Tirzepatide Bests Semaglutide in Real-World Weight Loss Analysis


A study of 18,000 patients showed tirzepatide (Mounjaro) led to more significant weight loss than semaglutide (Ozempic) in adults with overweight or obesity.

Nicholas Stucky, MD, PhD | Credit: LinkedIn

Nicholas Stucky, MD, PhD
Credit: LinkedIn

An analysis of real-world data from more than 9000 matched pairs of patients receiving semaglutide (Ozempic) and tirzepatide (Mounjaro in doses for type 2 diabetes suggests the dual GIP/GLP-1 receptor agonist tirzepatide induced greater weight loss than its GLP-1 receptor agonist counterpart semaglutide.

“GLP-1 medications have dramatically increased in use by patients with and without type 2 diabetes in the past year, yet little real-world data exist to compare the effectiveness of two of the most common medications, semaglutide and tirzepatide,” said study investigator Tricia Rodriguez, PhD, MPH principal applied scientist at Truveta Research.2 “That’s what makes today’s study findings so exciting and important. Because Truveta Data provides timely, complete EHR data – including prescriptions and medication dispense data – that captures a large and diverse patient population, we’ve been able to compare the head-to-head efficacy of these two important medications for weight loss in advance of smaller randomized clinical trials. This study can help to inform patient care and outcomes today, not months from now.”

With the backdrop of a growing obesity epidemic, the revelations of the weight loss benefits of GLP-1 receptor agonist semaglutide and other incretin therapies, namely tirzepatide, have placed these medications firmly at the center of conversations among medical professionals and laypersons alike. Although tirzepatide was examined against semaglutide 1.0 mg in people with type 2 diabetes in the SURPASS-2 trial, additional dosages of the agent have received approval since this trial launched in and limited data exists related to the comparative weight loss effects beyond clinical trial settings.1,3,4

With this in mind, a team led by Nicholas L. Stucky, MD, PhD, vice president of Research at Truveta Research Inc, launched the current research endeavor to compare on-treatment weight loss and rates of gastrointestinal adverse events among adults with overweight or obesity receiving tirzepatide or semaglutide labeled for type 2 diabetes in a clinical setting. To do so, investigators designed the study as retrospective, observational cohort study of adults with overweight or obesity considered new users of semaglutide or tirzepatide between May 2022 and September 2023 within the Truveta dataset, which aggregates electronic health record from a collective of US health care systems.1

For inclusion, patients needed to have overweight or have obesity and have a first dispensing oftirzepatide or semaglutide labeled for type 2 diabetes between May 1, 2022 and September 30, 2023. For the purpose of analysis, overweight and obesity were defined according to BMI definitions as well as diagnosis codes, with inclusion criteria requiring this to be recorded at least a year before their index date.1

The primary outcome of interest for the trial was the on-treatment weight change among the propensity score-matched groups, with a specific interest in the hazard ratio (HR) of achieving weight loss of 5% or greater, 10% or greater, and 15% or greater weight loss as well as the percentage change in weight at 3, 6, and 12 months. Propensity score-matching was performed using 1:1 nearest neighbor propensity score matching and statistical models used age, presence of type 2 diabetes, and baseline weight as covariates to control for residual confounding.1

Investigators identified a total of 41,222 adults meeting study criteria. Among this group, 32,029 received semaglutide and 9193 received tirzepatide. Of the 41,222 identified for possible inclusion, 18,386 remained after propensity score matching.1

The matched cohort had a mean baseline weight of 110 (SD, 25.8) kg, mean age of 52.0 (SD, 12.9) years, 70.5% were female, 77.1% were White, 11.8% were Black, 1.9% were Asian, and 52.0% had type 2 diabetes. Investigators pointed out follow-up was ended by discontinuation for 55.9% of those receiving tirzepatide and 52.5% of those receiving semaglutide.1

Upon analysis, results indicated those receiving tirzepatide were significantly more likely to achieve weight loss of 5% or greater (HR, 1.76, 95% CI, 1.68 to 1.84), 10% or greater (HR, 2.54; 95% CI, 2.37 to 2.73), and 15% or greater (HR, 3.24; 95% CI, 2.91 to 3.61) relative to their counterparts receiving semaglutide.1

Analysis of on-treatment changes with each agent revealed changes in weight were greater for those receiving semaglutide at the 3-month (difference, −2.4%; 95% CI, −2.5% to −2.2%), 6-month (difference, −4.3%; 95% CI, −4.7% to −4.0%), and 12-month (difference, −6.9%; 95% CI, −7.9% to −5.8%) timepoints. In analyses of drug safety and adverse events, there were no significant differences in gastrointestinal adverse events between the study groups.1

Investigators called attention to several limitations within the study to consider before overinterpretation of results. These limitations included reliance on electronic health record data, the possibility of underreporting for adverse events relative to protocoled, prospective trials, and reliance on brand as a proxy for target dose, among others.1

“Assessing the real-world effect of semaglutide and tirzepatide on weight loss provides a glimpse into what we may see with the recently approved obesity drug tirzepatide and how it might compare with semaglutide," said aid Tyler Gluckman, MD, MHA, a cardiologist at Providence Health and medical director at the Center for Cardiovascular Analytics, Research, and Data Science at the Providence Heart Institute.2 "Because tirzepatide was only approved by the FDA in mid-2022 for type 2 diabetes, the ability to rigorously analyze its use (on- and off-label) for a broad population of patients with overweight or obesity, not just a subset captured in insurance databases, has the power to greatly improve our understanding of how these agents are being used in every day practice and the effect that they’re having.”


  1. Rodriguez PJ, Goodwin Cartwright BM, Gratzl S, et al. Semaglutide vs Tirzepatide for Weight Loss in Adults With Overweight or Obesity. JAMA Intern Med. Published online July 08, 2024. doi:10.1001/jamainternmed.2024.2525
  2. Lampton E. Study comparing ozempic and Mounjaro published in Jama Internal Medicine. Truveta. July 8, 2024. Accessed July 8, 2024. https://www.truveta.com/blog/announcement/mounjaro-ozempic-weight-loss-jama-internal-medicine/.
  3. Campbell P. Semaglutide: The drug of today and a steppingstone to Tomorrow. HCP Live. December 6, 2023. Accessed July 8, 2024. https://www.hcplive.com/view/semaglutide-drug-today-steppingstone-tomorrow.
  4. Frías JP, Davies MJ, Rosenstock J, et al. Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes. N Engl J Med. 2021;385(6):503-515. doi:10.1056/NEJMoa2107519
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