Tirzepatide Demonstrates Efficacy for Reducing Weight in Overweight and Obesity

Tirzepatide demonstrates superior weight loss reduction compared with other glucose-lowering agents and has a safety profile similar to other weight loss drugs, according to research published in the International Journal of Obesity.

Researchers performed a meta-analysis of randomized controlled trials (n=7) that compared weight loss efficacy between tirzepatide and another weight loss drug or placebo. Among the trials included in the investigation, 6 used tirzepatide doses of 5 mg and 10 mg, and all 7 examined treatment with 15 mg doses. A total of 3 used placebos as a control, 2 used insulin, and 1 used semaglutide. Primary outcomes were percentage change in body weight from baseline and the proportion of participants achieving a 5% or greater weight loss. Secondary outcomes included changes in body weight, waist circumference, lipid profile, and blood pressure.

Overall, the meta-analysis included 5950 study participants — 5800 underwent treatment with tirzepatide and had available weight loss percentage data. Among these participants, 78.22% (95% CI, 72.15%-83.73%), 55.60% (95% CI, 46.54%-64.47%), and 32.28% (95% CI, 23.17%-42.12%) achieved total weight loss equal to greater than 5%, 10%, and 15%, respectively. The team noted a dose dependent effect, observing weight loss of 5% or greater in 65.91% (95% CI, 53.92%-76.95%), 80.72% (95% CI, 75.42%-85.52%) and 86.95% (95% CI, 84.42%-89.29%) in patients treated with 5 mg, 10 mg, and 15 mg, respectively. The odds of achieving 5% or greater weight loss compared with placebo were 10.95 (95% CI, 8.33-14.40), 15.33 (95% CI, 11.40-20.63) and 19.06 (95% CI, 13.88-26.18) with 5 mg, 10 mg, and 15 mg doses, respectively.

Compared with semaglutide, the odds of achieving weight loss of 5% or more were 1.50 (95% CI, 1.15-1.96), 3.05 (95% CI, 2.27-4.08) and 4.25 (95% CI, 3.10-5.82) among individuals treated with the 5 mg, 10 mg, and 15 mg tirzepatide doses, respectively.

A total of 6.22% (95% CI, 4.64%-7.97%) of participants reported serious adverse events, and 6.34% (95% CI, 5.04%-7.76%) discontinued therapy. Gastrointestinal adverse events were the most prevalent (18.42%; 95% CI, 4.74%-38.27%) and primarily consisted of diarrhea (16.02%; 95% CI, 14.10%-18.02%) and nausea (10.24%; 95% CI, 5.54%-16.02%).

“There is a paradigm shift in the treatment approach of metabolic diseases towards care of the overall metabolic milieu rather than individual components; these can potentially be achieved by tirzepatide as it targets multiple aspects of metabolic syndrome concurrently,” according to the study authors.

Study limitations include potential confounding due to a failure to consider exercise and diet and the inclusion of patients with diabetes in 6 of the 7 studies in the meta-analysis.