Two Drugs. Different Mechanisms. Both Deliver Serious Results.
Ozempic (semaglutide) and Mounjaro (tirzepatide) are the two biggest names in the GLP-1 weight loss revolution. Both produce weight loss that was previously achievable only through bariatric surgery. But they’re not the same drug, and the differences matter more than most articles let on.
Let’s cut through the marketing and look at what the clinical trial data actually shows.
How They Work: One Receptor vs. Two
Ozempic/Wegovy (semaglutide) targets the GLP-1 receptor. GLP-1 is a hormone your gut releases after eating that tells your brain you’re full, slows stomach emptying, and improves insulin sensitivity. Semaglutide mimics this hormone but lasts much longer than the natural version.
Mounjaro/Zepbound (tirzepatide) targets two receptors: GLP-1 and GIP (glucose-dependent insulinotropic polypeptide). This dual mechanism is why researchers call it a “twincretin.” The GIP component adds effects on fat metabolism, energy expenditure, and appetite that go beyond what GLP-1 alone provides.
More receptors doesn’t automatically mean better — but in this case, the clinical trial results suggest it does produce somewhat greater weight loss.
Weight Loss: Head-to-Head Numbers
The most relevant clinical trial data:
Semaglutide (STEP trials):
- STEP 1 (2.4 mg weekly): 14.9% average body weight loss over 68 weeks
- About one-third of participants lost 20% or more of their body weight
- Placebo group lost 2.4%
Tirzepatide (SURMOUNT trials):
- SURMOUNT-1 (highest dose, 15 mg weekly): 20.9% average body weight loss over 72 weeks
- Over half of participants at the highest dose lost 20% or more
- At the 10 mg dose: 19.5% average loss
- At the 5 mg dose: 15.0% average loss
- Placebo group lost 3.1%
In practical terms: on Ozempic/Wegovy, a 250-pound person might lose about 37 pounds. On Mounjaro/Zepbound at the highest dose, that same person might lose about 52 pounds. That’s a meaningful difference.
Side Effects Comparison
Both drugs share the same primary side effects because they both activate GLP-1. But the rates and severity differ:
Nausea: Semaglutide — ~44%. Tirzepatide — ~28-31%. Mounjaro generally causes less nausea, which matters a lot for adherence.
Vomiting: Semaglutide — ~24%. Tirzepatide — ~12-17%.
Diarrhea: Semaglutide — ~30%. Tirzepatide — ~17-23%.
Constipation: Semaglutide — ~24%. Tirzepatide — ~17-24%.
Most GI side effects peak during dose escalation and settle within 4–8 weeks at each dose level. Slow titration helps. Some people tolerate one drug much better than the other for reasons that aren’t fully understood.
Serious but rare risks for both: pancreatitis (less than 1%), gallbladder problems (increased risk with rapid weight loss), and thyroid C-cell tumors (seen in rodent studies; relevance to humans uncertain but both carry a boxed warning).
Beyond Weight Loss: Other Health Benefits
Cardiovascular: Semaglutide has proven cardiovascular benefit. The SELECT trial showed a 20% reduction in major cardiovascular events in people with obesity but without diabetes. Tirzepatide’s cardiovascular outcomes trial (SURPASS-CVOT) is still ongoing.
Diabetes: Both are outstanding for type 2 diabetes management. Tirzepatide has shown superior A1C reduction in head-to-head studies against semaglutide (SURPASS-2 trial: tirzepatide reduced A1C by 2.0-2.3% vs. semaglutide’s 1.9%).
Blood pressure: Both reduce systolic blood pressure by 4–7 mmHg on average. Our blood pressure calculator can help you track your numbers.
Cost and Access
Without insurance, both drugs are expensive: roughly $900–$1,350 per month for Wegovy and $1,000–$1,200 for Zepbound. Insurance coverage varies wildly. Many plans cover them for diabetes but not for weight loss alone. Manufacturer savings programs exist but change frequently.
Supply has been an issue for both drugs since 2023, though availability has improved. Compounded versions exist but are controversial regarding quality, safety, and legality.
Which One Should You Choose?
There’s no universal “better” choice. Factors to consider:
- If maximizing weight loss is the primary goal, tirzepatide has a slight edge based on clinical trial data
- If you have established cardiovascular disease, semaglutide has proven heart benefits (tirzepatide’s trial is pending)
- If GI side effects concern you, tirzepatide may be better tolerated
- If you have type 2 diabetes and want the best A1C control, tirzepatide has a slight advantage
- Cost and insurance coverage may ultimately be the deciding factor for many people
Frequently Asked Questions
Can I switch from Ozempic to Mounjaro?
Yes, with your prescriber’s guidance. There’s no mandatory washout period. Most clinicians start tirzepatide at the lowest dose (2.5 mg) regardless of what semaglutide dose you were on, then titrate up based on tolerability and response.
Do you regain weight when you stop either drug?
Unfortunately, yes. The STEP 1 extension trial showed participants regained about two-thirds of lost weight within one year of stopping semaglutide. Similar patterns are expected with tirzepatide. These drugs manage obesity the way blood pressure medication manages hypertension — they work while you take them.
Can you take both drugs at the same time?
No. They share overlapping mechanisms and combining them would dramatically increase side effect risk, particularly severe GI symptoms and potential hypoglycemia. You take one or the other.
