Tirzepatide Bests Semaglutide for Real-World Weight Loss

In formulations indicated for type 2 diabetes, tirzepatide (Mounjaro) yielded more weight loss than semaglutide (Ozempic) in people with overweight or obesity, according to real-world data.

In the first 3 months on treatment, patients receiving tirzepatide lost 2.5% (95% CI -2.5% to -2.2%) more body weight than those on semaglutide, reported Nicholas Stucky, MD, PhD, of the health data collective Truveta in Bellevue, Washington, and colleagues.

Patients receiving tirzepatide continued to shed more weight than those on semaglutide up to a year, the group detailed in JAMA Internal Medicine:

• 6-month difference: -4.3% (95% CI -4.7% to -4.0%)
• 12-month difference: -6.9% (95% CI -7.9% to -5.8%)

“There has been evidence that these medications are effective for weight loss, but it hadn’t been clear just how effective they are, particularly in relation to each other,” co-author Tricia Rodriguez, PhD, MPH, also of Truveta, told MedPage Today. “While clinical trials don’t always generalize to the real-world, our findings were broadly consistent with placebo-controlled clinical trials, finding that the majority of patients on both medications experience clinically meaningful weight loss within a year on treatment.”

She explained that as head-to-head trials for patients with overweight or obesity are still months away at best, little real-world data exist to compare the effectiveness of the two most popular GLP-1 receptor agonist containing medications, which prompted her group to undertake this study.

“This study can help to inform patient care and outcomes today, not months from now,” she said.

Tirzepatide-treated patients were also 76% more likely to achieve at least a 5% weight loss — the threshold for clinical significance — than those on semaglutide (HR 1.76, 95% CI 1.68-1.84). They were also over two-fold and three-fold more likely to achieve at least a 10% and 15% total weight loss, respectively (HR 2.54, 95% CI 2.37-2.73, and HR 3.24, 95% CI 2.91-3.61).

Over the course of a year on treatment, average body weight loss was as follows:

• 3 months: 5.9% for tirzepatide vs 3.6% for semaglutide
• 6 months: 10.1% for tirzepatide vs 5.8% for semaglutide
• 12 months: 15.3% for tirzepatide vs 8.3% for semaglutide

Rates of moderate-to-severe gastrointestinal adverse events (the most commonly reported side events with GLP-1 receptor agonists) were similar between the two injectables. Discontinuation rates were high in both groups — 55.9% of patients on tirzepatide and 52.5% of patients on semaglutide — within 12 months.

The study cohort included 18,386 patients after propensity score matching from a subset of Truveta data using a de-identified electronic health record from a collective of U.S. health care systems. All patients had either overweight (BMI ≥27) or obesity (BMI ≥30) in the year before their index date.

They were new initiators on tirzepatide or semaglutide labeled for type 2 diabetes from May 1, 2022 (the month of tirzepatide approval), through September 30, 2023. For the type 2 diabetes indication, the standard full dose is 0.5 mg for semaglutide and 5.0 mg for tirzepatide.

At the time of the analysis, tirzepatide wasn’t yet approved for a chronic weight management indication, which it received in November 2023. A higher dosage of semaglutide (2.4 mg) was approved for weight management in June 2021 under the name Wegovy, but prescriptions for that weren’t included in the analysis.

About 52% of both groups had type 2 diabetes defined by a diagnosis, a prescription for insulin or a DPP-4 inhibitor, or an HbA1c level of 7.5% or greater in the 2 years before their index date. The average patient age was 52. Of the patients, 70.5% were female, 77.1% were white, and 43.3% lived in Texas.

Among the half of patients who had type 2 diabetes at baseline, they experienced less weight loss than those without diabetes. This finding was consistent with clinical trials.

“Although differential impacts on weight are possible, patients with and without type 2 diabetes may have differing motivation levels for weight loss and may engage in other weight loss activities differentially,” the researchers pointed out.

Because the analysis used electronic health record data, adverse events may have been underreported and patients in both groups may have received higher or lower doses than standard type 2 diabetes doses.

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