Q&A: Factors Showing Tirzepatide is More Beneficial Than Semaglutide | ASHP Midyear

According to SURMOUNT-1 and SURMOUNT-2 trial research, the glucagon-like peptide-1 (GLP-1) tirzepatide showed significantly greater weight loss among patients with obesity who did and did not have type 2 diabetes (T2D) when compared with patients using semaglutide. Research data was presented at the American Society of Health-System Pharmacists (ASHP) 2024 Midyear Clinical Meeting.

“Recently, it has been approved for the management of moderate-to-severe obstructive sleep apnea. However, semaglutide has an indication for cardiovascular risk reduction whether used for people living with [T2D] or obesity. Tirzepatide’s cardiovascular evidence among people with [T2D] should be forthcoming in 2025, but it will be a few more years until evidence is reported on these outcomes in individuals living with obesity,” said Jennifer Clements, PharmD, BCACP, BC-ADM, BCPS, CDCES, FADCES, FCCP.

Mounjaro is just 1 example of an injectable version of a GLP-1 medication. | image credit: Cynthia / stock.adobe.com

Clements gave a presentation at ASHP Midyear 2024 titled “Let the Debate Begin: GLP-1 Receptor Agonists vs Newer Incretin Mimetics for Obesity and Type 2 Diabetes.” After the session, she caught up with Drug Topics to discuss the current indications of tirzepatide and semaglutide, who they compare to each other, and what to expect from each medication in the future.

Drug Topics: Can you discuss the data from the SURMOUNT clinical trials that demonstrate an edge for tirzepatide over semaglutide?

Jennifer Clements: The SURMOUNT-1 trial included adults with at least 1 unsuccessful dietary effort to lose weight. In addition, their weight was classified as overweight or obesity in the presence of a comorbidity (eg, hypertension, hyperlipidemia). SURMOUNT-1 trial investigated the efficacy and safety of tirzepatide among adults with [T2D] who were overweight or had obesity. Both trials had coprimary outcomes, which included percent change in body weight and achievement of 5% (or more) weight loss from baseline to week 72.

When looking at the results in SURMOUNT-1 trial, tirzepatide had statistically and clinically significant reduction versus placebo. The weight reduction was 15.9%, 19.5%, and 20.9% with tirzepatide 5 mg, 10 mg, and 15 mg, respectively. In addition, more than 85% of individuals achieved the 5% (or more) weight loss goal of 5%. It was more common for individuals to discontinue tirzepatide due to gastrointestinal reactions, which is consistent with other evidence with GLP-1 receptor agonists. From the SURMOUNT-2 trial, change in body weight was -12.8% and -14.7% with tirzepatide 10 mg and 15 mg, respectively, when compared [with] placebo. The percentage was not the same as SURMOUNT-1 trial given that there is insulin resistance among people with [T2D]. More than three-fourths of individuals achieved that minimum weight loss goal of 5% or more in the SURMOUNT-2 trial. Safety outcomes were consistent and similar with discontinuation due to gastrointestinal adverse events in the first couple of months in the SURMOUNT-2 trial.

When comparing semaglutide versus tirzepatide, tirzepatide has greater weight loss in those living with obesity with or without [T2D]. In addition, it has different cardiovascular outcomes among those with obesity and heart failure with preserved ejective fraction. Recently, it has been approved for the management of moderate-to-severe obstructive sleep apnea. However, semaglutide has an indication for cardiovascular risk reduction whether used for people living with [T2D] or obesity. Tirzepatide’s cardiovascular evidence among people with [T2D] should be forthcoming in 2025, but it will be a few more years until evidence is reported on these outcomes in individuals living with obesity. The person with [T2D] and other comorbid conditions will make the decision about what treatment is going to be best for them. Decisions will vary from person to person based on individual needs and preferences. In addition, there should be shared decision-making on the best agent for an individual when considering lifestyle habits, budget/financial restraints, and insurance coverage.

Follow along with our coverage of the 2024 ASHP Midyear Clinical Meeting and Exhibition here.