GLP-1 peptides compared in plain English
How semaglutide, tirzepatide, liraglutide, and investigational retatrutide differ in targets, evidence, and approval status.
Published by PeptideFactSheets. Sources and methods · Research reporting, not clinical review.
Cardiovascular outcomes: who was studied?
SELECT and LEADER each compared an active treatment with placebo. Their diabetes criteria and baseline risks differ. They are not a head-to-head trial.
| Study and people | Question and follow-up | Result and limits |
|---|---|---|
| SELECT Age 45+, established cardiovascular disease, BMI ≥27, no diabetes 17,604 participants (actual) Randomized placebo-controlled trial; human | Semaglutide versus Placebo Mean follow-up 39.8 months Primary: First cardiovascular death, nonfatal heart attack or nonfatal stroke Phase: Not listed in this summary | 569/8803 (6.5%) versus 701/8801 (8.0%) had a primary event. 1.5 percentage points fewer events, using rounded published proportions. Hazard ratio 0.80; 95% CI 0.72–0.90. A hazard ratio is not a risk ratio. Cannot tell us: A secondary-prevention population; not a trial in healthy adults or a head-to-head comparison. Safety, uncertainty, and source detailsDiscontinuation due to adverse events: 16.6% versus 8.2%. Limited to the studied population, formulation and follow-up. Funding/conflicts: Funded by Novo Nordisk; individual disclosures not fully extracted. Source checked: 2026-09-18. Independent clinical review: not completed. |
| LEADER Type 2 diabetes and high cardiovascular risk 9,340 participants (actual) Randomized placebo-controlled trial; human | Liraglutide versus Placebo Median follow-up 3.8 years Primary: First cardiovascular death, nonfatal heart attack or nonfatal stroke Phase: Not listed in this summary | 608/4668 (13.0%) versus 694/4672 (14.9%) had a primary event. 1.9 percentage points fewer events, using rounded published proportions. Hazard ratio 0.87; 95% CI 0.78–0.97. Cannot tell us: Population differs from SELECT; these two placebo comparisons cannot rank liraglutide against semaglutide. Safety, uncertainty, and source detailsGastrointestinal events most commonly led to discontinuation. Limited to the studied population, formulation and follow-up. Funding/conflicts: Novo Nordisk and NIH; individual disclosures not fully extracted. Source checked: 2026-09-18. Independent clinical review: not completed. |
Why this comparison cannot rank treatments
We align reported populations, primary outcomes, duration and uncertainty. We do not pool studies or adjust for differences in baseline risk. An indirect comparison is a research-reading exercise, not a statistical estimate of comparative effectiveness. Registry results, published papers and regulatory decisions are checked separately. When a detail has not been confirmed, we say so.
Weight studies: published results versus registered comparisons
SURMOUNT-1 and the retatrutide Phase 2 study were separate placebo comparisons. TRIUMPH-5 is a registered direct comparison; its record does not yet contain results at the source check.
| Study and people | Question and follow-up | Result and limits |
|---|---|---|
| SURMOUNT-1 Adults with obesity or overweight plus a complication; diabetes excluded 2,539 participants (actual) Randomized placebo-controlled trial; human | Tirzepatide versus Placebo 72 weeks Primary: Percentage weight change and proportion reaching at least 5% reduction Phase: Phase 3 | Active groups had greater mean weight reduction than placebo. Cannot tell us: Weight change alone does not quantify cardiovascular-event or survival benefit; different active regimens are not pooled here. Safety, uncertainty, and source detailsGastrointestinal events were most common; adverse events led to discontinuation in both active and placebo groups. Limited to the studied population, formulation and follow-up. Funding/conflicts: Supported by Eli Lilly; individual disclosures not fully extracted. Source checked: 2026-09-18. Independent clinical review: not completed. |
| Retatrutide Phase 2 Adults with obesity or overweight plus a weight-related condition 338 participants (actual) Randomized placebo-controlled trial; human | Retatrutide versus Placebo 48 weeks; primary endpoint at 24 weeks Primary: Percentage body-weight change at week 24 Weight change at week 48 was secondary, not the primary endpoint. Phase: Phase 2 | Greater weight reductions than placebo were reported. Cannot tell us: A Phase 2 result is neither approval nor a direct comparison with semaglutide or tirzepatide. Safety, uncertainty, and source detailsGastrointestinal events and increases in heart rate were reported. Limited to the studied population, formulation and follow-up. Funding/conflicts: Funded by Eli Lilly; individual disclosures not fully extracted. Source checked: 2026-09-18. Independent clinical review: not completed. |
| TRIUMPH-5 Adults with obesity 800 participants (estimated) Randomized placebo-controlled trial; human | Retatrutide versus Tirzepatide Primary weight endpoint: 80 weeks Primary: Percentage body-weight change Phase: Phase 3 | Active, not recruiting; no registry results posted at the source check. Cannot tell us: A registered head-to-head design is not a completed head-to-head result. Enrollment is estimated. Safety, uncertainty, and source detailsSee primary paper; absence of a signal in this study does not establish general safety. Limited to the studied population, formulation and follow-up. Funding/conflicts: Sponsor: Eli Lilly and Company. Source checked: 2026-09-18. Independent clinical review: not completed. |
Why this comparison cannot rank treatments
We align reported populations, primary outcomes, duration and uncertainty. We do not pool studies or adjust for differences in baseline risk. An indirect comparison is a research-reading exercise, not a statistical estimate of comparative effectiveness. Registry results, published papers and regulatory decisions are checked separately. When a detail has not been confirmed, we say so.
The quick overview
“GLP-1” is a useful family label, not a promise that every medicine works the same way. Liraglutide and semaglutide act at the GLP-1 receptor; tirzepatide acts at GIP and GLP-1 receptors; retatrutide is designed to act at GIP, GLP-1, and glucagon receptors.
Semaglutide, tirzepatide, and liraglutide appear in FDA-approved products for specific uses. Retatrutide remains investigational, even with a completed Phase 3 registry record and company-reported top-line results. Evidence and safety must be read at the product-and-indication level, not inferred from the family name.
Side-by-side comparison
| Peptide | Status | Evidence | Studied for |
|---|---|---|---|
| Semaglutide | FDA approved for specific uses | Strong human evidence for approved uses | Type 2 diabetes; Chronic weight management; Cardiovascular outcomes |
| Tirzepatide | FDA approved for specific uses | Strong human evidence for approved uses | Type 2 diabetes; Chronic weight management; Obstructive sleep apnea in adults with obesity |
| Liraglutide | FDA approved for specific uses | Strong human evidence for approved uses | Type 2 diabetes; Chronic weight management; Cardiovascular outcomes |
| Retatrutide | In clinical trials | Moderate human evidence | Obesity and overweight; Type 2 diabetes; Cardiovascular and kidney outcomes |
Studied for
Type 2 diabetes · Chronic weight management · Cardiovascular outcomes
Studied for
Type 2 diabetes · Chronic weight management · Obstructive sleep apnea in adults with obesity
Studied for
Type 2 diabetes · Chronic weight management · Cardiovascular outcomes
Studied for
Obesity and overweight · Type 2 diabetes · Cardiovascular and kidney outcomes
Approved versus investigational
An FDA approval means the agency reviewed evidence for a specific product, population, and use. It does not validate other molecules in the same family or uses outside the label. “In Phase 3” still means investigational.
What researchers are studying
- Blood-sugar control in type 2 diabetes
- Chronic weight management
- Cardiovascular and kidney outcomes
- Obesity-related conditions such as obstructive sleep apnea
Risks and reasons for caution
- All can cause adverse effects; approved labels include medicine-specific warnings, contraindications, and use limitations.
- A larger average change in one trial is not a head-to-head answer unless populations, study designs, duration, and endpoints are comparable.
- Compounded or online products are not made equivalent merely by using the name of an approved active ingredient.
What remains uncertain
- How every option compares head-to-head for long-term outcomes
- Which results will extend to populations not represented in trials
- The final benefit-risk profile and regulatory future of retatrutide
Questions to ask a healthcare professional
1. Which exact product and approved indication are we discussing?
2. What benefits were measured in people like me, and over what period?
3. Which warnings, interactions, or conditions change the risk?
4. What follow-up is needed to assess benefit and adverse effects?
Plain-English takeaway
The most important difference is not which name is newest. It is whether the exact product is approved for the exact use, what human evidence supports it, and how its risks fit a particular patient under licensed care.
Related comparisons
References
- 1fdaFDA prescribing information: Wegovy
Current semaglutide label covering approved weight, cardiovascular-risk, and MASH indications.
- 2fdaFDA prescribing information: Zepbound
Current tirzepatide label covering chronic weight management and obstructive-sleep-apnea indications.
- 3fdaFDA prescribing information: Saxenda
Current liraglutide label for chronic weight management in defined populations.
- 4clinical trialsClinicalTrials.gov: TRIUMPH-1
Completed Phase 3 retatrutide registry record without posted ClinicalTrials.gov results.
- 5company releaseLilly: TRIUMPH-1 top-line results
Company-provided Phase 3 top-line obesity results; not a peer-reviewed publication or FDA approval.
- 6pubmedRetatrutide Phase 2 obesity trial
Peer-reviewed Phase 2 evidence for the investigational triple-agonist program.