A new study published in JAMA Internal Medicine has found that tirzepatide outperforms the widely acclaimed semaglutide in facilitating substantial weight loss.
Overweight or obese individuals treated with tirzepatide, regardless of diabetes status, were significantly more likely to achieve at least 5%, 10%, and 15% body weight loss compared with those treated with semaglutide. There were no significant differences in gastrointestinal adverse events between tirzepatide and semaglutide.
Individuals without type 2 diabetes (T2D) had larger weight reductions than those with T2D in both groups, but tirzepatide was still associated with greater weight loss in all analyses.
This study represents the first clinical comparative effectiveness study of tirzepatide and semaglutide in overweight/obese adults.
Semaglutide vs tirzepatide
Semaglutide (Ozempic, Wegovy, Rybelsus) acts as a glucagon-like peptide-1 (GLP-1) receptor agonist, mimicking the body’s natural GLP-1 hormone. It binds to the GLP-1 receptor to produce its effects.
Tirzepatide (Mounjaro, Zepbound) is a dual-acting agonist, targeting both glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 receptors. It binds to both GIP and GLP-1 receptors. GIP, like GLP-1, is a natural incretin hormone that may enhance tirzepatide’s action.
The cohort study compared the effects of taking semaglutide (Ozempic, Novo Nordisk) and tirzepatide (Mounjaro, Eli Lilly) between May 2022 and September 2023. The study drew data from electronic health records of various US healthcare systems, ultimately including a sample size of 9,193 participants per treatment group after propensity score matching.
Approximately 52% of each group had a pre-existing diagnosis of T2D. The average duration of on-treatment follow-up spanned 165 days.
Of note, over half of the participants in both groups discontinued their respective treatments during the observation period. Specifically, 55.9% of individuals in the tirzepatide group and 52.5% in the semaglutide group ceased their prescribed regimens.
Tirzepatide tops semaglutide for weight loss
The study’s findings demonstrated the use of tirzepatide was associated with “significantly greater weight loss” than semaglutide. The proportions of individuals achieving at least 5%, 10%, and 15% weight loss within one year were strikingly higher in the tirzepatide group:
- 81.8% vs 66.5% achieved at least 5% weight loss
- 62.1% vs 37.1% achieved at least 10% weight loss
- 42.3% vs 18.1% achieved at least 15% weight loss
These results were further corroborated by hazard ratios calculated for each weight loss threshold. When comparing tirzepatide with semaglutide, the hazard ratios were:
- 1.76 (95% CI, 1.68-1.84) for achieving at least 5% weight loss
- 2.54 (95% CI, 2.37-2.73) for achieving at least 10% weight loss
- 3.24 (95% CI, 2.91-3.61) for achieving at least 15% weight loss.
After adjusting for potential residual confounding factors, the study quantified the absolute differences in weight loss between the two treatment groups at various time points. At 3, 6, and 12 months of treatment, the respective weight loss advantages favouring tirzepatide were:
- -2.4% (95% CI, -2.5% to -2.2%) at 3 months
- -4.3% (95% CI, -4.7% to -4.0%) at 6 months
- -6.9% (95% CI, -7.9% to -5.8%) at 12 months.
Study limitations
While the study’s findings are compelling, the author’s note the study has several limitations. These include include the potential for unmeasured confounding factors, reliance on electronic health record reporting and the use of brand names as proxies for dosing information.
Further, this study included medications labeled for T2D only. Future studies are needed to compare versions labeled for weight loss.
Also of note is that most patients in this study discontinued. Additional research on discontinuation is needed, including the role of shortages, adverse events and costs.
