Semaglutide vs. tirzepatide: weight loss, risks, and product differences

Who took part in the weight-loss study?

The study was called SURMOUNT-5. It assigned 751 adults to groups by chance, and 750 entered the main benefit and safety reviews. Each person used the highest study amount they could tolerate. People and researchers knew which medicine was used, a design called open-label. Eli Lilly, the tirzepatide maker, funded it.

The study compared the injections used in Zepbound and Wegovy. It did not test oral Wegovy, Wegovy HD, or compounded products. It also did not compare heart events, death, sleep apnea, kidney disease, or liver results. A larger average weight loss does not show which medicine suits one person.

What side effects and serious risks matter?

Stomach and bowel problems were the most common side effects in SURMOUNT-5. They occurred mainly while the study amount increased. Both medicines also carry serious warnings. The study does not show one safer choice for everyone.

Wegovy and Zepbound have boxed warnings about thyroid C-cell tumors found in rodents. A boxed warning is FDA's strongest warning. It is not known whether this risk applies to people.

Both labels say not to use the product with a personal or family history of medullary thyroid cancer. They give the same warning for Multiple Endocrine Neoplasia syndrome type 2, a rare inherited condition. Neither medicine has been shown to cause these tumors in people, and the boxed warnings state that the human risk is unknown.

The two labels also share several warning groups. A shared warning does not mean every person will have these problems, or that both products carry the same level of risk.

Both labels warn about stomach and bowel reactions, which can be severe. They also warn about sudden pancreas inflammation, gallbladder disease, and sudden kidney injury linked to fluid loss. Other warnings cover serious allergic reactions and low blood sugar with some medicine combinations.

For people with type 2 diabetes, the labels discuss diabetic retinopathy, which is eye damage from diabetes. They also report pulmonary aspiration during deep sedation or general anesthesia. This means stomach contents entered the lungs.

Some warnings differ. Wegovy's label includes an increase in heart rate. Zepbound's label says slower stomach emptying can affect birth-control pills when treatment starts and when the amount increases. The labels also differ for pregnancy, breastfeeding, medicines taken by mouth, device use, and product forms.

In January 2026, FDA said its review found no increased risk of suicidal thoughts or actions. It asked makers to remove that warning from GLP-1 weight-management drug labels. Wegovy recorded the removal in January, and Zepbound recorded it in February.

Comparisons written earlier can therefore be out of date. Check the revision date on the current label.

The record fits neither “same class, same risk” nor “more weight loss, more danger.” Study rates can change with time on a medicine, planned increases, definitions, follow-up, and who could join. A clinician must review reasons not to use a product and other medicines. The review must also cover past reactions, diabetic eye disease, anesthesia plans, pregnancy, and stomach or bowel disease.

The product form can change the comparison.

Zepbound and Mounjaro are FDA-approved injections, with pens and vials among their product forms. Ozempic is also an injection, and its forms and device instructions differ from Wegovy's. Wegovy includes single-dose injections and a tablet for defined adult uses.

Wegovy HD is another Wegovy injection form for certain adults. Rybelsus and Ozempic tablets are oral semaglutide products for diabetes. Their label instructions affect how the body absorbs them.

The labels involve more than a choice of “pill versus shot.” Oral semaglutide labels have rules about timing, water, food, and other medicines. Injection labels have product-specific rules for handling and storage.

People cannot convert between brands or forms by matching milligrams. The current oral diabetes label says Rybelsus and Ozempic tablets are not equal milligram for milligram.

The article gives no instructions for starting, increasing, missing, switching, or injecting a medicine. These details differ by product and can change. Use the current FDA label and ask the pharmacist about the exact prescribed form.

A fair comparison names the brand, approved use, route, and current label. A route is how a medicine enters the body.

Access and cost depend on the exact product.

There is no single “semaglutide cost” or “tirzepatide cost.” A price needs the exact product name and a statement of what it includes. An online price can be a maker's list price, a pharmacy cash price, or a short-term savings price. It can also be an insurance copay or a clinic package with services and a different product.

Each of these prices measures something different. Coverage can depend on the exact FDA-approved brand and approved use. It can also depend on age, diagnosis, plan year, the plan's drug list, approval rules, and pharmacy network.

A current comparison starts with the prescribed product and approved use. The insurer or benefits manager, the pharmacy, and the maker's official program rules then give the price terms. A clinic price can include the FDA-approved product, visits, lab work, supplies, and follow-up, and it may change during care. A low monthly price without a product name is an incomplete comparison.

Do not place compounded semaglutide or tirzepatide in the same evidence group as Wegovy, Ozempic, Rybelsus, Zepbound, or Mounjaro. FDA does not review compounded drugs for safety, effectiveness, or quality before marketing. FDA has reported errors in the amount given, false labels, and health problems reported after use. It has also found semaglutide salt forms that differ from the active ingredient in approved drugs.

A compounder's use of the molecule name does not establish equivalence to the approved product studied in a trial.

• Confirm the exact FDA-approved brand and route, beyond the ingredient name.
• Match the wanted result to an approved use or a clearly limited study result.
• Read the current boxed warning, reasons not to use the product, major warnings, and medicine interactions.
• Check whether the study group matches the person in question. Important details include diabetes, age, heart disease, sleep apnea, kidney disease, and liver disease. Metabolic dysfunction-associated steatohepatitis (MASH) is a form of liver disease involving fat and inflammation.
• Check current coverage and total cost with the health plan and pharmacy. A price in search results does not promise a benefit.

How do the medicines work?

Semaglutide acts like GLP-1, a body signal that helps control blood sugar and appetite. Tirzepatide acts like GIP, another body signal, and like GLP-1. Both medicines affect food intake and how fast the stomach empties.

These effects help explain how the medicines work. They cannot predict one person's result.

FDA has approved several different products.

One ingredient can appear in several approved products. Each comparison must name the product because approved uses, benefits, warnings, and coverage can differ.

• Wegovy injection contains semaglutide under FDA application 215256. Its label covers long-term weight reduction in defined adults and teens. It also covers lower heart risk in defined adults with heart disease and overweight or obesity. Under accelerated approval, it covers noncirrhotic MASH with F2 to F3 liver scarring in defined adults.
• Wegovy tablets contain semaglutide under separate FDA application 218316. Their label covers long-term weight reduction and lower heart risk in defined adults. It does not cover teens or MASH. The tablets also have instructions for use by mouth.
• Wegovy HD is the 7.2 mg form within Wegovy injection's FDA application 215256. FDA approved it in March 2026 for long-term weight reduction in certain adults. SURMOUNT-5 did not study it.
• Ozempic injection contains semaglutide under FDA application 209637. Its label covers blood-sugar control and defined heart and kidney outcomes in adults with type 2 diabetes. SURMOUNT-5 did not use Ozempic as the semaglutide obesity product.
• Rybelsus and Ozempic tablets contain oral semaglutide under FDA application 213051. Their label covers blood-sugar control and lower risk of major heart events in defined adults with type 2 diabetes. The tablets are not equal milligram for milligram.
• Zepbound contains injectable tirzepatide under FDA application 217806. Its label covers long-term weight reduction in defined adults. It also covers moderate-to-severe obstructive sleep apnea in adults with obesity.
• Mounjaro contains injectable tirzepatide under FDA application 215866. Its August 2026 label covers blood-sugar control in adults and children age 10 or older with type 2 diabetes. It also covers lower risk of cardiovascular death, nonfatal heart attack, and nonfatal stroke in high-risk adults with type 2 diabetes. Cardiovascular death means death from heart or blood-vessel disease. These uses apply to Mounjaro; Zepbound has a separate label.

A benefit on one label does not apply to every product.

FDA approves exact products for exact uses. Wegovy injection's heart use applies to adults who have heart disease and overweight or obesity. Its MASH use covers defined adults with noncirrhotic F2 to F3 liver disease.

Noncirrhotic means that cirrhosis has not developed. This use has accelerated approval based on better liver tissue under a microscope, and proof of a clinical benefit is still required. These uses do not transfer to Ozempic, oral semaglutide, or a generic “semaglutide peptide.”

Zepbound's sleep-apnea use covers adults with obesity and moderate-to-severe obstructive sleep apnea. It does not cover every sleep problem, and it does not transfer to Mounjaro.

Ozempic injection covers blood-sugar control and defined heart and kidney outcomes in adults with type 2 diabetes. Rybelsus and Ozempic tablets cover blood-sugar and heart outcomes in defined adults with diabetes. These labels answer specific health questions. They do not rank products for online buyers.

How were the weight-loss results calculated?

The main result measured the change in body weight as a percentage of starting weight. Researchers used a planned method called the modified treatment-regimen estimand. It sets the rules for comparing groups, including people who stopped treatment early or used another obesity medicine.

The method had separate rules for people who switched to the other medicine or had surgery. The estimated difference in weight change was −6.5 percentage points. Its 95% confidence interval was −8.1 to −4.9. This range shows the uncertainty around the estimated difference. Average waist change also favored tirzepatide.

Eli Lilly helped with the study and data. Knowing which medicine was used could affect how people and researchers behaved. The results apply to this study plan and this group of participants.

The diabetes comparison answered a different question.

SURPASS-2 compared tirzepatide with semaglutide in 1,879 adults with type 2 diabetes. Metformin alone had not controlled their blood sugar well enough. The 40-week, open-label study assigned people to groups by chance.

It compared three set tirzepatide plans with one injectable semaglutide plan. The main result was glycated hemoglobin, or A1C, a measure of average blood sugar. Long-term weight control was a separate question.

All three tirzepatide groups lowered A1C at least as much as, and more than, the semaglutide group. This met the study's rules for being no worse and for being better. The tirzepatide groups also had larger average weight reductions. Stomach and bowel side effects were common in both groups.

SURPASS-2 was open label and supported by Eli Lilly. The study devices and planned increases in the medicine amounts prevented full masking. Its 40-week length left only 16 weeks after medicine levels became steady in the highest tirzepatide group. It did not compare tirzepatide with Wegovy's current weight-loss injection plan, oral Wegovy, or Wegovy HD.

The study did not test Zepbound's sleep-apnea use. It also did not test Wegovy's heart or MASH uses. Together, SURPASS-2 and SURMOUNT-5 provide direct comparisons in two health settings. They do not show that one ingredient is best for every result or person.