Head to Head Comparison of GLP-1 RAs for Weight Loss Tips Scales in Tirzepatide’s Favor

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Previously, data from head-to-head trials of tirzepatide and semaglutide were not available.

Tirzepatide is associated with significantly more weight loss than semaglutide in adults with overweight or obesity, according to results of a real-world study published in JAMA Internal Medicine.1

Investigators set out to compare both on-treatment weight loss and gastrointestinal adverse events in a cohort of adults who received either drug between May 2022 and September 2023.

The study cohort included new users of either medication with overweight or obesity, regardless of type 2 diabetes status or diagnosis. Researchers defined “new users” as individuals with no previous dispensation of any glucagon-like peptide-1 receptor agonist (GLP-1 RA) or GLP-1 RA/gastric inhibitory polypeptide (GIP) agonist labeled for type 2 diabetes (Ozempic and Mounjaro, respectively). A body mass index (BMI) threshold of 27 or higher was used to mirror patients with overweight or obesity in clinical trials.

Tirzepatide is more likely to lead to clinically meaningful weight loss compared with semaglutide. | Image credit: anatoliycherkas - stock.adobe.com

Tirzepatide is more likely to lead to clinically meaningful weight loss compared with semaglutide. | Image credit: anatoliycherkas - stock.adobe.com

The primary outcome was on-treatment weight loss; percentage change in body weight was calculated as (follow-up weight – baseline weight)/baseline weight. Safety outcomes included cases of moderate to severe gastrointestinal adverse events, including bowel obstruction, cholecystitis, cholelithiasis, gastroenteritis, gastroparesis, and pancreatitis, identified via electronic health record data.

A total of 41,222 patients met inclusion criteria: 9193 using tirzepatde and 32,029 using semaglutide. Before propensity score matching, patients in the tirzepatide group were younger and more likely to be White, college educated women. These patients also had a lower prevalence of type 2 diabetes and other comorbidities. Mean baseline weight was similar between groups (110±25.7 kg vs 109±25.2 kg, respectively).

READ MORE: Ozempic, Other GLP-1 Therapies Caused Major Increase in Medicare Spending

Mean duration of on-treatment follow-up was 165 days (median, 129 days; IQR, 75-231 days; difference, 156 days). Overall, follow-up was ended by treatment discontinuation in 54.2% of patients, medication switching in 0.8% of patients, and administrative censoring for 45% of patients.

Within the propensity matched population, 81.8% of patients receiving tirzepatide achieved 5% or greater weight loss; 37.1% achieved 10% or greater weight loss, and 42.3% achieved 15% or greater weight loss within 1 year (vs 66.5%, 37.1%, and 18.1% in the semaglutide group, respectively). Hazard ratios comparing the two medications were 1.76 for 5% or greater weight loss, 2.54 for 10% or greater weight loss, and 3.25 for 15% or greater weight loss.

Patients in the tirzepatide group also experienced a higher mean on-treatment change in body weight vs semaglutide: -5.9% vs -3.6% at 3 months, -10.1% vs -5.8% at 6 months, and -15.3% vs -8.3% at 12 months. After adjustment for residual confounding, absolute difference in weight loss between both groups at 3, 6, and 12 months of treatment was -2.4%, -4.3%, and -6.9%, respectively.

No significant between-group differences in the risk of gastrointestinal adverse events were noted.

“To our knowledge, this study represents the first clinical comparative effectiveness study of tirzepatide and semaglutide in adults with overweight or obesity,” the researchers noted, adding that “findings in this study are broadly consistent with existing evidence from [randomized controlled trials].” Data from head-to-head studies are more limited; the SURMOUNT-5 clinical trial (NCT05822830), comparing tirzepatide to semaglutide in adults with overweight or obesity, but without type 2 diabetes, is underway with results expected in late 2024.

Study limitations included the potential for informative censoring due to the directly observable nature of weight loss to patients, the use of clinical electronic health record data, a potential lack of underreported adverse events, the use of medications labeled for type 2 diabetes, rather than for weight loss, and the potential lack of generalizability to the broader US.

READ MORE: Study Reveals Robust Benefits of Semaglutide in Protecting Against Kidney, CV Events in Patients With T2D

“Individuals with overweight or obesity treated with tirzepatide were significantly more likely to achieve clinically meaningful weight loss and larger reductions in body weight compared with those treated with semaglutide,” the researchers concluded. “Future work is needed to compare the effect of tirzepatide and semaglutide on other key endpoints” such as the reduction in major adverse cardiovascular events.

Reference
Rodriguez PJ, Cartwright BMG, Gratzl S, et al. Semaglutide vs tirzepatide for weight loss in adults with overweight or obesity. JAMA Intern Med. Published online July 8, 2024. doi:10.1001/jamainternmed.2024-2525
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