Ranked by how much weight people lost beyond placebo in clinical trials, tirzepatide and retatrutide lead every GLP-1 weight loss drug. Semaglutide, CagriSema, MariTide, mazdutide and amycretin form the next tier. Older diabetes drugs like dulaglutide and exenatide sit near the bottom, and the supplements sold as "natural GLP-1" boosters sit at the very bottom, because none of them contains a GLP-1 drug.
This is an educational overview, not medical advice. Anagen prescribes compounded tirzepatide, which ranks near the top of this list, and compounded semaglutide. Compounded drugs are not FDA-approved and have not been tested in their own clinical trials; every number below comes from trials of the branded or investigational drug.
How were the GLP-1 drugs ranked?
Each drug is ranked by the percentage of body weight lost beyond placebo at its highest tested dose. Subtracting the placebo group removes the weight people lose from diet and exercise counseling alone, which every trial includes. Where a trial reports two methods, we used the one that counts everyone who started the drug, including people who stopped taking it, because that is closer to what happens in real life.
These trials ran for different lengths of time (from 13 to 80 weeks), enrolled different populations and were never run head to head, so the numbers are a guide, not a scoreboard. Side effects, how complete the evidence is and proven health benefits beyond weight were used to break close calls.
Which GLP-1 drug causes the most weight loss?
Retatrutide caused the most weight loss of any GLP-1 drug in a large trial. In TRIUMPH-1, an 80-week Phase 3 trial, people on the 12 mg dose lost 25.0% of their body weight against 3.9% on placebo, a difference of 21.1% (Lilly, May 2026). Counting only people who stayed on the drug, weight loss reached 28.3%. Those are topline results from the company and have not yet been published in a journal.
Tirzepatide is the strongest drug you can be prescribed today. In SURMOUNT-1, people on 15 mg lost 20.9% of their body weight over 72 weeks, against 3.1% on placebo.
| Tier | Drug | Weight lost beyond placebo | Trial | Status |
|---|---|---|---|---|
| S | Retatrutide | 21.1% | Phase 3, 80 weeks | In development |
| S | Tirzepatide (Zepbound, Mounjaro) | 17.8% | Phase 3, 72 weeks | Approved |
| A | Amycretin | about 24% | Phase 1b/2a, 36 weeks | In development |
| A | CagriSema | 17.4% | Phase 3, 68 weeks | Under FDA review |
| A | Mazdutide | 15.5% | Phase 3, 60 weeks | Approved in China |
| A | MariTide | 13.7% | Phase 2, 52 weeks | In development |
| A | Semaglutide (Wegovy, Ozempic) | 12.5% | Phase 3, 68 weeks | Approved |
| B | Survodutide | 13.4% | Phase 3, 76 weeks | In development |
| B | Pemvidutide | 13.4% | Phase 2, 48 weeks | In development |
| B | Ecnoglutide | 13.3% | Phase 3, 40 weeks | In development |
| B | Oral semaglutide 25 mg (Wegovy pill) | 11.4% | Phase 3, 64 weeks | Approved |
| C | Aleniglipron | 11.3% | Phase 2b, 36 weeks | In development |
| C | Orforglipron (Foundayo) | 9.1% | Phase 3, 72 weeks | Approved |
| C | VK2735 | up to 14.7% (total) | Phase 2, 13 weeks | In development |
| C | Danuglipron | not ranked on weight | Phase 2 | Discontinued |
| D | Liraglutide (Saxenda) | 5.4% | Phase 3, 56 weeks | Approved |
| D | Rybelsus (oral semaglutide 14 mg) | about 2 to 4 kg | Phase 3, 26 weeks | Approved for diabetes |
| D | Dulaglutide (Trulicity) | under 2 kg | Meta-analysis | Approved for diabetes |
| D | Exenatide (Byetta, Bydureon) | under 2 kg | Meta-analysis | Approved for diabetes |
Why is semaglutide in A tier if newer drugs beat it?
Semaglutide stays in A tier because it is the only drug on this list proven to reduce heart attacks, strokes and cardiovascular deaths. In the SELECT trial of 17,604 adults with overweight or obesity and heart disease, semaglutide cut those events by 20%. On weight alone, semaglutide's 12.5% beyond placebo in STEP 1 would rank below survodutide and mazdutide.
The other A tier drugs earned their place on weight. CagriSema, a combination of semaglutide and the amylin drug cagrilintide, reached 20.4% against 3.0% on placebo, though it later failed to match tirzepatide in a head-to-head trial. Mazdutide reached 18.6% against 3.0% at 60 weeks in Chinese adults and became the first GLP-1 and glucagon drug approved for weight management, in China in 2025. MariTide, which is injected once a month, reached 16.2% against 2.5% at 52 weeks.
Amycretin posted the largest number on the list, 22.0% at 36 weeks against a 1.9% gain on placebo, but in a trial of only 125 people. It sits in A tier rather than S until a larger trial confirms it.
Which GLP-1 pill works best?
Oral semaglutide 25 mg, sold as the Wegovy pill, produced the most weight loss of any approved GLP-1 pill: 13.6% against 2.2% on placebo at 64 weeks in OASIS 4. It must be taken on an empty stomach with a small sip of water. Orforglipron, approved in 2026 as Foundayo, can be taken at any time without food or water rules, and reached 11.2% against 2.1% on placebo at 72 weeks in ATTAIN-1.
Aleniglipron, a pill still in development, reached 11.3% beyond placebo at 36 weeks in a Phase 2b trial, but 10.4% of people stopped because of side effects. Danuglipron, Pfizer's daily pill, was discontinued in April 2025 after a trial participant developed a liver injury that resolved once the drug was stopped.
Rybelsus is the same molecule as the Wegovy pill at a lower 14 mg dose approved for type 2 diabetes. At that dose it produced about 2 to 4 kg of weight loss beyond placebo over 26 weeks, which is why it ranks in D tier.
Why is VK2735 ranked in C tier?
VK2735 is ranked in C tier because its data is too short to judge. In a Phase 2 trial, the injection produced up to 14.7% weight loss in only 13 weeks, which is fast for any GLP-1 drug. Thirteen weeks says little about where weight loss levels off or how well people tolerate the drug long term, and its Phase 3 results are not expected until the second half of 2027. If those results hold up, VK2735 will move up.
What about side effects?
Every GLP-1 drug causes the same family of side effects, mainly nausea, vomiting, diarrhea and constipation, and they tend to rise with dose and with how much weight a drug takes off. Side effects were used to break close calls rather than to rank on their own.
Retatrutide shows the tradeoff most clearly. At the 12 mg dose in TRIUMPH-1, 11.3% of people stopped because of side effects, against 4.9% on placebo, and 12.5% reported dysesthesia, an unusual skin sensation such as tingling or burning, against 0.9% on placebo. In SURMOUNT-1, 4% to 7% of people on tirzepatide stopped because of side effects. At the other end, only 2% of people on ecnoglutide stopped because of side effects in its Phase 3 trial.
GLP-1 drugs also raise resting heart rate by a few beats per minute, and drugs that also act on the glucagon receptor, such as retatrutide, tend to raise it more. Rapid weight loss on any of these drugs can trigger a temporary shed of hair, which we cover in does Ozempic cause hair loss.
Do natural GLP-1 supplements work?
Supplements marketed as "natural GLP-1" products do not contain a GLP-1 drug. They claim to raise the body's own GLP-1 hormone, which is a different and much weaker effect, and none has shown weight loss close to a prescription GLP-1 drug.
Lemme GLP-1 Daily contains lemon, saffron and red orange extracts; the one study available for review tested a single ingredient in 45 people, not the full formula. Pendulum's GLP-1 Probiotic contains bacterial strains such as Akkermansia; the company's one human trial tested a different formula and found no change in weight. Supergut's GLP-1 Booster is a prebiotic fiber blend. Berberine, often called "nature's Ozempic," produced about 2 kg of weight loss over roughly 12 weeks in a meta-analysis of randomized trials, around 2% of body weight.
Fiber and a balanced diet are worth having on their own merits. They are not a substitute for a GLP-1 drug.
Frequently asked questions
What is the strongest GLP-1 weight loss drug?
Retatrutide produced the most weight loss in a large trial: 25.0% of body weight against 3.9% on placebo over 80 weeks in Lilly's Phase 3 TRIUMPH-1 trial. It is not yet approved. Among approved drugs, tirzepatide is the strongest, with 20.9% against 3.1% on placebo over 72 weeks in SURMOUNT-1.
Is retatrutide better than tirzepatide?
Retatrutide produced more weight loss than tirzepatide in separate trials, about 21% beyond placebo against about 18%, but no head-to-head trial has compared them. Retatrutide also had a higher rate of people stopping because of side effects and is not yet approved, which is why both share the top tier here.
Which GLP-1 pill works best for weight loss?
Among approved pills, oral semaglutide 25 mg (the Wegovy pill) produced the most weight loss, 13.6% against 2.2% on placebo over 64 weeks. Orforglipron (Foundayo) produced somewhat less, 11.2% against 2.1% over 72 weeks, but can be taken at any time of day without food or water restrictions.
Do natural GLP-1 supplements work for weight loss?
Products sold as natural GLP-1 supplements, such as Lemme GLP-1 Daily, Pendulum GLP-1 Probiotic and Supergut GLP-1 Booster, contain no GLP-1 drug. None has shown weight loss close to a prescription GLP-1. Berberine, the most studied, produced about 2 kg of weight loss over roughly 12 weeks in a meta-analysis of trials.
Why is semaglutide ranked below tirzepatide?
Semaglutide produced less weight loss than tirzepatide in their pivotal trials, 12.5% beyond placebo against 17.8%. Semaglutide is still ranked highly because it is the only drug on this list proven to reduce heart attacks, strokes and cardiovascular deaths, by 20% in the SELECT trial.
Is compounded tirzepatide the same as Zepbound?
Compounded tirzepatide contains the same active molecule as Zepbound and Mounjaro, but compounded drugs are not FDA-approved and have not been tested in their own clinical trials. The trial results in this ranking come from the branded drug. A clinician can help you decide which option fits you.
