Four GLP-1 drugs dominate the weight loss market in 2026: Wegovy (semaglutide), Zepbound (tirzepatide), Mounjaro (tirzepatide, approved for diabetes), and Ozempic (semaglutide, approved for diabetes but used off-label for weight loss). Here is what the clinical trials actually show.
How They Work
Semaglutide (Ozempic/Wegovy) is a GLP-1 receptor agonist. It mimics the GLP-1 hormone that targets areas of the brain that regulate appetite and food intake. Tirzepatide (Mounjaro/Zepbound) is a dual GIP and GLP-1 receptor agonist, targeting two metabolic pathways simultaneously.
Head-to-Head Trial Data
SURMOUNT-1 Trial (tirzepatide for obesity): Published in the New England Journal of Medicine (Jastreboff et al., 2022), this phase 3 trial enrolled 2,539 adults with obesity. At 72 weeks, participants lost an average of:
- 5 mg tirzepatide: 16.0% body weight (35 lbs)
- 10 mg tirzepatide: 21.4% body weight (49 lbs)
- 15 mg tirzepatide: 22.5% body weight (52 lbs)
- Placebo: 2.4% body weight (5 lbs)
Notably, 63% of participants on 15 mg lost at least 20% of their body weight, compared to just 1.3% on placebo (NEJM, 2022; 387:205-216). ClinicalTrials.gov ID: NCT04184622.
STEP 1 Trial (semaglutide for obesity): Published in NEJM (Wilding et al., 2021), this trial enrolled 1,961 adults. At 68 weeks:
- 2.4 mg semaglutide: 14.9% body weight (15.3 kg / 33.7 lbs)
- Placebo: 2.4% body weight
- 86.4% of semaglutide users lost at least 5% of body weight
- 50.5% lost at least 15%
- 32% lost at least 20%
ClinicalTrials.gov ID: NCT03548935.
Comparison Table
This would be a table showing: Drug | Active Ingredient | Approved For | Average Weight Loss (Trial) | Dosing |
| Drug | Ingredient | Approved For | Avg Weight Loss | Dosing |
|---|---|---|---|---|
| Ozempic | Semaglutide | Type 2 diabetes | ~12-15% | Weekly injection |
| Wegovy | Semaglutide | Weight loss | 14.9% at 68 wks | Weekly injection |
| Mounjaro | Tirzepatide | Type 2 diabetes | ~15-21% | Weekly injection |
| Zepbound | Tirzepatide | Weight loss | 20.9% at 72 wks | Weekly injection |
SURPASS-2: Tirzepatide vs Semaglutide Head-to-Head
The SURPASS-2 trial (Frias et al., The Lancet, 2021) directly compared tirzepatide against semaglutide in people with type 2 diabetes. Tirzepatide 10 mg and 15 mg were superior to semaglutide 1 mg for HbA1c reduction and weight loss. At 40 weeks, tirzepatide 15 mg led to 12.4 kg weight loss vs 7.9 kg for semaglutide 1 mg.
Which Should You Choose?
Tirzepatide-based drugs (Mounjaro/Zepbound) produce more weight loss on average. However, semaglutide-based drugs (Ozempic/Wegovy) have a longer safety track record and may be covered by more insurance plans. Cost and insurance coverage will likely be the deciding factor for most people.
References:
1. Jastreboff AM, et al. Tirzepatide Once Weekly for the Treatment of Obesity. NEJM 2022;387:205-216.
2. Wilding JPH, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity. NEJM 2021;384:989-1002.
3. Frias JP, et al. Tirzepatide versus semaglutide once weekly in patients with type 2 diabetes (SURPASS-2). The Lancet 2021;398:583-598.