Weight loss and side effects: Wegovy, Zepbound, and Foundayo compared
If you're weighing the three medications covered under the Medicare GLP-1 Bridge, the natural questions are "how much weight will I lose?" and "how will I feel on it?" Here's a plain-English summary of what the published clinical trials actually showed — so you can have a more informed conversation with your doctor.
How much weight loss? (trial averages)
| Medication | Trial | Avg. body-weight reduction | Form |
|---|---|---|---|
| Foundayo (orforglipron 36 mg) | ATTAIN-1, 72 weeks | about 11% (−11.2%) | Once-daily oral pill |
| Wegovy injection (semaglutide 2.4 mg) | STEP-1, 68 weeks | about 15% (−14.9%) | Weekly injection |
| Wegovy HD injection (semaglutide 7.2 mg) | STEP UP, 72 weeks | about 21% (−20.7%) | Weekly injection (higher dose, new 2026) |
| Wegovy oral (semaglutide 25 mg pill) | OASIS-4, 64 weeks | about 17% (−16.6%, full adherence) | Once-daily pill |
| Zepbound (tirzepatide 15 mg) | SURMOUNT-1, 72 weeks | about 21% (−20.9%) | Weekly injection (KwikPen) |
New for 2026: a higher-dose Wegovy HD (semaglutide 7.2 mg injection) was approved in March 2026 and reaches about 20.7% average weight loss — close to tirzepatide's level, and the highest yet for a Wegovy injection. Because the Bridge covers all Wegovy dose strengths, it's included. Side effects look much like the standard dose: gastrointestinal effects were modestly more common at 7.2 mg than 2.4 mg (about 71% vs 61% of patients), though stopping because of them stayed low (3.3% vs 2.0%). One more distinctive finding worth raising with a clinician: altered skin sensation (dysesthesia) was reported more often at the 7.2 mg dose than at 2.4 mg.
Placebo groups in each trial lost only about 2–3% on average. And dose matters: with tirzepatide and orforglipron, higher maintenance doses produced more weight loss — so the headline numbers above are the top doses, not what a starting dose delivers.
Weight loss and tolerability by dose
Worth understanding before you start: the lower doses are usually titration steps to ease side effects, and the studied weight loss comes from reaching and staying on a maintenance dose. Tirzepatide and orforglipron have several maintenance-dose options with a clear trade-off — more weight loss at higher doses, but also more people stopping because of side effects. The two semaglutide products have essentially one target dose each.
| Medication (trial) | Dose | Avg. weight loss | Stopped due to side effects |
|---|---|---|---|
| Foundayo (orforglipron) ATTAIN-1 | 6 mg 12 mg 36 mg | −7.5% −8.4% −11.2% | 5.3% 7.9% 10.3% |
| Wegovy injection (semaglutide) STEP-1 | 2.4 mg (target) | −14.9% | ~7% |
| Wegovy oral (semaglutide) OASIS-4 | 25 mg (target) | −16.6% | 6.9% |
| Zepbound (tirzepatide) SURMOUNT-1 | 5 mg 10 mg 15 mg | −15.0% −19.5% −20.9% | 4.3% 7.1% 6.2% |
The reassuring takeaway: even at the highest doses, roughly 90% or more stayed on treatment through the trials. But tolerability is individual, and dose escalation is exactly where side effects tend to peak. A lower dose generally isn't a way to get the same weight loss with fewer side effects — it usually means less of both. Your clinician titrates toward the dose that balances results and tolerability for you.
A closer look at oral Wegovy by dose
Oral Wegovy isn't started at full strength — it's titrated up over about three months to ease gastrointestinal side effects, then held at the 25 mg maintenance dose:
| Dose | Typical timing | Role | Avg. weight loss |
|---|---|---|---|
| 1.5 mg | Weeks 1–4 | Starting / titration step | — |
| 4 mg | Weeks 5–8 | Titration step | — |
| 9 mg | Weeks 9–12 | Titration step | — |
| 25 mg | Week 13 onward | Maintenance dose | about 16.6% (≈14% intention-to-treat) |
The takeaway: the 1.5, 4, and 9 mg steps are about getting onto the medication comfortably — they ease the GI side effects as the dose climbs. How much weight loss they produce on their own is uncertain: a patient may well lose weight on a lower step, but the amount isn't established, because the trials measured weight loss at the 25 mg maintenance dose. So stopping at a lower step shouldn't be assumed to deliver the full trial results. Your clinician guides the titration based on how you tolerate each step.
What if you can't reach the top dose?
Plenty of people don't tolerate the maximum dose — and that's okay; many do well on a lower one. The honest part is setting expectations, and it differs by medication:
- Wegovy (semaglutide — injection or pill): the strong weight-loss data sits at the established maintenance doses — the 2.4 mg weekly injection (and now the higher 7.2 mg Wegovy HD), or the 25 mg daily pill. At the lower titration doses below those, weight loss is uncertain: indirect evidence from diabetes and dose-finding studies suggests people do still lose weight, but how much at any given lower dose isn't well established, and it varies a lot from person to person.
- Zepbound (tirzepatide): here the news is better. Its lower maintenance doses are themselves well-studied and effective — about 15% at 5 mg and 19.5% at 10 mg in SURMOUNT-1. So someone who settles at 5 or 10 mg for tolerability still has strong, documented weight loss to expect — not the full 15 mg result, but close to it.
The practical point for both: your clinician titrates to the dose that balances results and tolerability for you, which may not be the maximum — and for tirzepatide especially, a well-tolerated middle dose is a perfectly good place to land.
The one head-to-head trial: SURMOUNT-5
Because cross-trial numbers aren't a fair comparison, the most reliable read comes from SURMOUNT-5, which randomly assigned people with obesity to tirzepatide or injectable semaglutide (the 2.4 mg weekly dose) and followed them for 72 weeks. Tirzepatide produced greater average weight loss: −20.2% versus −13.7% of body weight. About 32% of the tirzepatide group lost at least a quarter of their body weight, versus about 16% on semaglutide. (Orforglipron was not in this trial.)
How you take each one
These differ a lot in day-to-day use — which can matter as much as the numbers. Always follow your pharmacist's directions and the official manufacturer instructions; the links below go to the makers' patient guides (with videos and PDFs).
- Foundayo (orforglipron pill): one tablet once a day, any time, with or without food and no water restriction — swallowed whole. That flexibility is its main day-to-day advantage over the Wegovy pill. Foundayo prescribing information (FDA, PDF).
- Wegovy / Wegovy HD injection (semaglutide): a once-weekly shot under the skin — abdomen, thigh, or upper arm — on the same day each week, any time, with or without food, from a single-dose auto-injector pen. The needle is built in and hidden, so there's nothing separate to attach or buy. How to take Wegovy (Novo Nordisk).
- Wegovy oral (semaglutide pill): one tablet each morning on an empty stomach, with no more than 4 oz of plain water, then wait at least 30 minutes before eating, drinking, or taking other medicines — and swallow it whole. Wegovy pill guide (Novo Nordisk).
- Zepbound KwikPen (tirzepatide): a once-weekly shot under the skin — abdomen, thigh, or upper arm — from a multi-dose pen holding four weekly doses; prime it before each use with a new pen needle. Unlike the Wegovy pens, the KwikPen doesn't come with needles — you'll need compatible pen needles (commonly 4 mm or 5 mm), which your doctor can prescribe or you can buy over the counter at a pharmacy. How to use Zepbound (Lilly) · KwikPen instructions (PDF).
These links go to third-party manufacturer and FDA pages; we're independent and not affiliated with them. Always follow your own clinician's and pharmacist's instructions.
Common side effects
For all three, the most common side effects are gastrointestinal: nausea, diarrhea, vomiting, and constipation. They're usually mild to moderate, tend to appear when the dose is being increased, and often ease over time. Most people in the trials stayed on treatment, but a minority stopped because of side effects. In the head-to-head SURMOUNT-5 trial, gastrointestinal side effects led to stopping the medication in 2.7% of tirzepatide users versus 5.6% of semaglutide users — a reminder that tolerability is individual and worth tracking with your doctor.
The two semaglutide forms are worth separating here too. In its trial, the injectable (STEP-1) reported nausea in about 44% of people and vomiting in about 25%; the oral pill (OASIS-4) reported nausea in about 47% and vomiting in about 31%. Tirzepatide's trial reported somewhat lower rates. These come from different studies, so they aren't a true head-to-head comparison — but the pattern holds: GI effects are common with all of them, usually mild to moderate, and most pronounced while the dose is being increased.
Safety notes worth raising with your clinician
These are educational highlights, not a complete list — your clinician reviews your full history.
- These medications carry a boxed warning for thyroid C-cell tumors (based on rodent studies) and are not for people with a personal or family history of medullary thyroid carcinoma or MEN2.
- Use caution with a history of pancreatitis, gallbladder disease, or severe gastrointestinal conditions.
- They are not FDA-approved to treat type 1 diabetes — though some specialists do use them off-label alongside insulin, that's an individualized decision — and are generally stopped in pregnancy or when planning pregnancy.
- Tell your clinician about all your conditions and medications so they can weigh benefits and risks for you specifically.
What happens if you stop? (weight regain)
This is the part that surprises people most: these medications work on the biology of appetite, so when you stop, that effect fades, appetite returns, and weight tends to come back. The trials are consistent on this:
- Semaglutide (STEP-1 extension): a year after stopping, people had regained about two-thirds of the weight they'd lost.
- Tirzepatide (SURMOUNT-4): people who switched to placebo regained about 14% of body weight, while those who stayed on it kept the loss off.
- Semaglutide (STEP-4): at the point of stopping, those who continued held — and even extended — their loss, while those who switched to placebo steadily regained.
The honest takeaway: for most people, keeping the weight off requires staying on some form of GLP-1 therapy — it's treatment for a chronic condition, not a short course you finish. Losing the weight and then maintaining it by willpower alone, after stopping, isn't what the data shows. (Real-world regain may be somewhat slower than in the trials, but it still happens.) Because the Bridge itself runs only through December 31, 2027, this is worth planning for early — see what happens after the Bridge ends. Your clinician can help you map out a long-term plan.
So which one?
That's a decision for you and your clinician, and the "best" choice depends on more than the average number. On the evidence: at their top doses, tirzepatide (Zepbound) and the new Wegovy HD injection (semaglutide 7.2 mg) produce the most weight loss — roughly 21% and 20.7%. The one head-to-head trial favored tirzepatide, but it compared it with the standard 2.4 mg Wegovy, not the new HD dose. Standard Wegovy (injection or pill) is also highly effective, and its injection has the longest track record of these for weight management — though the pill has a far shorter one. Orforglipron (Foundayo) offers a once-daily pill with somewhat lower average weight loss — a meaningful option if avoiding injections matters to you. Tolerability, your other health conditions, pill-versus-injection preference, and cost all factor in. All of them are covered under the Bridge for the same $50 monthly copay for people who qualify.
Frequently asked questions
Which GLP-1 causes the most weight loss?
In the one head-to-head trial (SURMOUNT-5), tirzepatide (Zepbound) produced greater average weight loss than semaglutide (Wegovy) — about 20.2% versus 13.7% at 72 weeks. That trial used the standard 2.4 mg Wegovy dose, though — not the newer Wegovy HD (7.2 mg), which reached about 20.7% in its own trial, close to tirzepatide's level. The two higher doses haven't been compared head-to-head. These are averages; individual results vary.
Is the Foundayo pill as effective as the injections?
In its trial, orforglipron (Foundayo) averaged about 11% body-weight reduction at the top dose — meaningful, but on average less than the injectables. It's an oral pill, which some people prefer. Note that the Wegovy oral pill (semaglutide 25 mg) is a different medication and showed higher average loss than Foundayo.
Is the Wegovy pill as effective as the Wegovy injection?
In its own trial (OASIS-4), the oral semaglutide 25 mg pill produced about 16.6% average weight loss with full adherence — broadly comparable to the injectable Wegovy from STEP-1. The pill is taken daily; the injection weekly. Your clinician helps choose.
Are the side effects different between them?
All are mostly gastrointestinal and usually mild to moderate. In the head-to-head trial, GI side effects led to stopping in 2.7% of tirzepatide users versus 5.6% of semaglutide users.
Are these results guaranteed?
No. They're trial averages with specific doses and durations; real-world results vary and weight returns if the medication stops. Your clinician decides what's appropriate.
Can I take a lower dose of Wegovy or Zepbound?
Often, yes — not everyone tolerates the top dose, and your clinician can settle you on a lower one. The trade-off differs by drug: tirzepatide's lower maintenance doses (5 mg, 10 mg) are well-studied, averaging about 15% and 19.5% weight loss, so a middle dose still works well. For Wegovy, the strongest data is at the top dose (injection 2.4 mg, pill 25 mg); lower doses still help but with less data and more variability.
Does the Medicare GLP-1 Bridge require reaching the highest dose to stay covered?
Based on the published program materials, the Bridge's prior authorization is based on the eligibility criteria (the BMI tiers), not on reaching a specific dose — and after the first approved fill, refills continue through 2027 without a new authorization unless you switch medications. So the published rules don't appear to require stepping up to a maximum dose. Confirm specifics against current CMS materials, since operational details can vary.
Will I regain the weight if I stop the medication?
Usually, at least partly — yes. In trials, people regained about two-thirds of their lost weight a year after stopping semaglutide, and about 14% of body weight after stopping tirzepatide. Keeping the weight off generally requires staying on some form of GLP-1 therapy; it's treatment for a chronic condition, not a short course.
What is Wegovy HD, and is it covered by the Bridge?
Wegovy HD is a higher-dose Wegovy injection — semaglutide 7.2 mg — approved in March 2026, averaging about 20.7% weight loss (close to tirzepatide). Because the Bridge covers all dose strengths of the Wegovy pen, it's included for the same $50 copay for people who qualify.
Sources and review status: Content reviewed June 27, 2026. Efficacy and safety figures are from the published pivotal trials: STEP-1 (semaglutide, N Engl J Med 2021), SURMOUNT-1 (tirzepatide, N Engl J Med 2022), SURMOUNT-5 head-to-head (tirzepatide vs semaglutide, N Engl J Med 2025), and ATTAIN-1 (orforglipron, N Engl J Med 2025). Coverage details from CMS Medicare GLP-1 Bridge. Always confirm current prescribing information and discuss your situation with your clinician.