GLP-1 Medications Compared: Semaglutide vs Tirzepatide vs Retatrutide
5 major incretin medications are FDA-approved; the newest triple- and dual-agonists remain investigational. Here is the honest comparison — by class, FDA status, weight-loss trial results, and side effects. No brand names, no doses, no hype.
Medically reviewed by Charles Kamen, MD, board-certified neurologist ·
Semaglutide, tirzepatide, liraglutide, dulaglutide, and exenatide are FDA-approved incretin medications; retatrutide, survodutide, and CagriSema remain investigational. They differ by how many incretin pathways they activate. Semaglutide, liraglutide, dulaglutide, and exenatide are single GLP-1 receptor agonists. Tirzepatide is a dual GIP/GLP-1 agonist. Retatrutide is a triple GIP/GLP-1/glucagon agonist. More pathways does not always mean more is appropriate for you — but it is the core reason the newer agents produce larger mean weight loss in trials (Müller et al., 2019; Jastreboff et al., 2023).
GLP-1 (glucagon-like peptide 1) is an incretin hormone that slows stomach emptying, signals satiety to the brain, and supports insulin release after eating. GLP-1 receptor agonists mimic that hormone to reduce appetite and, in the approved agents, support weight management and glucose control. The physiology behind these effects is reviewed in Müller et al. (Mol Metab, 2019).
Weight-loss figures below are trial results, not guaranteed outcomes. They are reported as group means in published studies and attributed to those citations. Individual response depends on adherence, nutrition, activity, and tolerability, and is reviewed against your own data over time.
The comparison
Drug class, FDA approval status, what each is approved or studied for (with year), administration form, and weight-loss trial result. Generic names only.
| Medication | Class / receptors | FDA status | Approved / studied for | Weight-loss range (trial) | Form |
|---|---|---|---|---|---|
| Semaglutide | GLP-1 receptor agonist | FDA-approved | Type 2 diabetes (2017); chronic weight management (2021); cardiovascular event risk reduction in adults with obesity and established cardiovascular disease (2024); major adverse cardiovascular event reduction in type 2 diabetes (2025). | Around 15% mean body-weight loss at the studied maintenance injection in the STEP 1 trial (Wilding et al., 2021). | Injection; oral tablet |
| Tirzepatide | Dual GIP / GLP-1 receptor agonist | FDA-approved | Type 2 diabetes (2022); chronic weight management (2023); moderate-to-severe obstructive sleep apnea in adults with obesity (2024) — the first medication ever FDA-approved for OSA. | Reported at roughly 20–22.5% mean weight loss at the studied maintenance injection in registrational obesity trials; ranked ahead of semaglutide in head-to-head network meta-analyses (PMC12544991, 2025). | Injection |
| Liraglutide | GLP-1 receptor agonist | FDA-approved | Type 2 diabetes (2010); chronic weight management (2014); cardiovascular risk reduction in type 2 diabetes. | Around 8% mean weight loss at the studied daily maintenance dose in obesity trials — less than the newer weekly agents. | Daily injection |
| Dulaglutide | GLP-1 receptor agonist | FDA-approved | Type 2 diabetes (2014); cardiovascular event risk reduction in adults with type 2 diabetes. | Modest weight loss as a secondary outcome; approved for glucose and cardiovascular risk reduction rather than weight management. | Weekly injection |
| Exenatide | GLP-1 receptor agonist (first in class) | FDA-approved | Type 2 diabetes (2005; extended-release 2012). The first FDA-approved GLP-1 receptor agonist. | Modest weight loss as a secondary outcome in type 2 diabetes trials. | Injection (twice-daily and weekly extended-release) |
| Retatrutide | Triple GIP / GLP-1 / glucagon receptor agonist | Investigational | Studied for obesity and type 2 diabetes in the Phase 3 TRIUMPH program. Not FDA-approved as of the review date; not available outside clinical trials. | Up to about 24% mean weight loss at the highest studied dose in a Phase 2 trial (Jastreboff et al., 2023); Phase 3 topline figures have reported in the ~28–30% range. Investigational — not an approved or available medication. | Injection (in trials) |
| Survodutide | Dual glucagon / GLP-1 receptor agonist | Investigational | Studied for weight management and metabolic dysfunction-associated steatohepatitis (MASH). Not FDA-approved. | Mean weight loss reported in the ~19% range at the studied maintenance dose in Phase 2 obesity data; investigational only. | Injection (in trials) |
| CagriSema | Amylin analog (cagrilintide) + GLP-1 receptor agonist (semaglutide) | Investigational | Studied for weight management. An FDA application was submitted in late 2025; not yet approved as of the review date. | Mean weight loss reported below earlier projections in the registrational program; investigational only. | Injection (in trials) |
How this comparison is maintained: compiled and reviewed by Charles Kamen, MD from FDA approval records and the cited trials. Approval years reflect the first FDA approval for the listed indication; some products carry additional later indications. Weight-loss ranges are group means at the studied maintenance level in the cited registrational or Phase 2 program and are not individual predictions. Investigational-agent timelines reflect publicly announced filings and are not FDA approvals — verify current status at the time of care.
Educational reference, not medical advice. This page does not recommend a specific medication or state that any drug treats, cures, or prevents a disease, and it publishes no doses or titration schedules. Whether any GLP-1 medication is appropriate is a decision for you and a licensed clinician.
Side effects, muscle loss, and what to watch
The most common side effects across GLP-1 receptor agonists are gastrointestinal — nausea, vomiting, diarrhea, constipation, and reduced appetite — and tend to be most noticeable early. Less common but serious risks include pancreatitis, gallbladder issues, and kidney injury related to dehydration from persistent vomiting. These outcomes follow directly from GLP-1 physiology (Müller et al., 2019), which is why these medications require physician supervision rather than self-direction.
A portion of the weight lost on incretin medications can be lean mass, not only fat. This is a recognized concern with high-magnitude weight loss of any kind. A physician-led plan addresses it with adequate protein intake, resistance training where appropriate, and follow-up body-composition monitoring — weight loss without context is not the goal.
GLP-1 Medication FAQ
Which GLP-1 medication is best for weight loss?
Among FDA-approved incretin medications, the dual GIP/GLP-1 agonist tirzepatide has produced the largest mean weight loss in registrational obesity trials — roughly 20–22.5% at the studied maintenance injection. The single-pathway GLP-1 agonist semaglutide reached around 15% in its STEP 1 trial. Which medication is appropriate for a given person is a clinical decision based on history, goals, and tolerance, not a ranking. Individual results vary and are not guaranteed.
What is the difference between semaglutide and tirzepatide?
Semaglutide activates one pathway — the GLP-1 receptor. Tirzepatide activates two — GIP and GLP-1. That extra pathway is the main reason tirzepatide has produced larger mean weight loss in head-to-head network comparisons. Tirzepatide is also the only incretin medication FDA-approved for moderate-to-severe obstructive sleep apnea in adults with obesity. Both are FDA-approved for chronic weight management and for type 2 diabetes.
Is retatrutide FDA-approved?
No. Retatrutide is investigational as of the review date. It is a triple GIP/GLP-1/glucagon receptor agonist being studied in the Phase 3 TRIUMPH program. It is not FDA-approved and is not available outside clinical trials. Anyone offering retatrutide for sale before approval is doing so outside the regulatory pathway — do not buy it.
Which GLP-1 medication is the strongest?
In head-to-head network meta-analyses, the triple agonist retatrutide has produced the largest mean weight loss of any incretin studied so far — but it is not approved or available. Among approved medications, the dual agonist tirzepatide has produced larger mean weight loss than the single-pathway GLP-1 agonists semaglutide and liraglutide. Strongest is not the same as best for you: the right choice depends on medical history, tolerability, and indication.
What are the common side effects of GLP-1 medications?
The most common side effects across GLP-1 receptor agonists are gastrointestinal: nausea, vomiting, diarrhea, constipation, and reduced appetite, typically most noticeable early and as the body adjusts. Less common but serious risks include pancreatitis, gallbladder issues, and — in rare case reports — kidney injury related to dehydration from persistent vomiting. GLP-1 physiology and the satiety and metabolism effects behind these outcomes are reviewed in Müller et al. (Mol Metab, 2019). Side-effect risk is part of why these medications require physician supervision.
How much does a GLP-1 evaluation cost in Las Vegas?
Care at LiveNow Longevity starts with an $88 physician evaluation with board-certified neurologist Dr. Charles Kamen, MD — applied toward your plan if you continue. From there, cost depends on the labs and any protocol appropriate for you. Every line item is reviewed with you before you commit. There is no subscription and no hidden markup.
Can I get a GLP-1 medication through telehealth in Nevada?
Yes. Nevada residents can complete the evaluation and follow-ups by secure telehealth, with labs drawn at a location near you. In-person visits are available at our southeast Las Vegas clinic at Eastern Ave and the 215. A GLP-1 medication is only prescribed after a real medical evaluation and labs confirm it is appropriate for you — never as a one-click checkout.
Do GLP-1 medications cause muscle loss?
A meaningful share of the weight lost on incretin medications can be lean mass, not just fat. This is an active area of research and a recognized concern with high-magnitude weight loss of any kind. A physician-led plan addresses this with adequate protein intake, resistance training where appropriate, and follow-up body-composition monitoring rather than weight loss in a vacuum.
Can I get GLP-1 care near me — Henderson or Summerlin?
Yes. LiveNow Longevity serves Las Vegas, Henderson, Summerlin, Green Valley, and all of Nevada — in person at our southeast Las Vegas clinic at Eastern Ave and the 215, or by secure telehealth for Nevada residents. If you are searching for GLP-1 or weight-management care near you in the Las Vegas valley, start with the $88 evaluation.
How long does it take to see results from a GLP-1 medication?
In registrational trials, weight loss with semaglutide and tirzepatide was gradual and continued over many months rather than appearing in the first few weeks. Individual response varies and depends on adherence, nutrition, activity, and whether the medication is tolerated. We track weight and relevant biomarkers against your own baseline over time so progress is measured, not assumed.
Which GLP-1 medication is FDA-approved for sleep apnea?
Only tirzepatide is FDA-approved for sleep apnea — approved in 2024 for moderate-to-severe obstructive sleep apnea in adults with obesity, the first medication ever FDA-approved for OSA. None of the other incretin medications carry this indication.
Which is the oldest GLP-1 drug?
Exenatide is the oldest GLP-1 drug — the first-in-class GLP-1 receptor agonist, FDA-approved in 2005 for type 2 diabetes. The class has since expanded to dual (tirzepatide) and investigational triple (retatrutide) receptor agonists.
Looking for GLP-1 care rather than a comparison? GLP-1 weight loss in Las Vegas covers how to get physician-prescribed semaglutide or tirzepatide locally after an $88 evaluation.
Related reading: Semaglutide vs tirzepatide vs retatrutide · Which peptides are FDA-approved? · Is compounded tirzepatide the same as branded tirzepatide? · Peptide drug-class taxonomy · Peptide evidence-grade index
Selected Research
- Müller TD, et al. Mol Metab. 2019;30:72-130. (Glucagon-like peptide 1 (GLP-1): physiology, satiety, and metabolism).
- Wilding JPH, et al. N Engl J Med. 2021;384(11):989-1002. (STEP 1: once-weekly semaglutide for overweight/obesity).
- Jastreboff AM, et al. N Engl J Med. 2023;389(6):514-526. (Triple-hormone-receptor agonist retatrutide for obesity — a phase 2 trial).
- Comparative efficacy and safety of tirzepatide vs retatrutide in weight loss: a network meta-analysis. J Endocr Soc. 2025. (PMC12544991).
Mechanism and trial-result sources only. Not a treatment claim. Individual results vary; protocols are individualized after medical evaluation.
Physician-Led in Las Vegas
Weighing your options?
A board-certified neurologist will explain how these medications differ, what is FDA-approved, and whether a GLP-1 medication fits your history and goals — in person in Las Vegas or by secure telehealth for Nevada residents. Start with the $88 evaluation.
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