Which GLP-1 Is Best for Weight Loss? Tirzepatide, Semaglutide and the Two New Pills, by the Trial Numbers
Short answer
Tirzepatide, on the only head-to-head trial that exists. In SURMOUNT-5, 751 adults with obesity were randomised to the highest dose they could tolerate of either tirzepatide (Zepbound) or semaglutide (Wegovy) for 72 weeks. Tirzepatide produced a mean loss of 20.2% of body weight against 13.7% for semaglutide, and more people on tirzepatide reached every threshold from 10% to 25%.1
That settles “strongest”. It does not settle “best for you”. Semaglutide has the cardiovascular-outcomes trial tirzepatide does not yet have, the two pills approved since December 2025 remove the needle at a cost of a few percentage points, and the cash prices in September 2026 are far enough apart to change the answer for many people.
This is not medical advice. Tirzeptides is an independent comparison site, not a healthcare provider. Nothing here creates a doctor-patient relationship or replaces a conversation with a licensed clinician. GLP-1 medications are prescription drugs with real risks and contraindications. Talk to a qualified provider before starting, stopping or changing any treatment.
The numbers, side by side
Every figure below is a trial average under trial conditions. Only the first row is a direct comparison; the rest come from separate trials with different populations and lengths, so treat differences of a point or two as noise.
| Molecule (brand) | How taken | Trial | Average loss | vs placebo |
|---|---|---|---|---|
| Tirzepatide (Zepbound) | Weekly injection | SURMOUNT-5, 72 wk | 20.2% | 13.7% on semaglutide1 |
| Semaglutide (Wegovy) | Weekly injection | STEP 1, 68 wk | 14.9% | 2.4%3 |
| Oral semaglutide 25 mg (Wegovy pill) | Daily tablet, fasting | OASIS 4, 64 wk | 13.6% (16.6% if adherent) | 2.2%5 |
| Orforglipron (Foundayo) | Daily tablet, no food rules | ATTAIN-1, 72 wk | 12.4% highest dose, on treatment (11.1% regardless) | 0.9% (2.1%)4 |
| Liraglutide (Saxenda, now generic) | Daily injection | SCALE, 56 wk | 8.0% | 2.6%6 |
The shape of the ranking is stable across every dataset we have seen: tirzepatide first, injectable semaglutide and the semaglutide pill close together behind it, orforglipron a little further back, liraglutide well behind. Retatrutide, the three-hormone drug reporting 28% in its phase-3 programme, is not approved and Lilly has said it will not file until 2027, so it is not an option you can be prescribed.
“Best” depends on what you are optimising for
- Most weight, fastest: tirzepatide. The 6.5-point gap over semaglutide in SURMOUNT-5 is the largest difference between any two approved options.
- Proven heart protection: semaglutide. SELECT showed a 20% relative reduction in major cardiovascular events in people with established heart disease; tirzepatide's outcomes trial showed it was non-inferior to a diabetes comparator, not a placebo. The detail is in which GLP-1 is best for cardiovascular benefit.
- No needles: the two pills. The Wegovy pill gets closer to injectable results but must be taken on an empty stomach with no more than 4 oz of water, then nothing for 30 minutes.7 Foundayo can be taken at any time with or without food and gives up roughly two to four points for that convenience.4
- Lowest cash price for the brand product: a Wegovy or Foundayo starting dose, both $149 a month self-pay. At maintenance doses the pills are cheaper than the pens.
- Lowest cash price overall: compounded semaglutide through telehealth, which the next section covers.
What each one costs without insurance, September 2026
Manufacturer self-pay prices, checked on the manufacturers' own pharmacy pages on 16 September 2026. All are per month, exclude government-programme beneficiaries, and can be withdrawn at any time.
| Product | Where | Starting dose | Maintenance doses |
|---|---|---|---|
| Zepbound vial or KwikPen | LillyDirect | $299 (2.5 mg) | $399 (5 mg); $449 (7.5–15 mg) if you refill within 45 days, otherwise $499–$6998 |
| Wegovy pen | NovoCare Pharmacy | $199 for the first two fills of 0.25 or 0.5 mg, new patients only, through 31 Dec 2026 | $349 (0.25–2.4 mg); $399 for the 7.2 mg HD pen9 |
| Wegovy pill | NovoCare Pharmacy | $149 (1.5 mg); $199 (4 mg) | $299 (9 and 25 mg)9 |
| Foundayo | LillyDirect | $149 (0.8 and 2.5 mg, the latter reduced through 31 Dec 2026) | $199 (5.5 mg, temporarily reduced); $299 (9–17.2 mg, the top two doses only if you refill within 45 days)10 |
For comparison, the compounded versions sold by US telehealth providers were advertised at $79–$199 a month for semaglutide (median $144) and $129–$299 for tirzepatide (median $179) when we last verified prices on 10 September 2026. Those are sustained plan prices, not first-month teasers, and the full provider-by-provider table with the promo prices separated out is on the GLP-1 price index.
So at maintenance, the cheapest brand-name route to the most effective molecule is about $449 a month, and the cheapest compounded route to the same molecule is about $130–$180. That gap is why the compounded market exists, and the trade-offs that come with it are the subject of the next section.
HealthRX
Best overall · scored 8.2/10
$99/mo semaglutide on a 12-month plan
- LegitScript-certified (certification #50087439)
- Among the lowest per-month pricing on this list
- Same price at every dose level
Which compounded GLP-1 is best?
The molecule question has the same answer: compounded tirzepatide should outperform compounded semaglutide, for the reason SURMOUNT-5 gives. But two caveats apply to compounded products that do not apply to the brands.
First, the trial numbers above were produced with the FDA-approved product at a known potency. A compounded vial is not FDA-reviewed, and if it delivers less drug than the label says, you get less weight loss for reasons that have nothing to do with the molecule. Second, the regulatory ground is moving: the shortages that made compounding legal are over, and the FDA has proposed shutting the bulk-compounding route for both drugs. Is compounded semaglutide still legal? covers where that stands.
So “which compounded GLP-1 is best” is mostly a question about the provider, not the molecule. The things that separate a good one from a bad one:
- A published price before the intake. Two of the eight providers we track make you complete a medical questionnaire before showing a number.
- A named, state-licensed compounding pharmacy and a stated beyond-use date on the vial.
- Month-to-month terms. Prepaying twelve months in a category under active FDA enforcement is the wrong bet.
- No equivalence claims. “Same as Zepbound” is the exact language the FDA's warning letters have targeted.
We score providers on those criteria, in the open, and the ranking is never adjusted by what a provider pays us. The current ranking is here and how the score is built is here.
Who should not chase the biggest number
More drug means more side effects, and the gastrointestinal ones scale with dose and molecule. If you have already struggled with nausea on semaglutide, tirzepatide is not an automatic upgrade. All of these drugs carry the same boxed warning about thyroid C-cell tumours and are not for anyone with a personal or family history of medullary thyroid carcinoma or MEN 2, and none should be used in pregnancy. Oral contraceptives are less reliable around dose increases on both tirzepatide and orforglipron. The side-effects guide covers the full list, and how long GLP-1 side effects last has the trial data on how quickly they ease.
Losing weight also does not stop at the maintenance dose; it plateaus in the second year, and stopping reverses much of it. How fast does GLP-1 weight loss happen? has the month-by-month picture.
The short version
Tirzepatide is the most effective GLP-1 for weight loss, by about 6.5 points over semaglutide in the one trial that compared them directly. Semaglutide is the one with proven heart protection. The Wegovy pill is the most effective needle-free option; Foundayo is the most convenient. Cash prices in September 2026 run from $149 for a starting-dose pill to $449 for maintenance-dose Zepbound, with compounded versions at roughly a third of that. If you want the molecule comparison in more depth, read tirzepatide vs semaglutide; if you want to know what you would actually pay, the price index is updated whenever we re-verify.
Sources
- Tirzepatide as Compared with Semaglutide for the Treatment of Obesity (SURMOUNT-5) — New England Journal of Medicine, 2025
- SURMOUNT-5: Greater Loss of Weight, Waist Circumference With Tirzepatide Than Semaglutide — American College of Cardiology
- Once-Weekly Semaglutide in Adults with Overweight or Obesity (STEP 1) — New England Journal of Medicine, 2021
- FDA approves Lilly's Foundayo (orforglipron), the only GLP-1 pill for weight loss that can be taken any time of day without food or water restrictions — Eli Lilly and Company, 1 April 2026
- Oral Semaglutide at a Dose of 25 mg in Adults with Overweight or Obesity (OASIS 4) — New England Journal of Medicine, 2025
- A Randomized, Controlled Trial of 3.0 mg of Liraglutide in Weight Management (SCALE) — New England Journal of Medicine, 2015
- Wegovy Pill Guide and Dosing Information — Novo Nordisk
- Zepbound self-pay pricing — LillyDirect, accessed 16 September 2026
- Wegovy Cost and Coverage Information — Novo Nordisk, accessed 16 September 2026
- Foundayo self-pay pricing — LillyDirect, accessed 16 September 2026
Our top three, compared
Ranked by the six published weights on how we rank. All three are paid partners.
Related questions
- Which GLP-1 is best for cardiovascular benefit?
- What does GLP-1 do in the body?
- How long do GLP-1 side effects last?
- How fast does GLP-1 weight loss happen?
- Does compounded GLP-1 need to be refrigerated?
All GLP-1 questions answered → · GLP-1 price index → · Compare the 8 providers →