Every GLP-1 Medication Compared (2026 Reference)

Based on clinical trials, retatrutide (a triple GLP-1/GIP/glucagon agonist from Eli Lilly) has shown the highest weight loss at approximately 24.2% in Phase 2 trials at 48 weeks. Among FDA-approved medications, tirzepatide (Mounjaro/Zepbound) leads at 20–22.5% in Phase 3 trials (SURMOUNT program, 72 weeks), followed by semaglutide (Wegovy) at 15–16% (STEP trials). CagriSema (semaglutide + cagrilintide) showed 22.7% in Phase 3 (REDEFINE 1) and may receive FDA approval in 2026.

GLP-1 agonists like semaglutide activate one receptor pathway that controls appetite and blood sugar. Dual agonists add a second pathway — either GIP (as in tirzepatide, for enhanced insulin sensitivity) or glucagon (as in survodutide, for increased energy expenditure and liver fat reduction). Triple agonists like retatrutide activate all three pathways simultaneously, which has produced the greatest weight loss in clinical trials to date.

Yes. Rybelsus (oral semaglutide) is approved for type 2 diabetes, and an oral Wegovy formulation launched in January 2026 for weight management. Orforglipron from Eli Lilly is a new non-peptide oral GLP-1 that doesn't require fasting and has an NDA submitted to the FDA with potential approval in mid-2026. VK2735 from Viking Therapeutics is also being tested in oral form.

Without insurance, brand-name GLP-1 medications list at $997–$1,349/month. Self-pay discount programs have reduced this to approximately $299–499/month. With commercial insurance and manufacturer savings cards, some patients pay as low as $25/month. Medicare Part D now covers several GLP-1s at negotiated prices of approximately $245/month with $50 copays. Generic liraglutide (generic Saxenda), launched in August 2025, is currently the most affordable option.

The most common side effects are gastrointestinal: nausea (20–45% of patients), diarrhea (15–30%), vomiting, and constipation. These are typically mild to moderate and occur most often during the dose-escalation period. They usually improve within the first few weeks of treatment. Serious side effects like pancreatitis and gallbladder events are rare but possible.

As of late 2025, Medicare Part D covers Ozempic, Wegovy, Mounjaro, and Zepbound at negotiated prices of approximately $245/month with ~$50 copay for eligible beneficiaries.

Two major decisions are anticipated: CagriSema (Novo Nordisk's semaglutide + cagrilintide combination, showing 22.7% weight loss) and orforglipron (Eli Lilly's first-in-class oral non-peptide GLP-1). Both could reach the US market by late 2026. Further out, retatrutide (triple agonist) and VK2735 (dual GLP-1/GIP) are in Phase 3 trials with potential approvals in 2027–2028.

In the SURMOUNT-5 head-to-head trial, tirzepatide produced greater weight loss than semaglutide at maximum doses (20.2% vs 13.7% at 72 weeks). Tirzepatide is a dual GLP-1/GIP agonist while semaglutide targets only GLP-1. However, semaglutide has more approved indications (including cardiovascular risk reduction, CKD, and MASH) and more extensive long-term safety data. The choice between them depends on individual clinical factors, insurance coverage, and treatment goals.