# GLP-1 medicines by the numbers: the key statistics, honestly sourced

> The headline GLP-1 figures people actually search for — average weight loss by drug, the odds of hitting each milestone, how common the side effects are vs placebo, the rare risks, regain after stopping, and cost — each number tied to its primary source and labeled by evidence type.

**Evidence grade:** Established (rung 1 of 8 on the Peptide Evidence Ladder) · **Last reviewed:** 2026-07-02 · **Source page:** https://thepeptideera.com/evidence/glp1-by-the-numbers

## Short answer
These are trial averages from separate studies — not head-to-head, and not a prediction for any one person. Average weight loss ran about 21% for tirzepatide (Zepbound, SURMOUNT-1), about 16–17% for the oral-semaglutide pill (OASIS), about 15% for semaglutide (Wegovy, STEP 1), and about 11% for the orforglipron pill (Foundayo, ATTAIN-1); the investigational triple-agonist retatrutide reported about 28% at its top dose in a phase-3 readout that isn't yet published. The most common side effects are gastrointestinal (on the Wegovy label, nausea 44% vs 16% on placebo). Serious problems (gallbladder disease, pancreatitis) are uncommon; a rare eye condition (NAION) is an emerging, unproven signal. After stopping, trials show most of the lost weight returns over about a year. This page collects the key numbers, each tied to its source and labeled by how strong that evidence is.

## Key takeaways
- Average weight loss (each drug's own main trial): semaglutide ~15%, tirzepatide ~21%, orforglipron pill ~11%, oral semaglutide ~16–17%; investigational retatrutide ~28% at its top dose (topline, not yet published). Separate trials — not head-to-head, and an average is not a prediction for you.
- Side effects are mostly GI and mostly common-but-mild: on the Wegovy label, nausea 44% vs 16% on placebo, diarrhea 30% vs 16%, vomiting 24% vs 6%, constipation 24% vs 11%.
- Serious problems are uncommon: gallbladder/biliary disease is modestly increased (partly from rapid weight loss); the eye condition NAION is classed 'very rare' (≤1 in 10,000) and is an emerging, unproven signal.
- After stopping, the weight tends to come back: in the STEP 1 extension, participants regained about two-thirds of the lost weight within a year off the drug.

## Safety essentials worth knowing

These apply to GLP-1 and dual/triple-agonist medicines generally. They’re label-level points, not the full list, and not advice about you — your prescriber and the FDA label are the authority.

- **Pregnancy & breastfeeding:** these medicines are not recommended in pregnancy, and intentional weight loss is generally not advised in pregnancy; the labels advise stopping before a planned pregnancy. Breastfeeding status is a conversation to have with your clinician.
- **Birth control:** some of these medicines (such as tirzepatide) can make *oral* contraception less reliable. If you could become pregnant, ask about backup or non-oral contraception.
- **Thyroid boxed warning:** this drug class carries an FDA boxed warning (thyroid C-cell tumours seen in rodents) and is not for people with a personal or family history of medullary thyroid cancer (MTC) or MEN 2.
- **Blood sugar:** combined with insulin or a sulfonylurea, these medicines can cause low blood sugar — those other medicines often need prescriber-managed adjustment, not self-adjustment.
- **Eating disorders:** an appetite-suppressing medicine warrants particular caution with a current or past eating disorder; disclose this to your clinician.
- **Surgery, sedation & endoscopy:** because these medicines slow stomach emptying, tell your surgical or anaesthesia team you take a GLP-1 well in advance — they'll decide with you whether to continue or hold it (more: https://thepeptideera.com/evidence/glp1-and-surgery).

Numbers are where the GLP-1 conversation gets slippery — a "20%!" here, a scary side-effect percentage there, usually with no source and no sense of how strong the evidence is. This page is the opposite: the figures people actually search for, each tied to its primary source and **labeled by evidence type** so you can weigh it. It's education, not a prediction or medical advice. A running rule for the whole page: these are **trial averages and population rates, not forecasts for any one person.**

## How much weight, on average

Each figure is that drug's average in **its own main obesity trial** — separate studies, **not a head-to-head**, and individuals landed all over the average.

| Medicine | Average weight loss | Trial | Evidence |
| --- | --- | --- | --- |
| Tirzepatide (Zepbound) | ~20.9% | SURMOUNT-1, 72 wk (highest dose) | RCT (approved) |
| Oral semaglutide (oral Wegovy) | ~16–17% | OASIS (adherent) | RCT (approved) |
| Semaglutide (Wegovy) | ~14.9% | STEP 1, 68 wk | RCT (approved) |
| Orforglipron pill (Foundayo) | ~11% | ATTAIN-1 | RCT (approved) |
| Retatrutide (triple agonist) | ~28% (top dose) | TRIUMPH-1, phase 3 | **Topline press release, not yet published — investigational** (also ~30% in a higher-BMI subgroup) |

## The odds of hitting each milestone

From the two landmark trials — the share of participants who lost **at least** each amount (treatment-regimen estimand). This is what "individual results vary" looks like in numbers.

| Lost at least… | Semaglutide (STEP 1) | Tirzepatide (SURMOUNT-1) |
| --- | --- | --- |
| 5% | ~86% | ~91% |
| 10% | ~69% | ~84% |
| 15% | ~51% | ~71% |
| 20% | ~32% | ~57% |

## How common are the side effects

From the **Wegovy (semaglutide) label**, reported rates on the drug vs. on placebo. The gap over placebo is roughly the part attributable to the medicine — and a reminder that a chunk of every symptom happens on a sugar pill too.

| Side effect | On the drug | On placebo |
| --- | --- | --- |
| Nausea | 44% | 16% |
| Diarrhea | 30% | 16% |
| Vomiting | 24% | 6% |
| Constipation | 24% | 11% |
| Abdominal pain | 20% | 10% |
| Headache | 14% | 10% |
| Fatigue | 11% | 5% |
| Dyspepsia (indigestion) | 9% | 3% |
| Dizziness | 8% | 4% |
| GERD (reflux) | 5% | 3% |

Most are **mild-to-moderate, dose-related, and ease with time** — see the [side-effects page](/evidence/glp1-side-effects) for the full picture.

## Serious, but uncommon

| Signal | The number | Evidence |
| --- | --- | --- |
| Gallbladder / biliary disease | Modestly increased risk (relative risk ~1.4 in a 76-trial meta-analysis); small absolute risk, partly driven by rapid weight loss | Meta-analysis of RCTs |
| NAION (a rare eye condition) | Classed "very rare" — on the order of **≤1 in 10,000**; cohort data suggest a roughly two-fold association | Emerging / observational — unproven, [details](/evidence/glp1-lesser-known-side-effects) |
| Pancreatitis, bowel obstruction (ileus) | Uncommon but labeled; the reason a few red-flag symptoms warrant prompt care | Labeled; ileus signal largely observational |

## What the numbers say about the benefits beyond weight

| Finding | The number | Evidence |
| --- | --- | --- |
| Cardiovascular risk (semaglutide, SELECT) | ~20% **relative** reduction in major cardiovascular events (a smaller absolute difference — about 1.5 percentage points) in adults with obesity + established CVD | RCT (approved indication) |
| Lean (muscle) mass | In the STEP 1 body-composition sub-study, some of the weight lost was lean mass; the health significance is still being worked out | RCT sub-study — [muscle page](/evidence/glp1-muscle-loss) |

## After you stop

| Finding | The number | Evidence |
| --- | --- | --- |
| Weight regain | In the STEP 1 extension, participants regained about **two-thirds** of the lost weight within a year of stopping | RCT extension |

The takeaway isn't "don't stop" — it's that these medicines treat an ongoing condition, so stopping is a decision to plan with a clinician. See [stopping a GLP-1](/evidence/stopping-glp1) and the [off-ramp planner](/tools/off-ramp).

## Cost & coverage

| Figure | The number | Evidence |
| --- | --- | --- |
| Prior-auth appeals (Medicare Advantage, 2024) | Only **~11.5%** of denied requests were appealed — but **~81%** of those appeals were partially or fully overturned | KFF analysis |

Most denials are never appealed, yet most appeals win — see [cost & access](/evidence/glp1-cost-and-access) for how to appeal.

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Every figure above traces to the sources listed below. Where a number is from a topline press release (retatrutide) or observational data (NAION), it's labeled as such — because a number is only as good as the evidence under it. For how we grade evidence, see [the Evidence Ladder](/evidence/the-evidence-ladder). And what any of these numbers mean *for you* is a conversation with a clinician who knows your history.

## Sources (11)
1. Wilding JPH, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity (STEP 1). N Engl J Med. 2021;384:989–1002. — https://www.nejm.org/doi/full/10.1056/NEJMoa2032183 [RCT]
2. Jastreboff AM, et al. Tirzepatide Once Weekly for the Treatment of Obesity (SURMOUNT-1). N Engl J Med. 2022;387:205–216. — https://www.nejm.org/doi/full/10.1056/NEJMoa2206038 [RCT]
3. Orforglipron, an Oral Small-Molecule GLP-1 Receptor Agonist for Obesity Treatment (ATTAIN-1, phase 3). N Engl J Med. 2025;393:1796–1806. DOI 10.1056/NEJMoa2511774. — https://doi.org/10.1056/NEJMoa2511774 [RCT]
4. Novo Nordisk — FDA approves oral Wegovy (oral semaglutide 25 mg) for weight management (OASIS program; ~16.6% mean loss when adherent). Dec 2025. — https://www.novonordisk.com/content/nncorp/global/en/news-and-media/news-and-ir-materials/news-details.html?id=916472 [NEWS]
5. Eli Lilly — Retatrutide (triple agonist) delivered up to ~30% weight loss in the pivotal phase-3 TRIUMPH-1 trial (topline; not yet peer-reviewed). May 2026. — https://www.prnewswire.com/news-releases/lillys-triple-agonist-retatrutide-delivered-powerful-weight-loss-in-pivotal-phase-3-obesity-trial-302778859.html [NEWS]
6. Wegovy (semaglutide) — FDA Prescribing Information via DailyMed (adverse-reaction rates, Table 3, vs placebo). — https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ee06186f-2aa3-4990-a760-757579d8f77b [LABEL]
7. He L, et al. Association of GLP-1 Receptor Agonist Use With Risk of Gallbladder and Biliary Diseases: Meta-analysis of Randomized Clinical Trials. JAMA Intern Med. 2022. — https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2790392 [META-ANALYSIS]
8. EMA PRAC — NAION is a 'very rare' side effect of semaglutide (up to ~1 in 10,000). June 2025. — https://www.ema.europa.eu/en/news/prac-concludes-eye-condition-naion-very-rare-side-effect-semaglutide-medicines-ozempic-rybelsus-wegovy [OTHER]
9. Lincoff AM, et al. Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes (SELECT; ~20% relative reduction, ~1.5-point absolute, in major cardiovascular events). N Engl J Med. 2023;389:2221–2232. — https://www.nejm.org/doi/full/10.1056/NEJMoa2307563 [RCT]
10. Wilding JPH, et al. Weight regain and cardiometabolic effects after withdrawal of semaglutide: The STEP 1 trial extension. Diabetes Obes Metab. 2022. — https://dom-pubs.onlinelibrary.wiley.com/doi/10.1111/dom.14725 [RCT]
11. KFF — Medicare Advantage prior authorization in 2024 (11.5% of denials appealed; 80.7% overturned). — https://www.kff.org/medicare/medicare-advantage-insurers-made-nearly-53-million-prior-authorization-determinations-in-2024/ [REVIEW]

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From The Peptide Era (https://thepeptideera.com) — evidence-graded, primary-sourced answers about GLP-1 medicines. Education, not medical advice. No doses, no sourcing.