Semaglutide is the drug in Ozempic, Wegovy and the semaglutide pills, made by Novo Nordisk. Tirzepatide is the drug in Zepbound and Mounjaro, made by Eli Lilly. They're the two most prescribed weekly GLP-1 drugs, and two direct trials have compared them. The brand pages go deeper on each product; this page stays at the level of the two molecules. Start with the semaglutide guide or the tirzepatide guide for either drug on its own.
The core difference: one receptor or two
Both drugs copy gut hormones your body releases after eating. Semaglutide copies GLP-1, which slows the stomach, signals fullness to the brain and helps the pancreas release insulin when blood sugar rises. Tirzepatide copies GLP-1 too, and also GIP, a second gut hormone involved in insulin release and fat storage.
That second receptor is the main design difference, and it's the likeliest reason tirzepatide produced more weight loss in trials. It doesn't make the side effects very different: both drugs mostly cause nausea, diarrhea, vomiting and constipation, especially while the dose is being raised.
Weight loss head to head: tirzepatide lost more in SURMOUNT-5
SURMOUNT-5 randomized 751 adults with obesity and no type 2 diabetes to the highest dose each person tolerated: tirzepatide 10 or 15 mg, or semaglutide 1.7 or 2.4 mg, weekly for 72 weeks. Average weight loss was 20.2% on tirzepatide and 13.7% on semaglutide. Waist size fell by 7.2 inches (18.4 cm) against 5.1 inches (13.0 cm) [1].
Two things to keep in mind. Eli Lilly, which makes tirzepatide, funded the trial, and it was open-label, so people knew which drug they were on. And the semaglutide dose tested topped out at 2.4 mg. Wegovy's label added a 7.2 mg dose on March 19, 2026, and no head-to-head trial has tested that dose against tirzepatide.
The placebo-controlled trials point the same way. In STEP 1, semaglutide 2.4 mg produced 14.9% average weight loss at 68 weeks [3]. In SURMOUNT-1, tirzepatide's top dose produced 20.9% at 72 weeks [4]. Those were separate trials, so they back up SURMOUNT-5 rather than replace it. The weight-labeled brands are compared directly in Zepbound vs Wegovy.
Blood sugar head to head: tirzepatide lowered A1C more
SURPASS-2 compared the two in 1,879 adults with type 2 diabetes already taking metformin. Over 40 weeks, A1C, the three-month blood sugar average, fell by 2.01, 2.24 and 2.30 points on tirzepatide 5, 10 and 15 mg, against 1.86 points on semaglutide 1 mg. Weight loss was also greater with tirzepatide, by 4.2 to 12.1 pounds (1.9 to 5.5 kg) depending on dose [2]. Eli Lilly funded this trial too.
The semaglutide dose in SURPASS-2 was 1 mg, below Ozempic's current 2 mg label maximum. The diabetes brands are compared in full in Ozempic vs Mounjaro.
Beyond weight, semaglutide has more proven outcomes
Weight and blood sugar are what people notice. What a drug has proven about heart attacks, kidneys and the liver matters more for the long run, and this is where the two molecules differ most.
| Semaglutide | Tirzepatide | |
|---|---|---|
| Receptors | GLP-1 | GIP and GLP-1 |
| Weekly weight trial vs placebo | STEP 1: −14.9% at 68 weeks | SURMOUNT-1: −20.9% at 72 weeks (top dose) |
| Head to head, obesity (SURMOUNT-5) | −13.7% | −20.2% |
| Head to head, type 2 diabetes (SURPASS-2) | A1C −1.86 points (1 mg) | A1C −2.01 to −2.30 points |
| Labeled heart-risk reduction | Wegovy: adults with heart disease and obesity or overweight (2024). Ozempic: type 2 diabetes with heart disease | Mounjaro: adults with type 2 diabetes at high heart risk (2026) |
| Labeled kidney outcome | Ozempic: type 2 diabetes with chronic kidney disease (2025) | None |
| Labeled sleep apnea | None | Zepbound: moderate to severe sleep apnea with obesity (2024) |
| Labeled MASH liver disease | Wegovy, accelerated approval (2025) | None |
| Teens | Wegovy: 12 and older | Mounjaro: 10 and older (type 2 diabetes only) |
| Trial funders | Novo Nordisk (STEP 1, SELECT, FLOW, SUSTAIN-6, ESSENCE) | Eli Lilly (SURMOUNT-1, SURMOUNT-5, SURPASS-2, SURPASS-CVOT) |
STEP 1 [3]; SURMOUNT-1 [4]; SURMOUNT-5 [1]; SURPASS-2 [2]; labels: Wegovy [11], Ozempic [12], Zepbound [13], Mounjaro [14].
- Heart. SELECT enrolled 17,604 adults with heart disease and overweight but no diabetes; semaglutide cut heart attacks, strokes and heart deaths by 20% (hazard ratio 0.80) [5]. SUSTAIN-6 showed a similar benefit in type 2 diabetes (hazard ratio 0.74) [6]. Tirzepatide's heart trial, SURPASS-CVOT, compared it with another GLP-1 drug rather than placebo: 12.2% against 13.1% had a major heart event, which showed it was no worse [10].
- Kidneys. In FLOW, semaglutide 1 mg lowered major kidney events by 24% in type 2 diabetes with chronic kidney disease [7].
- Liver. In ESSENCE, 62.9% of people with MASH on semaglutide saw the liver inflammation resolve at 72 weeks, against 34.3% on placebo [8]. The approval is accelerated, so liver outcomes are still being tested.
- Sleep apnea. In SURMOUNT-OSA, tirzepatide cut breathing interruptions during sleep by about 20 to 24 more events an hour than placebo [9]. That's tirzepatide's distinct outcome.
Side effects are similar for both, and mostly digestive
In SURPASS-2, nausea hit 17% to 22% of people on tirzepatide and 18% on semaglutide; diarrhea 13% to 16% against 12%. Serious adverse events were 5% to 7% on tirzepatide and 3% on semaglutide [2]. In SURMOUNT-5, digestive effects were the most common in both groups, mostly mild to moderate, and showed up mainly while the dose was being raised [1].
Both drugs carry the same boxed warning about thyroid C-cell tumors seen in rodents, and the same class warnings about pancreatitis, gallbladder disease and kidney injury from dehydration [11] [13]. Neither is clearly gentler. Which one you tolerate better is something you and your prescriber find out.
Is tirzepatide the same as Ozempic? No
Ozempic is semaglutide. Tirzepatide is a different molecule from a different company, sold as Mounjaro and Zepbound. The diabetes brands, Ozempic and Mounjaro, are compared in Ozempic vs Mounjaro. If you're comparing Ozempic with the weight-loss brand, Ozempic vs Zepbound shows which pairs are like for like, and Wegovy vs Mounjaro covers the remaining cross pair.
Products, forms and cost: only semaglutide comes as a pill
| Product | Molecule | Form | Self-pay from the maker |
|---|---|---|---|
| Wegovy pen | Semaglutide | Weekly injection | $199 for each of the first 2 fills (new patients, through December 31, 2026), then $349; Wegovy HD 7.2 mg $399 |
| Wegovy pill | Semaglutide | Daily tablet | $149 to $299 by strength |
| Ozempic pen | Semaglutide | Weekly injection | $199 for each of the first 2 fills (new patients, through December 31, 2026), then $349 up to 1 mg, $499 at 2 mg |
| Ozempic pill | Semaglutide | Daily tablet | From $149 (1.5 mg) |
| Zepbound | Tirzepatide | Weekly injection (vial or KwikPen) | $299 to $449 with refills within 45 days |
| Mounjaro | Tirzepatide | Weekly injection | $499 at every strength |
NovoCare [15] [16] and LillyDirect [17] [18] self-pay pages. Prices per month.
Both molecules are also sold in compounded versions through telehealth, where cash prices run $75–$349 a month for semaglutide and $85–$399 for tirzepatide. Compounded drugs aren't FDA-approved, and FDA doesn't review them for safety, effectiveness or quality before they're sold. The compounded semaglutide guide and compounded tirzepatide guide explain what that means; the compounded semaglutide board and compounded tirzepatide board score the providers.
For the pill route, the semaglutide pill guide covers the Wegovy pill and Ozempic tablets. And if you've seen retatrutide mentioned as the next step up, it's still investigational and not FDA-approved; the retatrutide vs tirzepatide page covers its status.
Which one fits depends on the result you need
Since neither molecule wins everything, it helps to start from your own situation. These are the label and trial facts that usually decide the conversation with a prescriber:
- The most weight loss is the goal. Tirzepatide has the head-to-head result in SURMOUNT-5. Ask about Zepbound.
- You have heart disease and obesity or overweight. Wegovy carries the labeled heart-risk reduction, based on SELECT. Ask about Wegovy.
- You have type 2 diabetes and chronic kidney disease. Ozempic carries the kidney indication from FLOW. Ask about Ozempic.
- You have moderate to severe sleep apnea with obesity. Zepbound is the drug labeled for it.
- You'd rather not inject. Only semaglutide comes as a pill, though Foundayo, a different GLP-1 molecule, is another daily-tablet option.
- Cash price matters most. From 1 mg up, Wegovy is $349 a month; from 7.5 mg up, Zepbound is $449 with on-time refills. The table above has every tier.
Switching from one to the other is a prescriber decision
People switch for many reasons: side effects, a plateau, a coverage change or a new diagnosis. The doses don't convert one to one between molecules, so your prescriber sets the new starting point. Don't overlap them: both the Wegovy and Zepbound labels say combining with another GLP-1 drug "is not recommended" [11] [13].