Semaglutide vs tirzepatide: what the evidence says

How they work

Semaglutide and tirzepatide both act on the body's appetite and blood sugar hormones, but on a different number of receptors.

• Semaglutide is a GLP-1 receptor agonist. It is a GLP-1 analogue with 94% sequence homology to human GLP-1 (US semaglutide label). It is the active ingredient in Ozempic, Wegovy and Rybelsus.
• Tirzepatide activates two receptors, GIP and GLP-1, the targets of the body's own GIP and GLP-1 hormones (US Zepbound label). It is the active ingredient in Mounjaro and Zepbound.

Both lower calorie intake, and the US Wegovy and Zepbound labels say this is likely because they affect appetite. The Zepbound label adds that nonclinical studies suggest GIP may add to the regulation of food intake. Both raise insulin release and lower glucagon in a glucose-dependent manner, which lowers blood sugar in type 2 diabetes (US semaglutide and Mounjaro labels).

Both are long-acting: each binds to albumin, a blood protein, which prolongs its half-life (US labels). Both injections are given once a week. Wegovy tablets, an oral form of semaglutide in the US, are taken once a day.

Head-to-head trials

Two trials recorded here gave people either semaglutide or tirzepatide and compared the results directly. Both were open-label, meaning participants knew which medicine they were taking.

Doses in this table are the trial arms, not treatment advice.

SURMOUNT-5 was a phase 3b trial. Mean percent change in weight at week 72 was -20.2% (95% CI, -21.4 to -19.1) with tirzepatide and -13.7% (95% CI, -14.9 to -12.6) with semaglutide. The semaglutide doses used (1.7 or 2.4 mg) are the Wegovy maintenance doses on the US label.

SURPASS-2 measured blood sugar, not weight in people without diabetes. The semaglutide dose used (1 mg) is an Ozempic dose. In body weight, the estimated difference versus semaglutide was -1.9 kg, -3.6 kg and -5.5 kg for tirzepatide 5, 10 and 15 mg (P<0.001 for all comparisons).

These are findings from two trials, each in one population over one period. Trial results do not predict how any one person will respond.

Separate placebo trials side by side

Most of the evidence for each medicine comes from trials that compared it with placebo, not with the other medicine. The table puts them next to each other, but these are not head-to-head results. The trials had different participants, lengths, doses and lifestyle programs, so their numbers cannot be compared directly.

Reaching 5% weight loss or more. In STEP 1, 86.4% on semaglutide and 31.5% on placebo lost 5% or more. In SURMOUNT-1, 85%, 89% and 91% on tirzepatide 5, 10 and 15 mg did, versus 35% on placebo.

Longer follow-up. In SURMOUNT-1 participants with obesity and prediabetes, mean weight change at 176 weeks (about 3 years) was -12.3%, -18.7% and -19.7% with tirzepatide 5, 10 and 15 mg, versus -1.3% with placebo.

How fast each works and what happens after stopping

In trials, weight loss with both medicines began early and continued for more than a year of treatment, but much of it came back after the medicine was stopped.

How fast.

• Semaglutide: in STEP 1, weight loss occurred early and continued throughout the 68 weeks (EMA product information). In STEP 5, mean weight fell until week 68 and then reached a plateau.
• Tirzepatide: in a SURMOUNT-1 analysis of 1,545 people on tirzepatide who took at least 75% of their doses, 82% had lost 5% or more by week 12. Of the rest, 90% reached 5% by week 72. No source recorded here gives a week at which tirzepatide weight loss levels off.

After stopping. Three trials recorded here looked at what happens when treatment ends.

In the STEP 1 extension, most heart and metabolic improvements also moved back towards baseline, and the authors wrote that ongoing treatment appears to be needed to keep the improvements. In SURMOUNT-4, 89.5% of those who continued tirzepatide kept at least 80% of their earlier weight loss, versus 16.6% of those switched to placebo.

These trials had different designs and lengths, so their numbers cannot be compared directly.

Muscle and fat

Both US labels (Wegovy and Zepbound) say the medicine lowers body weight with greater fat mass loss than lean mass loss.

• Tirzepatide: in a SURMOUNT-1 body scan (DXA) substudy of 160 people, body weight fell by 21.3%, fat mass by 33.9% and lean mass by 10.9% at week 72 with tirzepatide. With placebo the figures were 5.3%, 8.2% and 2.6%. In both groups, about 75% of the weight lost was fat and 25% was lean mass.
• Semaglutide: in a STEP 1 DXA substudy of 140 people, the fall in fat mass was larger than the fall in lean mass after 68 weeks, and visceral (belly) fat also fell. The EMA says these results suggest most of the weight lost was fat tissue. The exact figures are not recorded here.
• Semaglutide in East Asian adults: in STEP 6, in 401 adults from Japan and South Korea with obesity, abdominal visceral fat area, measured by CT in a subset, fell by 40.0% with semaglutide 2.4 mg versus 6.9% with placebo over 68 weeks.

The two DXA substudies used different groups and reported results differently, so they cannot be compared directly.

Heart, kidney, sleep apnea and heart failure outcomes

Several large trials looked beyond weight. Some found fewer events, and some did not improve every measure.

What the US labels say.

• Heart: the US Wegovy label includes reducing the risk of major heart and blood vessel events in adults with established cardiovascular disease and obesity or overweight. The US Ozempic label includes this for adults with type 2 diabetes and established cardiovascular disease, and the US Mounjaro label for adults with type 2 diabetes at high risk.
• Kidney: the US Ozempic label includes reducing the risk of sustained eGFR decline, end-stage kidney disease and cardiovascular death in adults with type 2 diabetes and chronic kidney disease, and presents FLOW as the trial behind it. The Philippine package insert for Ozempic (linked from FDA Philippines Verification Portal record BR-1326) has no kidney indication. No tirzepatide kidney outcome trial is recorded on this page.
• Sleep apnea: the US Zepbound label includes moderate to severe obstructive sleep apnea in adults with obesity. No semaglutide sleep apnea trial is recorded on this page.
• Heart failure: the US Zepbound label (revised 08/2026) does not list a heart failure indication, although SUMMIT reported results in heart failure with preserved ejection fraction. Heart failure is not among the US Wegovy indications recorded here, although STEP-HFpEF reported results.

These trials enrolled different people and measured different outcomes, so they are not a comparison of the two medicines.

Side effects compared

The most common side effects of both medicines affect the stomach and gut.

The trial rows measured different things in different people, so the numbers cannot be compared directly. The head-to-head trials (SURMOUNT-5 and SURPASS-2) are recorded here for their main results only, not their side effect rates.

The Zepbound label says: "The majority of nausea, vomiting, and/or diarrhea events occurred during dose escalation and decreased over time." The STEP 1 authors described nausea and diarrhea as typically transient and mild to moderate.

Serious warnings compared

Both medicines carry a similar boxed warning and share most serious risks on their US labels (Wegovy and Ozempic for semaglutide, Zepbound and Mounjaro for tirzepatide).

Where they differ on the labels.

• Birth control pills: the US Zepbound label says tirzepatide may make them less effective, and advises a non-oral method or an added barrier method for 4 weeks after starting and for 4 weeks after each dose increase.
• Planning a pregnancy: the US Wegovy label advises stopping semaglutide at least 2 months before a planned pregnancy, because of its long half-life. The US Zepbound label advises stopping tirzepatide when a pregnancy is recognized.
• Other medicines taken by mouth: semaglutide delays stomach emptying and may affect how other oral medicines are absorbed (US Ozempic label).
• Combining: the US Wegovy label says using it with other semaglutide products or any other GLP-1 receptor agonist is not recommended. The US FDA says Zepbound should not be used with Mounjaro or a GLP-1 receptor agonist.

Dose schedules on the US labels

Both medicines start at a low weekly dose and are raised step by step. The labels say this is to reduce the risk of gastrointestinal side effects. These are the US label schedules for the branded medicines, not personal advice. Your doctor sets your dose.

The dose schedules in the Philippine package inserts are not recorded here, so these come from the US prescribing information. They are not schedules for compounded semaglutide or tirzepatide.

Both are injected under the skin once weekly, at any time of day, with or without meals. The Wegovy and Ozempic labels add "on the same day each week". The Wegovy label says to consider delaying a dose increase by 4 weeks if a dose is not tolerated. The Zepbound label says the 2.5 mg dose is for starting treatment and is not approved as a maintenance dose.

Branded, compounded and unregistered versions

Not every product sold as semaglutide or tirzepatide is the same. There are three kinds.

• Branded: Ozempic, Wegovy and Rybelsus (semaglutide), and Mounjaro and Zepbound (tirzepatide). The trial results and label facts on this page are for these medicines.
• Compounded: a compounded preparation made by a pharmacy. Compounded semaglutide is not the same product as Ozempic, Wegovy or Rybelsus. Compounded tirzepatide is not the same product as Mounjaro or Zepbound. The trial results on this page are not results for compounded versions.
• Unregistered or fake: products without registration, products labeled "for research purposes", and counterfeits.

What the US FDA says. These statements apply to the US legal framework, not the Philippines.

• Page current as of October 1, 2026: "compounded drugs are not FDA approved. This means the agency does not review compounded drugs for safety, effectiveness or quality before they are marketed." Compounded drugs "should only be used in patients whose medical needs cannot be met by an FDA-approved drug."
• Adverse event reports, as of May 31, 2026: 990 reports associated with compounded semaglutide, and "more than 730 reports of adverse events associated with compounded tirzepatide". The US FDA says both are likely underreported.
• Dosing errors: the US FDA has received reports, some requiring hospitalization, that may be linked to dosing errors with compounded injectable semaglutide, and reports that may be related to compounded semaglutide or tirzepatide prescribed in doses beyond the FDA-approved label.
• Fakes: the US FDA reports counterfeit Ozempic, fraudulent compounded semaglutide and tirzepatide with false labels, and products falsely labeled "for research purposes" or "not for human consumption".
• Shortages ended: the US FDA said the tirzepatide injection shortage was resolved on December 19, 2024, and the semaglutide injection shortage on February 21, 2025. On April 1, 2026 it said: "Tirzepatide and semaglutide do not currently appear on the 503B bulks list or on FDA's drug shortage list."

In the Philippines. FDA Philippines issued two advisories recorded here, No. 2026-0814 (July 30, 2026) and No. 2026-1020 (September 1, 2026), each warning the public not to buy or use an unregistered tirzepatide product that has no Certificate of Product Registration. No FDA Philippines advisory naming semaglutide was found, and no FDA Philippines statement specifically about compounded semaglutide or tirzepatide was found. Zuellig Pharma, the Philippine distributor of Mounjaro, has warned that illegally compounded tirzepatide poses significant health risks, including improper dosing and possible impurities and contamination (BusinessWorld, April 2026).

PH status compared

The table shows what the FDA Philippines Verification Portal listed for each brand when it was searched on October 7, 2026. The portal records show registration and prescription status. The approved uses come from the Philippine package inserts linked from those records, which apply to products registered in the Philippines.

Advisories. FDA Philippines has warned against two unregistered tirzepatide products (see above). No FDA Philippines advisory naming semaglutide, Ozempic, Wegovy or Rybelsus was found. In 2024, FDA Philippines said it was concerned about Ozempic being sold online without a prescription, was investigating online sellers, and asked the public to report illegal online sales to ereport@fda.gov.ph.

Prescriptions. Under the Philippine Pharmacy Act (RA 10918, Sections 30 and 33), prescription medicines may be dispensed only by a registered and licensed pharmacist with a valid prescription from a physician, dentist or veterinarian. Medicines may be sold to the public only through a retail drug outlet licensed by FDA Philippines. You can check a product's status on the FDA Philippines verification portal.

For more on each medicine, see semaglutide and tirzepatide.

How to choose

Whether either medicine suits you, and which one, is a decision for a licensed doctor who knows your health history. The sources on this page point to factors a doctor may weigh:

• Type 2 diabetes: Ozempic and Mounjaro are approved in the US for blood sugar control in type 2 diabetes, and Wegovy and Zepbound for weight management. SURPASS-2 compared the two in people with type 2 diabetes.
• Approved uses: the US labels differ. Wegovy includes heart risk reduction in people with cardiovascular disease, Ozempic includes kidney outcomes in type 2 diabetes with chronic kidney disease, and Zepbound includes obstructive sleep apnea with obesity. The Philippine package inserts differ from the US labels: Ozempic is for type 2 diabetes and, in three of its four inserts, heart risk reduction, with no weight or kidney indication, Wegovy is for weight management, and Mounjaro KwikPen is for type 2 diabetes and weight management.
• What is registered locally: Ozempic, Wegovy, Rybelsus, Mounjaro and Mounjaro KwikPen are listed as registered in the FDA Philippines Verification Portal (checked October 7, 2026). No record was found for Zepbound.
• Side effects and tolerance: both mainly cause stomach and gut side effects, and the labels raise the dose slowly to reduce them.
• Medical history: neither may be used with a personal or family history of MTC or MEN 2. Both labels warn about pancreatitis, gallbladder disease and diabetic retinopathy, and the Ozempic and Zepbound labels say they are not recommended with severe gastroparesis.
• Contraception and pregnancy plans: tirzepatide may make birth control pills less effective, and the Wegovy label advises stopping semaglutide at least 2 months before a planned pregnancy.
• Other medicines: insulin or a sulfonylurea raises the risk of low blood sugar with either medicine.
• Long-term plans: in trials, weight came back after either medicine was stopped.

Trial results describe groups of people, not what will happen to any one person.