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Patients receiving tirzepatide were significantly more likely to achieve clinically meaningful weight loss compared with those treated receiving semaglutide

Individuals with overweight or obesity treated with tirzepatide were significantly more likely to achieve clinically meaningful weight loss and larger reductions in body weight compared with those treated with semaglutide according to reseachers from Truveta, a medical research collective, and the Cardiovascular Analytics, Research and Data Science at Providence Heart Institute, Providence Health System, Portland, Oregon.

The study authors stated that although tirzepatide and semaglutide have been shown to reduce weight in randomised clinical trials, data from head-to-head comparisons in populations with overweight or obesity are not yet available. Therefore, the compared on-treatment weight loss and rates of gastrointestinal adverse events (AEs) among adults with overweight or obesity receiving either tirzepatide or semaglutide labelled for type 2 diabetes (T2D) in a clinical setting.

The main outcomes were on-treatment weight change in a propensity score–matched population, assessed as hazard of achieving 5% or greater, 10% or greater and 15% or greater weight loss, and percentage change in weight at three, six, and 12 months. In addition, gastrointestinal AEs were compared.


From 41,222 adults meeting the study criteria (semaglutide, 32 029; tirzepatide, 9193), 1, 386 remained after propensity score matching. The mean age was 52.0 (12.9) years, 12 970 were female (70.5%), 14 182 were white (77.1%), 2171 Black (11.8%), 354 Asian (1.9%), 1,679 were of other or unknown race, and 9563 (52.0%) had T2D. The mean baseline weight was 110 (25.8) kg. Follow-up was ended by discontinuation for 5,140 patients (55.9%) receiving tirzepatide and 4,823 (52.5%) receiving semaglutide. The mean (median) duration of on-treatment follow-up was 165 (129; IQR, 75-231; difference, 156) days.

Patients receiving tirzepatide were significantly more likely to achieve weight loss (≥5%; hazard ratio [HR], 1.76, 95% CI, 1.68, 1.84; ≥10%; HR, 2.54; 95% CI, 2.37, 2.73; and ≥15%; HR, 3.24; 95% CI, 2.91, 3.61). On-treatment changes in weight were larger for patients receiving tirzepatide at three months (difference, −2.4%; 95% CI −2.5% to −2.2%), six months (difference, −4.3%; 95% CI, −4.7% to −4.0%) and 12 months (difference, −6.9%; 95% CI, −7.9% to −5.8%). Interestingly, rates of gastrointestinal AEs were similar between groups.

After adjusting for residual confounding, the absolute difference in weight loss between tirzepatide and semaglutide was −2.4% (95% CI, −2.5% to −2.2), −4.3% (95% CI, −4.7% to −4.0%), and −6.9% (95% CI, −7.9% to −5.8%) at three, six, and 12 months receiving treatment, respectively.

“Consistent treatment effect estimates were observed in subgroups with and without T2D,” the authors concluded. “ Future work is needed to compare the effect of tirzepatide and semaglutide on other key end points (eg, reduction in major adverse cardiovascular events).”

The findings were featured in the paper, ‘Semaglutide vs Tirzepatide for Weight Loss in Adults With Overweight or Obesity’, published in JAMA Internal Medicine. To access this paper, please click here


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