Tirzepatide 10 and 15 mg compared with semaglutide 2.4 mg for the treatment of obesity: An indirect treatment comparison

Abstract

Aim: To compare the efficacy of tirzepatide 10 and 15 mg with semaglutide 2.4 mg using an indirect treatment comparison.Materials and Methods: Using SURMOUNT-1 and STEP 1 trial data, mean percentage change in body weight from baseline and odds ratio (OR) of achieving 5% or greater weight loss were compared between tirzepatide 10 and 15 mg at week 72 and semaglutide 2.4 mg at week 68 using matching-adjusted indirect comparison of the efficacy estimand. Sensitivity analyses were completed using different methods, including the Bucher method, also using different estimands and/or time points.Results: Greater reductions in percentage change in body weight were observed with tirzepatide 10 and 15 mg versus semaglutide 2.4 mg (tirzepatide 10 mg mean difference: À4.67% [95% CI À5.91%, À3.43%]; tirzepatide 15 mg mean difference: À5.92% [95% CI À7.16%, À4.68%]; both P < .001). Similarly, more participants achieved 5% or greater weight loss with tirzepatide 10 mg (OR 2.61 [95% CI 1.48,4.57]; P < .001) and 15 mg (OR 2.75 [95% CI 1.57, 4.81]; P < .001) compared with semaglutide 2.4 mg. All sensitivity analyses were consistent, except for an OR of achieving 5% or greater weight loss with tirzepatide 10 mg using the Bucher method to analyse the treatment regimen estimand (P = .074).Conclusions: Currently there are no direct comparisons of tirzepatide and semaglutide for weight management. Using the matching-adjusted indirect treatment comparison method to compare the efficacy of tirzepatide and semaglutide for chronic weight management, this analysis showed greater weight loss with tirzepatide 10 and 15 mg versus semaglutide 2.4 mg.

Medications for Obesity

“…Similar to semaglutide, tirzepatide should be prescribed to adults needing to achieve greater weight reductions, particularly patients with greater weight-related morbidity (Table 2). Although there are no direct comparisons, tirzepatide 10 mg and 15 mg showed greater weight loss than semaglutide 2.4 mg …”

Effectiveness and safety of drugs for obesity

“…Phentermine-topiramate and naltrexone-bupropion had the highest risk of adverse events leading to discontinuation. A recent analysis of SURMOUNT-1 and STEP 1 trial data concluded that tirzepatide was likely more effective than semaglutide 140…”

“…A recent analysis of SURMOUNT-1 and STEP 1 trial data concluded that tirzepatide was likely more effective than semaglutide. 140 Real world comparative effectiveness data We found insufficient data from observational comparative effectiveness research designs to understand the real world treatment effectiveness and safety of antiobesity medications. 80 More research is needed to help inform treatment decisions in populations that are not typically included in clinical trials, such as those with multiple comorbidities and advanced age.…”

Role of lifestyle and glucagon‐like peptide‐1 receptor agonists for weight loss in obesity, type 2 diabetes and steatotic liver diseases

“…and liver-related outcomes are discussed extensively in recent reviews. 159,177,250,251 Briefly, once-weekly tirzepatide, a dual GIP/GLP-1R agonist, also shows high efficacy on weight reduction [252][253][254][255] but outcome studies are currently lacking. Dual glucagon receptor (GCGR)/GLP-1R agonists such as mazdutide (IBI362, LY3305677) achieved up to 6.4% weight loss at doses up to 6 mg once weekly in a phase Ib in Chinese adults.…”