GLP-1 Medications Comparison: Complete Guide & Chart

## Choosing Between GLP-1 Medications: What the Clinical Data Actually Shows If you have spent any time researching weight loss medications, you have probably encountered a confusing alphabet soup: GLP-1, GIP, Semaglutide, Tirzepatide, Retatrutide. Which one produces the best results? Which has the fewest side effects? And which makes sense for your specific situation? We reviewed data from every major clinical trial published through January 2026 -- including the landmark STEP, SURMOUNT, and Retatrutide phase 2 programs -- to build this head-to-head comparison. Rather than repeating marketing claims, we focus on what the peer-reviewed evidence actually demonstrates. ## The Four Major GLP-1 Medications at a Glance A 2024 network meta-analysis in *The Lancet Diabetes & Endocrinology* compared GLP-1 receptor agonists across 28 randomized controlled trials. Here is how the leading options stack up: | Feature | Semaglutide | Tirzepatide | Retatrutide | Liraglutide | |---------|-------------|-------------|-------------|-------------| | **Mechanism** | GLP-1 | GLP-1 + GIP | GLP-1 + GIP + Glucagon | GLP-1 | | **Dosing** | Weekly | Weekly | Weekly | Daily | | **Max Dose** | 2.4mg | 15mg (FDA) | 12mg (trial) | 3mg | | **Avg Weight Loss** | 15-17% | 20-22% | 22-24% | 8-10% | | **FDA Approved** | Yes | Yes | Phase 3 | Yes | | **Oral Option** | Yes (Rybelsus) | No | No | No | ## Semaglutide (Ozempic / Wegovy): The Proven Standard Semaglutide was the medication that transformed obesity treatment from a niche specialty into mainstream medicine. The STEP trial program, published in *The New England Journal of Medicine* in 2021, demonstrated an average 14.9% body weight reduction at 68 weeks -- a result that made international headlines. What makes Semaglutide stand out in March 2026 is not raw efficacy (newer drugs exceed it) but rather the depth of evidence behind it. The SELECT cardiovascular outcomes trial (NEJM, 2023) showed a 20% reduction in major adverse cardiovascular events among patients with existing heart disease -- data that no other GLP-1 in this class has yet matched. For patients with cardiovascular risk factors, that finding alone can tip the decision. **Dosing schedule:** Start at 0.25mg weekly, escalating every 4 weeks through 0.5mg, 1mg, and 1.7mg, up to a maximum of 2.4mg for weight management. **Who should consider it:** First-time GLP-1 users, patients who value an extensive safety track record, those with cardiovascular concerns, and anyone seeking the most affordable compounded option. Compounded Semaglutide typically runs $200-400 per month compared to $935+ for brand Ozempic. ## Tirzepatide (Mounjaro / Zepbound): The Efficacy Leader Tirzepatide changed the game by targeting two receptors instead of one. The SURMOUNT-1 trial (*NEJM*, 2022) showed participants on 15mg Tirzepatide lost an average of 22.5% of their body weight at 72 weeks -- roughly 5 percentage points more than Semaglutide achieves. Approximately one-third of participants lost over 25% of their starting weight, a threshold previously achievable only through bariatric surgery. The dual GIP/GLP-1 mechanism appears to enhance insulin sensitivity and fat oxidation beyond what GLP-1 alone provides. For patients with type 2 diabetes, Tirzepatide produces A1C reductions of 2.0-2.5%, the strongest glycemic improvement in the class. **Dosing schedule:** Start at 2.5mg weekly, escalating every 4 weeks through 5mg, 7.5mg, 10mg, 12.5mg, up to 15mg (FDA approved). Compounded versions are available at higher doses. **Who should consider it:** Patients seeking maximum weight loss, those with type 2 diabetes who need aggressive A1C reduction, and anyone who can tolerate a newer medication with somewhat less long-term data. Compounded Tirzepatide typically costs $250-500 per month. ## Retatrutide: The Triple-Threat Newcomer Retatrutide represents the next evolutionary leap in metabolic medicine. By targeting three receptors simultaneously -- GLP-1, GIP, and glucagon -- it attacks obesity through mechanisms that single and dual agonists cannot access. The glucagon component increases energy expenditure, meaning you burn more calories even at rest. The phase 2 trial published in *NEJM* (2023) reported weight loss of up to 24.2% at 48 weeks at the 12mg dose, with some participants losing over 27%. These are the highest numbers ever recorded for a pharmaceutical weight loss intervention. Phase 3 trials are currently underway, with results expected in 2026-2027. **Current status:** Not FDA approved. Available through compounding pharmacies under provider supervision. Phase 3 data will determine the regulatory timeline. **Who should consider it:** Patients who have plateaued on Semaglutide or Tirzepatide, those seeking the highest available efficacy, early adopters comfortable with a medication still in trials, and always under close medical supervision. ## Liraglutide (Saxenda / Victoza): The Established Veteran Liraglutide was the first GLP-1 approved for weight management and remains in use, though it has been largely superseded by newer options. Average weight loss of 8-10% is meaningful but substantially lower than Semaglutide or Tirzepatide. Its daily injection schedule is also less convenient than the weekly dosing of newer medications. **Who should still consider it:** Patients who prefer daily rather than weekly dosing (a small minority), those who respond poorly to newer agents, or situations where cost and insurance coverage strongly favor Saxenda. ## Side Effect Comparison: What the Trials Report All GLP-1 medications share a similar side effect profile centered on gastrointestinal symptoms. Nausea is the most common, affecting 40-50% of patients in the first month before typically improving. Our [side effects management guide](/guides/semaglutide-side-effects-how-to-manage) covers practical strategies. Constipation, diarrhea, and occasional vomiting round out the GI picture. | Side Effect | Semaglutide | Tirzepatide | Retatrutide | |-------------|-------------|-------------|-------------| | Nausea | Moderate (44%) | Moderate (42%) | Moderate-High (48%) | | Constipation | Common (24%) | Common (23%) | Common (26%) | | Diarrhea | Moderate (30%) | Moderate (27%) | Moderate (28%) | | Fatigue | Low (11%) | Low (10%) | Moderate (15%) | | Injection site | Low (3.2%) | Low (2.8%) | Low (3.5%) | Proper titration -- starting at the lowest dose and increasing gradually -- is the single most effective strategy for minimizing side effects across all medications. Our [semaglutide dosing schedule](/guides/semaglutide-dosing-schedule-week-by-week-guide) provides a week-by-week plan. ## Cost Comparison (March 2026 Estimates) | Medication | Brand Monthly | Compounded Monthly | |------------|--------------|-------------------| | Semaglutide | $900-1,300 | $200-400 | | Tirzepatide | $1,000-1,200 | $250-500 | | Retatrutide | N/A | $300-600 | | Liraglutide | $1,300-1,500 | $300-500 | Insurance coverage varies significantly by plan and indication. Semaglutide and Tirzepatide are most commonly covered when prescribed for type 2 diabetes. Weight-loss-specific coverage is expanding but remains inconsistent. ## How to Choose: A Decision Framework **Choose Semaglutide if** you want the most established safety profile, cardiovascular protection matters to you (SELECT trial data), you prefer the most affordable compounded option, or you are new to GLP-1 therapy and want a well-studied starting point. **Choose Tirzepatide if** you want higher efficacy than Semaglutide can deliver, you have type 2 diabetes requiring aggressive glucose control, your budget can accommodate slightly higher costs, and you are comfortable with a medication approved since 2022. **Choose Retatrutide if** you have tried other GLP-1 medications without reaching your goals, you need the maximum weight loss available, you are willing to use a medication still under clinical investigation, and you have a provider who will closely monitor your response. ## Switching Between Medications Switching is straightforward and commonly done. Complete your current dose, start the new medication at its lowest dose on your next scheduled injection day, and titrate up following the standard schedule. For a detailed walkthrough, see our [switching from semaglutide to tirzepatide guide](/guides/switching-from-semaglutide-to-tirzepatide-complete-guide). Expect a brief overlap of adjustment symptoms as your body adapts to the new agent. Your provider can customize the transition to minimize discomfort. ## What Comes Next in GLP-1 Development The field is evolving rapidly. Oral Tirzepatide formulations are in late-stage trials. Monthly injection options are under development. Combination approaches pairing GLP-1 agonists with amylin analogs show promising early data. And Retatrutide phase 3 results will likely reshape the competitive landscape when published. This comparison reflects our best understanding of the evidence as of March 2026. For a ranked recommendation, see our [best weight loss injection 2026 guide](/guides/best-weight-loss-injection-2026-complete-guide). For dietary support during treatment, read our [GLP-1 diet guide](/guides/what-to-eat-on-glp1-medications-diet-guide). The right medication depends on your individual health profile, goals, and circumstances -- and that is a decision best made with your healthcare provider — [find a clinic near you](/for-clinics). *Last updated: March 2026. This comparison is for educational purposes. All treatment decisions should be made in consultation with a qualified healthcare provider.* --- ## References - [STEP Trials Program: Semaglutide 2.4mg for Obesity](https://www.nejm.org/doi/full/10.1056/NEJMoa2032183). *New England Journal of Medicine*, 2021. - [SURMOUNT-1: Tirzepatide for Treatment of Obesity](https://www.nejm.org/doi/full/10.1056/NEJMoa2206038). *New England Journal of Medicine*, 2022. - [Retatrutide Phase 2 Trial Results in Obesity](https://www.nejm.org/doi/full/10.1056/NEJMoa2301972). *New England Journal of Medicine*, 2023. - [Comparative Efficacy of GLP-1 Receptor Agonists: A Network Meta-Analysis](https://www.thelancet.com/journals/landia/home). *The Lancet Diabetes & Endocrinology*, 2024. - [SELECT Trial: Semaglutide Cardiovascular Outcomes](https://www.nejm.org/doi/full/10.1056/NEJMoa2307563). *New England Journal of Medicine*, 2023.