Is Tirzepatide or Semaglutide Better for Weight Loss?

Tirzepatide produces more weight loss than semaglutide on average. In a 72-week trial that randomly gave adults with obesity (and without diabetes) one drug or the other, people on tirzepatide lost 20.2% of their body weight and people on semaglutide lost 13.7% (SURMOUNT-5 head-to-head trial). Semaglutide still works well, and it costs less at brand cash prices. Tirzepatide's advantage is clearest when your goal is to lose 10% or more of your body weight.

How much more weight do you lose on tirzepatide than semaglutide?

In the head-to-head trial, people on tirzepatide lost about 6.5 percentage points more of their body weight than people on semaglutide. Everyone took a weekly shot at the highest dose they could tolerate, which was 10 or 15 mg of tirzepatide or 1.7 or 2.4 mg of semaglutide (SURMOUNT-5). If you start at 200 pounds, those averages work out to roughly 40 pounds on tirzepatide versus 27 pounds on semaglutide. Waists shrank more on tirzepatide too.

People on tirzepatide were also more likely to lose at least 10%, 15%, 20% and 25% of their weight. Eli Lilly, which makes tirzepatide, paid for the trial, and everyone in it knew which drug they were taking.

The gap also showed up in everyday US prescribing. In six months of records from adults without diabetes, more than twice as many tirzepatide users lost at least 15% of their weight. They did that even though fewer of them reached the higher doses: 42.4% of tirzepatide users got to 10 mg or more, while 67.7% of semaglutide users got to 1.7 mg or more.

Does tirzepatide work for women in perimenopause and after menopause?

Yes. In the main tirzepatide obesity trial, women lost about a quarter of their body weight whether they were before, during or after menopause. A breakdown by reproductive stage found weight loss of 26% before menopause, 23% in perimenopause and 23% after menopause. Women on placebo lost 2% to 3%.

Midlife is when fat tends to increase and shift where it sits, and waists came down too. Women on tirzepatide lost about 8 to 9 inches from their waists (20 to 22 cm), compared with 2 inches or less on placebo (4 to 5 cm).

Almost every woman on tirzepatide, 97% to 98% across the three stages, lost at least 5% of her weight. On placebo, 29% to 33% did.

These numbers compare tirzepatide with placebo, not with semaglutide, so they do not tell you how semaglutide does by menopause stage. Eli Lilly funded this analysis.

Does tirzepatide have more side effects than semaglutide?

For the everyday stomach side effects, no clear difference showed up. A 2026 review that pooled the head-to-head studies found no statistically significant difference in nausea, vomiting, diarrhea, constipation, stomach pain or indigestion. In the 72-week trial, stomach side effects were the most common ones on both drugs. They were mostly mild to moderate and happened mainly while the dose was going up.

Serious side effects were reported nearly twice as often with tirzepatide: 5.7% of people versus 2.9% on semaglutide across three head-to-head studies. More people stopped tirzepatide because of side effects (7.2% versus 5.5%), but that difference was not statistically clear.

The Zepbound (tirzepatide) label carries a boxed warning that tirzepatide causes thyroid C-cell tumors in rats. Neither drug is for you if you or a family member has had medullary thyroid cancer or MEN 2 (multiple endocrine neoplasia type 2). The Wegovy (semaglutide) label also warns about pancreatitis and gallbladder disease, so ask your clinical team what to watch for.

One woman on r/Zepbound never got past the side effects on the starting dose, and stopping was her choice. She wrote, "I started at the lowest dose (2.5 mg), and never increased, due to side effects." She also wrote, "I lost 23 lbs and I got really great at counting calories." Her advice: "Listen to your body while it whispers, before it starts to yell."

If you are planning a pregnancy, the labels differ. The Wegovy Medication Guide says, "You should stop using WEGOVY 2 months before you plan to become pregnant." The Zepbound label says to stop when a pregnancy is recognized, and it does not recommend weight loss during pregnancy.

Is semaglutide cheaper than tirzepatide?

Yes, at brand cash prices. Bought straight from the makers, Wegovy costs $349 a month and Zepbound costs $449 a month once you reach the usual doses. A month here means a 28-day fill.

The year-one totals assume one fill each at Zepbound's 2.5 mg and 5 mg doses and then $449 a month. For Wegovy, they assume two fills at the $199 new-patient price and then pens up to 2.4 mg at $349. On those numbers, brand tirzepatide costs $1,400 more in the first year and $1,300 more in the second.

If you have commercial insurance, check what your own plan would charge before you decide. A covered drug with a savings card can change the math.

Should you start with tirzepatide or semaglutide?

Start with the size of your goal, then weigh side effects, budget and needles.

• If you want to lose 10%, 15% or 20% of your weight or more, tirzepatide gives you better odds. In the pooled head-to-head studies, it made reaching each of those marks more likely, and its lead grew with the size of the goal.
• If your goal is closer to 5%, the pooled studies found no clear difference between the two, and semaglutide costs less at brand cash prices. The six-month US prescribing study did see more tirzepatide users reach 5% (85.7% versus 75.2%), so talk through the size of your goal with your clinical team.
• If needles put you off, semaglutide also comes as a daily Wegovy tablet, with a 25 mg maintenance dose for weight loss. You take it with water only and wait at least 30 minutes before eating, drinking or taking other pills (Wegovy label).
• If you have heart disease or sleep apnea, check the labels. The Wegovy label includes lowering cardiovascular risk in adults. The Zepbound label includes treating moderate to severe obstructive sleep apnea in adults with obesity.
• You take one or the other, not both. The Zepbound label does not recommend combining tirzepatide with any GLP-1 medicine, and semaglutide is one.
• Check that you qualify. Zepbound is for adults with obesity, or adults with overweight who have at least one weight-related health problem. The Wegovy label covers weight loss in adults with obesity.
• Our clinical team can prescribe tirzepatide or semaglutide if it fits your goal, your health history and how your body handles side effects.

Your goal decides which drug makes sense. Bigger goals favor tirzepatide, and a smaller goal, a tighter budget or a dislike of needles can point to semaglutide. Take the quiz so your clinical team can match the medicine to how much you want to lose and how your body handles it.