GLP-1 drugs: a practical guide
Starting and stepping up, side effects and what helps, protein and muscle, stopping, and what compounded and research versions are, for semaglutide, tirzepatide and the rest of the class.
Which drug is which
| Drug | Acts on | Taken | Approval |
|---|---|---|---|
| Semaglutide | GLP-1 | Once weekly, subcutaneous injection | Approved in the US |
| Liraglutide | GLP-1 | Once daily, subcutaneous injection | Approved in the US |
| Exenatide | GLP-1 | Twice daily, subcutaneous injection | Approved in the US |
| Orforglipron | GLP-1 (a pill, not a peptide) | Once daily, by mouth (tablet) | Approved in the US |
| Tirzepatide | GIP and GLP-1 | Once weekly, subcutaneous injection | Approved in the US |
| Survodutide | Glucagon and GLP-1 | Once weekly, subcutaneous injection | Investigational |
| Mazdutide | Glucagon and GLP-1 | Once weekly, subcutaneous injection | Approved outside the US |
| Retatrutide | GIP, GLP-1 and glucagon | Once weekly, subcutaneous injection | Investigational |
| Cagrilintide | Amylin (used with semaglutide) | Once weekly, subcutaneous injection | Investigational |
In separate placebo-controlled trials, counting everyone randomized, average weight loss was 11.2% with orforglipron’s top dose at 72 weeks, 14.9% with semaglutide 2.4 mg at 68 weeks, 18.7% with semaglutide 7.2 mg at 72 weeks, 20.4% with CagriSema at 68 weeks, 20.9% with tirzepatide 15 mg at 72 weeks and 25.0% with retatrutide 12 mg at 80 weeks, vs 2.1 to 3.9% on placebo. The trials enrolled different people, so this isn’t a ranking. How they work and their shared warnings are on the GLP-1 class page.
Starting and stepping up
Labels start low and raise the dose in steps, because stomach side effects come mostly after each increase.
| Drug (label) | Steps | How often |
|---|---|---|
| SemaglutideWegovy | 0.25 → 0.5 → 1 → 1.7 → 2.4 mg | every 4 weeks |
| TirzepatideZepbound | 2.5 → 5 → 7.5 → 10 → 12.5 → 15 mg | every 4 weeks |
| LiraglutideSaxenda | 0.6 → 1.2 → 1.8 → 2.4 → 3 mg | every week |
| OrforglipronFoundayo | 0.8 → 2.5 → 5.5 → 9 → 14.5 → 17.2 mg | every 30 days or more |
Wegovy’s maintenance dose is 2.4 mg, or 1.7 mg; adults who have tolerated 2.4 mg for at least 4 weeks and need more weight loss may go up to 7.2 mg (Wegovy HD, approved in March 2026). Zepbound’s maintenance dose is 5, 10 or 15 mg, and Foundayo’s steps above 5.5 mg are taken only if needed. After 2 or more missed weekly doses, Wegovy’s label restarts at a lower dose; missed doses has each label’s rule.
Side effects and what helps
Stomach side effects are the most common: across the main trials, nausea affected 25 to 44% of people, diarrhea 19 to 30%, constipation 17 to 24%, vomiting 8 to 24% and stomach pain 9 to 20%. They come mostly in the first weeks and after each dose increase, and tend to ease on a steady dose. Fewer than 10% of trial participants stopped because of them.
- Eat smaller, more frequent meals, and avoid fatty or very high-fiber foods in the first few days of treatment.
- Nausea is often worst in the morning or after long gaps without food. Skipping meals because of nausea can make it worse.
- Drink enough to stay hydrated. Losing fluid through vomiting or diarrhea can harm the kidneys.
- Constipation is common; fluids and fiber from food help, though some people need more.
Severe stomach pain that won’t go away, upper-stomach pain with fever or yellow skin, and other warning signs are in Is something wrong? Every compound’s answers: nausea and diarrhea or constipation.
Protein, muscle and bone
Weight lost on these drugs includes muscle and other lean tissue. In a body-scan substudy of 160 people in tirzepatide’s SURMOUNT-1 trial, weight fell 21.3%, fat 33.9% and lean mass 10.9% over 72 weeks: about a quarter of the weight lost was lean mass, the same share as with the smaller loss on placebo.
A 2025 advisory from four medical and nutrition societies recommends pairing the drugs with strength training at least 3 times a week and at least 150 minutes of moderate aerobic activity, to protect muscle and bone. For protein, the usual daily allowance is 0.8 g per kg of body weight; targets of 1.2 to 1.6 g per kg have been proposed during weight loss, though it’s unclear which body weight to use.
Eating much less can leave gaps in iron, calcium, magnesium, zinc and vitamins A, D, E, K, B1, B12 and C, especially below about 1,200 calories a day for women or 1,800 for men. Fatigue beyond what’s expected, heavy hair shedding, flaky or itchy skin, weakness, slow-healing wounds and easy bruising can be signs. The advisory says supplements such as vitamin D, calcium, B12 or a multivitamin can be considered for nutrients at risk. Fast weight loss is also linked with bone loss, more so in older people and women.
Hair and face
Hair loss. In Zepbound’s weight trials, hair loss was reported by 7.1% of women and 0.5% of men on the drug, vs 1.3% and none on placebo, and its label ties it to weight loss; no one on tirzepatide stopped because of it. Hair loss has every compound’s answer.
“Ozempic face.” A popular term, not a diagnosis, for facial volume loss that makes the face look older after weight loss on a GLP-1 drug. A 2025 systematic review found 23 plastic surgery papers describing it, of limited quality.
Stopping
For weight, the labels describe long-term use. Trials that stopped the drug saw most of the weight return:
| Trial | On the drug first | After switching to placebo |
|---|---|---|
| Semaglutide, STEP 1 extension | 17.3% lost over 68 weeks | Two-thirds of it regained within a year off treatment; most heart and blood sugar gains faded too |
| Semaglutide, STEP 4 | 10.6% lost over 20 weeks | Weight rose 6.9% over 48 weeks, vs a further 7.9% loss for those who stayed on it |
| Tirzepatide, SURMOUNT-4 | 20.9% lost over 36 weeks | Weight rose 14.0% over 52 weeks, vs a further 5.5% loss for those who stayed on it |
Compounded and research versions
Compounded semaglutide and tirzepatide. Pharmacies could copy them while they were in shortage. FDA declared the tirzepatide shortage over in October 2024, confirming it that December, and the semaglutide shortage over in February 2025; the grace periods ended in spring 2025, after courts declined to block them. Now a pharmacy may compound a copy only for an individual patient whose prescriber documents a significant difference the patient needs, and FDA says it won’t act against one filling four or fewer such prescriptions a month. Outsourcing facilities can’t make them from bulk ingredients at all. Compounded drugs aren’t FDA-approved, and FDA doesn’t review them for safety, effectiveness or quality.
Salt forms. Semaglutide sodium and semaglutide acetate are different ingredients from the semaglutide in the approved drugs, and FDA says it knows of no lawful basis for compounding with them.
Added vitamins. Some compounded semaglutide comes mixed with vitamin B12. FDA says an added ingredient doesn’t by itself make a compounded drug different from the approved one: it may treat a semaglutide and B12 injection as a copy when each amount is within 10% of an approved product’s strength.
Vials and dosing errors. Compounded vials are measured in a syringe, and mixing up units, mL and mg has led people to inject 5 to 20 times the intended dose, FDA reports. The calculator shows both units and mL. FDA advises throwing a multiple-dose vial away 28 days after first use, even if medicine is left or the compounder’s instructions allow longer, and using a new sterile needle and syringe for every dose. A vial that arrived warm or looks wrong: Is something wrong?
Reported harms. As of May 31, 2026, FDA had received 990 reports of adverse events with compounded semaglutide and more than 730 with compounded tirzepatide. Reports alone don’t show the drug caused each problem.
“Research” GLP-1s. FDA has warned sellers of semaglutide, tirzepatide and retatrutide labeled “for research purposes,” and retatrutide can’t be compounded at all. Some sell tirzepatide as “GLP-2” and retatrutide as “GLP-3”; see names that mislead, and testing and fakes for what tested vials held.
Patches and supplements. Every approved GLP-1 drug is an injection or a tablet. No patch, drop or supplement has been approved to deliver one.
Pills or shots
Semaglutide comes as daily tablets, Rybelsus for type 2 diabetes and Wegovy tablets for weight, taken on an empty stomach with no more than 4 ounces of water, then a wait of at least 30 minutes before eating, drinking or taking other pills. Only about 0.4 to 2% of each tablet reaches the blood, so tablet doses are far higher than injected ones.
Orforglipron (Foundayo), approved in April 2026 for weight, is a daily tablet that isn’t a peptide, and its label allows it at any time, with or without food. In its main trial the top dose lowered weight 11.2% at 72 weeks; the weekly semaglutide injection lowered it 14.9% at 68 weeks in a separate trial. Orforglipron vs semaglutide compares them.
What’s coming
Where the next weight-loss drugs stood in early October 2026, roughly from furthest along to newest in phase 3. Weight loss is from each drug’s main trial so far, published or announced; the trials enrolled different people for different lengths of time, so this isn’t a ranking.
- CagriSemaAmylin and GLP-1: cagrilintide with semaglutide
- Filed with FDAFiled with FDA in December 2025; a decision is expected in the fourth quarter of 2026. Weekly injection. Weight loss so far: 20.4% at 68 weeks vs 3.0% on placebo (REDEFINE 1); 20.2% vs 23.6% on tirzepatide 15 mg at 84 weeks (REDEFINE 4), short of its goal of matching tirzepatide.
- RetatrutideGIP, GLP-1 and glucagon
- Phase 3Phase 3 trials reported in 2026; its maker plans to file in early 2027. Weekly injection. Weight loss so far: 25.0% on 12 mg at 80 weeks vs 3.9% on placebo (TRIUMPH-1).
- SurvodutideGlucagon and GLP-1
- Phase 3Phase 3 obesity trials reported in 2026; liver trials continue; no filing announced. Weekly injection. Weight loss so far: 12.2 to 13.0% at 76 weeks vs 5.4% on placebo (SYNCHRONIZE-1).
- MazdutideGlucagon and GLP-1
- Approved in ChinaApproved in China since June 2025, and nowhere else. Weekly injection. Weight loss so far: 11.0 to 14.0% at 48 weeks vs a 0.3% gain on placebo (GLORY-1, adults in China).
- EcnoglutideGLP-1
- Approved in ChinaApproved in China for type 2 diabetes in January 2026 and for weight in March 2026, and nowhere else. Weekly injection; a tablet is in development. Weight loss so far: 13.2% on 2.4 mg at 40 weeks vs a 0.1% gain on placebo (SLIMMER, 664 adults in China).
- MariTide (maridebart cafraglutide)An antibody that blocks the GIP receptor, carrying two GLP-1 peptides
- Phase 3Phase 3 (MARITIME) since March 2025; its two main weight trials are due to finish in early 2027. An injection every 4 weeks or less often. Weight loss so far: 12.3 to 16.2% at 52 weeks vs 2.5% on placebo (phase 2).
- VK2735GIP and GLP-1
- Phase 3Phase 3 (VANQUISH) since June 2025: two 78-week trials, fully enrolled, due to finish in mid-2027. Weekly injection; a tablet is in development. Weight loss so far: 14.7% on 15 mg at 13 weeks vs 1.7% on placebo (phase 2).
- EloralintideAmylin
- Phase 3Phase 3 (ENLIGHTEN) since December 2025. Weekly injection. Weight loss so far: Up to 20% at 48 weeks vs 0.4% on placebo, if everyone had stayed on treatment (phase 2, 263 adults).
- Amycretin (zenagamtide)GLP-1 and amylin, in one molecule
- Phase 3Phase 3 (AMAZE) since February 2026. Weekly injection or a daily tablet. Weight loss so far: 22.0% on 20 mg at 36 weeks vs a 1.9% gain on placebo, in an early trial of 125 people.
- PemvidutideGlucagon and GLP-1
- Phase 3Phase 3 in MASH, a fatty liver disease, since July 2026. Weekly injection. Weight loss so far: Its liver trial measured MASH, not weight: MASH cleared without worse scarring in 52 to 58% vs 20% on placebo at 24 weeks; scarring itself didn’t improve more than on placebo (IMPACT).
- PetrelintideAmylin
- Phase 3Phase 3 (ZUPREME) trials opened in September 2026. Weekly injection. Weight loss so far: Up to 9.8% at 28 weeks vs 1.7% on placebo, and up to 10.7% by week 42, if everyone had stayed on treatment (phase 2, 493 adults).
Registered trials of every compound, by phase: trials under way. Taking other peptides alongside a GLP-1 drug: every compound’s answer. Wegovy’s and Zepbound’s labels say not to combine them with another GLP-1 drug, and the stack check flags it.
Sources: Wegovy, Zepbound, Saxenda, Foundayo and Rybelsus prescribing information (2026); Mozaffarian et al., Nutritional priorities to support GLP-1 therapy for obesity, joint advisory (Am J Clin Nutr 2025), PMID 40450457; Look et al., body composition in SURMOUNT-1 (Diabetes Obes Metab 2025), PMID 39996356; Wilding et al., STEP 1 extension (Diabetes Obes Metab 2022), PMID 35441470; Rubino et al., STEP 4 (JAMA 2021), PMID 33755728; Wharton et al., STEP UP, semaglutide 7.2 mg (Lancet Diabetes Endocrinol 2025), PMID 40961952; Aronne et al., SURMOUNT-4 (JAMA 2024), PMID 38078870; Daneshgaran et al., “Ozempic face” systematic review (Aesthet Surg J Open Forum 2025), PMID 40626110; FDA, policies for compounders as GLP-1 supply stabilizes (content current April 1, 2026); FDA, concerns with unapproved GLP-1 drugs used for weight loss (content current October 1, 2026); FDA alert on dosing errors with compounded semaglutide (July 2024); Dahl et al., amycretin phase 1b/2a (Lancet 2025), PMID 40550231; Jastreboff et al., maridebart cafraglutide phase 2 (N Engl J Med 2025), PMID 40549887; Billings et al., eloralintide phase 2 (Lancet 2025), PMID 41207310; Bays et al., VK2735 VENTURE (Obesity 2026), PMID 41508550; Ji et al., ecnoglutide SLIMMER (Lancet Diabetes Endocrinol 2025), PMID 40555243; Shirley, ecnoglutide first approvals (Drugs 2026), PMID 42412371; Garvey et al., petrelintide ZUPREME 1 (Lancet Diabetes Endocrinol 2026), PMID 42810355; Noureddin et al., pemvidutide IMPACT (Lancet 2025), PMID 41237796; ClinicalTrials.gov records for the AMAZE, MARITIME, ENLIGHTEN, VANQUISH, ZUPREME and PERFORMA phase 3 trials (checked October 7, 2026); other weight-loss figures, filings and decisions from the GLP-1 class page and each compound’s page, where each is cited.