.5 mg. No differences in risks for serious adverse events were observed.
Karagiannis noted that the data supported the use of semaglutide for people with type 2 diabetes, but he said more studies are needed to assess cardiovascular and renal outcomes with the medication.
“Notably, a long-term CV trial is already underway comparing tirzepatide with dulaglutide (Trulicity, Eli Lilly), a glucose-lowering medication belonging to the GLP-1 receptor agonist class that has shown beneficial CV effects,” Karagiannis said. “In addition, valid country-specific cost-effectiveness evaluations comparing tirzepatide with semaglutide and other glucose-lowering medications (for example, SGLT2 inhibitors or other GLP-1 receptor agonists) are also required.”
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Karagiannis T, et al. Abstract 5. Presented at: European Association for the Study of Diabetes Annual Meeting; Oct. 2-6, 2023; Hamburg, Germany (hybrid meeting).
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