GLP-1 comparison tool: semaglutide vs tirzepatide vs liraglutide
Compare GLP-1 receptor agonists side by side: semaglutide vs tirzepatide vs liraglutide, evidence tiers, weight loss data, costs, and emerging research.
This tool compares FDA-approved prescription medications and research compounds. It is for educational purposes only and is not medical advice, a recommendation, or a substitute for professional healthcare guidance. GLP-1 receptor agonists are prescription drugs with significant side effects. Always consult a licensed physician before starting, stopping, or changing any medication.
The GLP-1 landscape in 2026
GLP-1 drugs differ most in how much weight they take off. In their pivotal trials, mean weight loss was about 15% for semaglutide (Wegovy), 20.9% for tirzepatide (Zepbound) at its top dose, 13.6% for the oral semaglutide 25 mg tablet, and 11.2% for orforglipron (Foundayo). Investigational retatrutide reached 24.2% in phase 2.
GLP-1 receptor agonists have transformed weight management and metabolic medicine. What started as diabetes drugs, liraglutide (Victoza, 2010) and semaglutide (Ozempic, 2017), has become the fastest-growing drug class in pharmaceutical history. The approvals of Wegovy (2021) and tirzepatide (Mounjaro, 2022; Zepbound, 2023) for chronic weight management opened a new era of incretin-based obesity treatment.
The core mechanism is straightforward: GLP-1 (glucagon-like peptide-1) is a natural hormone released by your gut after eating. It signals satiety to the brain, slows gastric emptying, and improves insulin sensitivity. Synthetic GLP-1 receptor agonists amplify and extend this signal far beyond what endogenous GLP-1 achieves, because the natural hormone is rapidly broken down by the enzyme DPP-4, which is why blocking that enzyme is itself a diabetes drug class[10].
But not all GLP-1 drugs are equal. They differ in mechanism (single vs dual vs triple agonist), route of administration (injection vs oral), dosing frequency (daily vs weekly), weight loss efficacy, side effect profiles, cardiovascular data, and cost. This tool helps you compare them objectively using data from major clinical trials.
Here is how each one did in its own pivotal trial. These are separate trials with different populations and durations, so read the column as a rough guide rather than a ranking; the head-to-head SURMOUNT-5 trial is covered in the next section.
| Drug (weight-loss brand) | Taken as | Mean weight loss vs placebo | Trial |
|---|---|---|---|
| Semaglutide (Wegovy) | Weekly injection | About 15% vs about 2% at 68 weeks | STEP 1 [1]. |
| Tirzepatide (Zepbound) | Weekly injection | 20.9% on the 15 mg dose vs 3.1% at 72 weeks | SURMOUNT-1 [2]. |
| Liraglutide (Saxenda) | Daily injection | 8.4 kg vs 2.8 kg at 56 weeks | SCALE [3]. |
| Oral semaglutide 25 mg | Daily tablet | 13.6% vs 2.2% at 64 weeks | OASIS 4 [11]. |
| Orforglipron (Foundayo) | Daily tablet | 11.2% on the top dose vs 2.1% at 72 weeks | ATTAIN-1 [14]. |
| Retatrutide (not approved) | Weekly injection | 24.2% on the 12 mg dose vs 2.1% at 48 weeks | Phase 2 [4]. |
What is the difference between semaglutide and tirzepatide?
Semaglutide (Ozempic, Wegovy) activates one hormone receptor, GLP-1, while tirzepatide (Mounjaro, Zepbound) activates two, GIP and GLP-1. Both are once-weekly injections. In SURMOUNT-5, which compared them head to head in adults with obesity but without type 2 diabetes, mean weight change at 72 weeks was -20.2% with tirzepatide and -13.7% with semaglutide.
The core difference is how many hormone receptors each drug switches on. Semaglutide is a glucagon-like peptide-1 receptor agonist[5]: it mimics one gut hormone. Tirzepatide is a glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 receptor agonist[2], so it acts on two incretin receptors at once. In their obesity trials both were given as a once-weekly subcutaneous injection[1][2].
The cleanest evidence on weight loss comes from SURMOUNT-5, which put the two drugs side by side instead of comparing separate trials. It randomized 751 adults with obesity but without type 2 diabetes to the maximum tolerated dose of tirzepatide or of semaglutide, once weekly for 72 weeks[15]. Mean weight change at week 72 was -20.2% with tirzepatide and -13.7% with semaglutide, and waist circumference fell by 18.4 cm against 13.0 cm[15]. The most common adverse events in both groups were gastrointestinal, mostly mild to moderate and concentrated in the dose-escalation period[15]. Two caveats belong next to those numbers: the trial was open-label, so participants knew which drug they were taking, and it was funded by Eli Lilly, which makes tirzepatide[15].
Where semaglutide still leads is cardiovascular evidence. SELECT tested it against placebo in people with obesity and existing heart disease but no diabetes and found a 20% relative reduction in major cardiovascular events[5]. Tirzepatide's cardiovascular trial compared it with another GLP-1 drug rather than with placebo, which the data section below explains.
FDA-approved vs research-only
Five GLP-1 drugs are now FDA-approved for weight management: semaglutide (Wegovy), liraglutide (Saxenda), tirzepatide (Zepbound), the oral semaglutide 25 mg tablet, and orforglipron (Foundayo). Retatrutide, a triple agonist, has the strongest weight loss data so far and is still investigational. Compounded versions are a different product from the approved one and are not covered by the trials here.
Three GLP-1 agonists have been approved for weight management for some time: semaglutide (Wegovy, injectable), liraglutide (Saxenda), and tirzepatide (Zepbound). Two oral options have now joined them. Oral semaglutide was the first oral GLP-1 approved for type 2 diabetes, and it is now approved for obesity management and cardiovascular risk reduction as well[9]. Orforglipron, the first non-peptide oral GLP-1 agonist, received its US approval in April 2026 for long-term weight management[8]. Retatrutide, a triple-agonist, has the highest weight loss data seen in any clinical programme to date and remains investigational rather than approved. Its phase 3 numbers are covered separately in the TRIUMPH-1 results.
Compounded semaglutide and tirzepatide were widely sold while the branded products were in shortage, and what a pharmacy may lawfully compound changes with that shortage status, so anything written here about availability dates quickly. Treat a compounded GLP-1 as a different product from the approved one: it has not been through the trials on this page, and the FDA has repeatedly flagged dosing errors and quality variability in that supply. Whether a particular product or pharmacy is appropriate is a question for a licensed clinician or pharmacist.
How to use this tool
Selecting two to three GLP-1 peptides below generates a live, side-by-side comparison: cards covering mechanism, evidence tier, FDA status, weight loss data, dosing, cost, pros, cons, and side effects; a bar chart of average trial weight loss; a radar chart scoring efficacy, convenience, tolerability, cost, and cardiovascular data; and a list of emerging compounds still in development.
Select 2-3 GLP-1 peptides below to generate a side-by-side comparison. The tool shows:
- Comparison cards: mechanism, evidence tier, FDA status, weight loss data, dosing, cost, pros, cons, and side effects
- Bar chart: average weight loss percentage from pivotal clinical trials
- Radar chart: multi-dimensional comparison across efficacy, evidence quality, convenience, tolerability, cost, and cardiovascular data
- Emerging research: next-generation compounds including BRP (Stanford's natural peptide), survodutide, and amycretin
Understanding the data
Each weight-loss figure traces to one trial: about 15% for semaglutide (STEP 1), 20.9% for tirzepatide (SURMOUNT-1), 24.2% for retatrutide in phase 2. Oral semaglutide appears at two doses, and the 25 mg weight-management tablet is the one to compare. Semaglutide leads on cardiovascular data because SELECT was placebo-controlled.
Weight loss percentages shown are averages from the highest-dose arms of pivotal trials, and each drug's figure traces to a specific study. Semaglutide's comes from the STEP 1 trial, about 15% mean loss at 68 weeks versus roughly 2% with placebo[1]. Tirzepatide's comes from SURMOUNT-1, 20.9% mean loss at 72 weeks on the highest dose[2]. Liraglutide's comes from the earlier SCALE trial[3], and retatrutide's 24.2% at 48 weeks is the phase 2 figure[4]. Its phase 3 programme has since reported, and those numbers are covered in the TRIUMPH-1 results. It remains investigational rather than approved. Oral semaglutide's two numbers are two different doses, not two different drugs. PIONEER 1, the trial behind the diabetes approval, tested 14 mg and its highest dose gave about 2.6 kg more weight loss than placebo over 26 weeks in people with type 2 diabetes[6]. The 25 mg tablet approved for weight management gave 13.6% against 2.2% on placebo at week 64 in OASIS 4[11], which is the figure to set beside the injectable. Individual results vary significantly based on genetics, diet, exercise, adherence, and starting weight, and these trials also layered in structured lifestyle counseling that contributed to the outcomes.
The radar chart scores are derived from published trial data and clinical guidelines. The "cardiovascular data" axis reflects whether a compound has dedicated cardiovascular outcomes trial (CVOT) data showing benefit. Semaglutide scores highest here because the SELECT trial found a 20% relative reduction in major cardiovascular events in people with obesity and existing heart disease but no diabetes[5]. Tirzepatide's cardiovascular trial asked a different question. SURPASS-CVOT compared it against dulaglutide, an active drug rather than a placebo, in people with type 2 diabetes and atherosclerotic disease, and tirzepatide was noninferior for three-point major adverse cardiovascular events while delivering greater metabolic and renal benefit[12]. Noninferior to another GLP-1 is not the same claim as SELECT's reduction against placebo, and the two numbers should not be read as if they were.
Cost bands in the tool are indicative only and go stale quickly: what you actually pay depends on formulary tier, manufacturer savings programmes and direct-to-patient pricing far more than on any list price. Retatrutide is listed as "not yet available" because it has not received FDA approval.
How to read the comparison without overfitting
The highest number on a weight-loss chart is not automatically the right choice: tolerability, contraindications, access, dose-escalation speed, and the ability to maintain protein intake can matter as much as headline efficacy, and a slightly weaker performer may win in the real world if it is easier to stay on. Trial averages also hide a wide individual spread in outcomes.
The strongest drug on a weight-loss chart is not automatically the best fit for every person. Tolerability, contraindications, access, dose escalation speed, and ability to maintain protein intake can matter as much as headline efficacy. A compound that looks slightly weaker in trials may be the better real-world option if it is easier to stay on consistently.
Trial averages also hide the spread. Some participants lose far more than the mean, some lose much less, and some stop because of side effects. That is why the tool keeps efficacy, convenience, tolerability, cardiovascular data, and cost as separate axes instead of collapsing everything into one winner.
Want the full picture on Retatrutide?
The Retatrutide mastery course covers the mechanism, the evidence, and how to read a protocol.
What to compare before switching
Before switching GLP-1 drugs, separate the real trigger, plateau, nausea, access problems, or inadequate appetite control, from behavior drift like lower protein intake or missed doses. Use a comparison to prepare for a clinician conversation, not replace one, since it cannot weigh your full medical history, and plan the off-ramp, not just the switch, before committing to a change.
Before changing from one GLP-1 pathway drug to another, compare the reason you are considering the switch. Plateau, nausea, access problems, and inadequate appetite control point to different decisions. Also separate medication effect from behavior drift: lower protein intake, reduced resistance training, and missed doses can mimic a pharmacology problem.
For any prescription medication decision, use the comparison as a preparation tool for a clinician conversation. It can organize the evidence and tradeoffs, but it cannot evaluate your full medical history, other medications, gallbladder risk, pregnancy plans, or diabetes treatment plan.
Also compare the off-ramp. Some people use these medications for chronic disease management, while others expect a finite course. Maintenance planning changes the answer: muscle retention, food environment, follow-up frequency, and what happens after dose reduction are part of the real comparison even though they rarely appear in simple drug-versus-drug tables. The tirzepatide plateau and off-ramp guide addresses the muscle-preservation and dose-tapering questions that most comparison tools skip, and the CagriSema REDEFINE-1 analysis covers the next combination approach, which has since been filed with the FDA.
Frequently asked questions
Semaglutide (Ozempic, Wegovy) is a GLP-1 receptor agonist[5], while tirzepatide (Mounjaro, Zepbound) activates two receptors, GIP and GLP-1[2]. Both are once-weekly injections. In SURMOUNT-5, the head-to-head trial in adults with obesity but without type 2 diabetes, mean weight change at 72 weeks was -20.2% with tirzepatide and -13.7% with semaglutide[15]. Semaglutide has the placebo-controlled cardiovascular outcome data, from SELECT[5].
Among approved drugs, tirzepatide. It produced 20.9% mean weight loss on its top dose in SURMOUNT-1[2], and in the head-to-head SURMOUNT-5 trial it beat semaglutide, -20.2% against -13.7% at 72 weeks[15]. Retatrutide reached 24.2% at 48 weeks in phase 2[4], but it is still investigational. Weight loss is only one axis: semaglutide is the one with placebo-controlled cardiovascular outcome data[5].
For weight loss alone, the head-to-head evidence favours tirzepatide. In SURMOUNT-5, an open-label trial in adults with obesity but without type 2 diabetes, tirzepatide was superior to semaglutide for reduction in body weight and waist circumference at week 72, with mean weight change of -20.2% against -13.7%[15]. Semaglutide, however, has proven cardiovascular benefit against placebo from the SELECT trial[5]. The "better" option depends on individual health profile, tolerability, insurance coverage, and prescriber assessment.
Retatrutide is a triple-agonist peptide from Eli Lilly that simultaneously activates GIP, GLP-1, and glucagon receptors. The glucagon receptor component is proposed to add energy expenditure and liver fat oxidation on top of what dual agonists like tirzepatide do. In phase 2 trials, it showed up to 24.2% weight loss at 48 weeks. Its phase 3 programme has reported since, covered separately in the TRIUMPH-1 write-up, and it is not FDA-approved.
Compounded semaglutide and tirzepatide were widely sold while the branded products were in shortage, and what a pharmacy may lawfully compound changes with that shortage status, so availability information dates quickly. A compounded GLP-1 is a different product from the approved one: it has not been through the trials on this page, and the FDA has repeatedly flagged dosing errors and quality variability in that supply. Whether a particular source is lawful or appropriate is a question for a licensed clinician and pharmacist, not a comparison tool.
There are now two FDA-approved oral GLP-1 options. Oral semaglutide arrived first, as Rybelsus for type 2 diabetes, and the 25 mg tablet is now approved for obesity management and cardiovascular risk reduction too[9]. It uses a SNAC absorption enhancer and must be taken on an empty stomach with minimal water, 30 minutes before food. Read its weight-loss number carefully, because two different doses get quoted as one. PIONEER 1, the trial behind the diabetes approval, tested 14 mg and its highest dose produced about 2.6 kg more weight loss than placebo over 26 weeks[6]. The tablet approved for weight management is 25 mg, and in OASIS 4 that dose produced a 13.6% body weight reduction against 2.2% on placebo[11], in the same range as injectable semaglutide rather than a fraction of it. Orforglipron, a non-peptide oral GLP-1 agonist from Eli Lilly, was approved in the United States as Foundayo in April 2026 for long-term weight management[8]. Because it is not a peptide it carries none of the strict empty-stomach rules. Its approval rests on the ATTAIN-1 phase 3 trial, which reported 11.2% at the top dose against 2.1% on placebo at 72 weeks[14]; the earlier phase 2 figure of up to 14.7%[7] is the one still widely quoted.
BRP (BRINP2-related peptide) is a naturally occurring 12-amino-acid peptide discovered by Stanford researchers. Unlike synthetic GLP-1 agonists, BRP appears to regulate body weight through a novel, GLP-1-independent pathway. In mouse studies, it reduced body weight without the nausea and GI side effects common to GLP-1 drugs. It is still in very early preclinical research and is not available as a treatment.
List prices move faster than any article can, and what you pay is set mostly by things that are not the list price: insurance formulary tier, manufacturer savings programmes, direct-to-patient pricing from the manufacturers themselves, and pharmacy discount cards. Check the manufacturer site and your own formulary for a current figure rather than trusting a number quoted in an article, including this one.
References
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- Jastreboff AM, Aronne LJ, Ahmad NN, et al. "Tirzepatide Once Weekly for the Treatment of Obesity." N Engl J Med. 2022. PMID 35658024 DOI
- Pi-Sunyer X, Astrup A, Fujioka K, et al. "A Randomized, Controlled Trial of 3.0 mg of Liraglutide in Weight Management." N Engl J Med. 2015. PMID 26132939 DOI
- Jastreboff AM, Kaplan LM, FrÃas JP, et al. "Triple-Hormone-Receptor Agonist Retatrutide for Obesity - A Phase 2 Trial." N Engl J Med. 2023. PMID 37366315 DOI
- Lincoff AM, Brown-Frandsen K, Colhoun HM, et al. "Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes." N Engl J Med. 2023. PMID 37952131 DOI
- Aroda VR, Rosenstock J, Terauchi Y, et al. "PIONEER 1: Randomized Clinical Trial of the Efficacy and Safety of Oral Semaglutide Monotherapy in Comparison With Placebo in Patients With Type 2 Diabetes." Diabetes Care. 2019. PMID 31186300 DOI
- Wharton S, Blevins T, Connery L, et al. "Daily Oral GLP-1 Receptor Agonist Orforglipron for Adults with Obesity." N Engl J Med. 2023. PMID 37351564 DOI
- Shirley M. "Orforglipron: First Approval." Drugs. 2026. PMID 42479349 DOI
- Rubino D, Wharton S, Knight MG, Aroda VR. "Evidence-informed guidance for the clinical use of oral semaglutide in obesity management." Postgrad Med. 2026. PMID 42286992 DOI
- Kahles F, Birkenfeld AL, Marx N. "GLP-1 and the cardiovascular system." J Clin Invest. 2026. PMID 41697744 DOI
- Wharton S, Lingvay I, Bogdanski P, et al. "Oral Semaglutide at a Dose of 25 mg in Adults with Overweight or Obesity." N Engl J Med. 2025. PMID 40934115
- Busti M, Canonico ME, Keramida K, et al. "Tirzepatide versus dulaglutide in heart failure: another SURPASS attempt yielding a tie." Heart Fail Rev. 2026. PMID 41984352
- Damen JAA, Idema DL, Vernooij RWM, et al. "Benefits and Harms of Pharmacologic Treatments in Adults With Overweight or Obesity: A Living Systematic Review." Ann Intern Med. 2026. PMID 42296503
- Wharton S, Aronne LJ, Stefanski A, et al. "Orforglipron, an Oral Small-Molecule GLP-1 Receptor Agonist for Obesity Treatment." N Engl J Med. 2025. PMID 40960239
- Aronne LJ, Horn DB, le Roux CW, et al. "Tirzepatide as Compared with Semaglutide for the Treatment of Obesity." N Engl J Med. 2025. PMID 40353578 DOI