Best Injection for Weight Loss? Every Approved Shot, Ranked on Trial Data

Zepbound (tirzepatide) has produced the most weight loss of any injection FDA has approved for weight: the 15 mg dose averaged 20.9% over 72 weeks where placebo averaged 3.1%, and it won 20.2% to 13.7% when randomized against semaglutide.^[1][4] Wegovy (semaglutide) comes second on weight and first on proof of protection from heart attacks and strokes, the one reason a person with established heart disease might choose it over the stronger drug.^[2][5] Which shot is best therefore depends on what you need it to do.

Which weight loss injection works best?

Three brands hold a US license for weight in the general adult population: Zepbound, Wegovy and Saxenda.^[1][2][3] Wegovy comes in two maintenance strengths, 2.4 mg and the higher 7.2 mg sold as Wegovy HD. The table lists each at the result printed in its label, for adults without diabetes.

Only one rung of that ladder comes from a direct comparison. SURMOUNT-5 randomized 751 adults with obesity to tirzepatide or semaglutide at the highest dose each person could tolerate, and it favored tirzepatide by 6.5 points at 72 weeks.^[4] The trial was open label and funded by Lilly, and its top semaglutide dose was 2.4 mg, so it says nothing direct about Wegovy HD. No randomized trial has compared 7.2 mg with tirzepatide. The gap between them in the table crosses separate trials with different participants, and the head-to-head trial and what it settles explains why that matters.

The higher Wegovy dose added 3.1 points over 2.4 mg in its own randomized comparison.^[7] Within Zepbound, going from 10 mg up to 15 mg added little on average,^[1] and the 5 mg dose fell well short of both.

Expect a smaller number with type 2 diabetes, since every drug here did less in those trials: 14.7% on Zepbound 15 mg, 13.2% on Wegovy HD, 9.6% on Wegovy 2.4 mg and 5.4% on Saxenda.^[1][2][3]

What does the largest analysis of the trials say?

A 2026 BMJ network meta-analysis pooled 262 trials and 99,791 people. Measured against lifestyle changes alone at one year, tirzepatide took off 14.9% more body weight and subcutaneous semaglutide 9.8% more.^[5] Those figures are smaller than the label results because they are differences from a comparison group, measured at one year and pooled across doses and populations, including people with diabetes. The order is the same. A 2025 analysis in Nature Medicine of 56 trials also found more than 10% for semaglutide and tirzepatide, ahead of the older drugs.^[6] What 262 trials say together has the BMJ’s other findings.

Which injection has the fewest side effects?

None of them is easy on the gut, and the labels are hard to rank because the trials differ. These are the rates printed in each label, each beside its own placebo group.

Three further differences stand out. Wegovy HD carries a side effect few people expect: dysesthesia, abnormal skin sensation, in 22% against 6% on 2.4 mg and 0.3% on placebo, which is weighed in what the 7.2 mg dose costs you.^[2] Liraglutide is among the drugs the BMJ analysis ranked highest for stopping because of side effects, which the Saxenda figure reflects.^[5][3] And tirzepatide removed the most fat, by 25.7%, and also the most lean mass, by 8.3%.^[5]

All of these labels share serious warnings, including thyroid C-cell tumors in rodents, and none may be used by people whose own or close family's medical history includes medullary thyroid cancer or MEN 2.^[1][2][3] That warning applies across the group, so it does not separate one shot from another.

Which injection protects your heart?

On this question the order changes. In SELECT, 17,604 people who had overweight or obesity and existing cardiovascular disease took semaglutide 2.4 mg or placebo, and major cardiovascular events fell by 20% (hazard ratio 0.80).^[8][2] Wegovy is licensed for that purpose. In the BMJ analysis, subcutaneous semaglutide was the only obesity drug linked to fewer deaths (risk ratio 0.81) and fewer heart attacks (0.72), mostly because of trials in high-risk people.^[5]

Tirzepatide has not had the same test in people without diabetes. Among people with type 2 diabetes and cardiovascular disease, SURPASS-CVOT found it noninferior to dulaglutide (hazard ratio 0.92), short of superiority.^[9] Its obesity outcomes trial, SURMOUNT-MMO, has not finished; its primary completion is estimated for October 2027.^[10] So this is a gap in the evidence, with no finding of harm. Both drugs reduced heart failure risk in the BMJ analysis (0.43 for semaglutide, 0.49 for tirzepatide), and no drug improved quality of life beyond the size the authors considered meaningful.^[5]

Other licensed uses also differ. As of November 2026, Zepbound also carries a sleep apnea indication for adults with obesity, and Wegovy injection one for MASH, a fatty liver disease, at fibrosis stages F2 to F3 without cirrhosis.^[1][2]

How should you match the injection to your goal?

• Most weight off: tirzepatide, on both label and head-to-head evidence.^[1][4]
• Established heart disease: semaglutide has the licensed indication and outcome trial; tirzepatide’s obesity trial has not reported.^[2][10]
• Sleep apnea with obesity: Zepbound has the indication.^[1]
• MASH with F2 to F3 fibrosis: Wegovy has the indication.^[2]
• Trouble with side effects on one drug: the two may behave differently in you, but label rates cannot predict that for an individual. Our Wegovy and Zepbound comparison sets them side by side.

Whichever you take, stopping usually brings weight back. In the withdrawal trials, people switched to placebo regained 14.0% from week 36 to week 88 after Zepbound and 6.9% from week 20 to week 68 after Wegovy, while those who stayed on the drug kept losing.^[1][2] Staying on it matters, so cost and access count as well as trial results. Those are questions for the weight-loss shot names and prices board.

What about the shots not on this list?

Ozempic and Mounjaro. Ozempic shares its molecule with Wegovy and Mounjaro with Zepbound, but both are labeled for type 2 diabetes, so using them for weight alone is off-label.^[18][19]

Imcivree. This injection is approved only for specific rare forms of obesity, such as Bardet-Biedl syndrome and confirmed genetic deficiencies, plus acquired hypothalamic obesity, so it does not compete for general use.^[17]

Saxenda. FDA’s shortage database lists it as limited in availability until discontinuation in January 2027.^[16] Its label says to stop after 16 weeks when weight is down by less than 4%.^[3]

CagriSema and retatrutide. Neither was approved as of November 2026. CagriSema produced 20.4% against 3.0% on placebo over 68 weeks, and Novo filed it with FDA in December 2025.^[11][12] When it was tested against tirzepatide 15 mg, Novo reported that it missed its primary endpoint, with 20.2% against 23.6% at 84 weeks in an open-label trial, so it would not displace tirzepatide on current evidence.^[20] Retatrutide produced 25.0% at 12 mg against 3.9% on placebo over 80 weeks, the largest figure in any phase 3 obesity trial listed here, though it has not been randomized against tirzepatide in that trial.^[13] Lilly plans to submit it in the first quarter of 2027 and says it cannot be legally sold or marketed for human use.^[14] See what the retatrutide evidence shows.

Compounded semaglutide and tirzepatide. FDA does not review a compounded drug's safety, effectiveness or quality before it is sold, so the trial results above belong to the approved products.^[15]