Xultophy (insulin degludec/liraglutide)

Zepbound is the weight management brand of tirzepatide from Eli Lilly, FDA-approved in November 2023 for chronic weight management in adults with obesity or overweight with at least one weight-related condition. It contains the same dual GIP/GLP-1 receptor agonist as Mounjaro, but at the same dose range and with the explicit indication for weight loss rather than diabetes. The SURMOUNT clinical trial program produced some of the strongest weight loss data ever seen in a pharmaceutical trial. In SURMOUNT-1[1], participants achieved average weight reductions of 16% on the 5 mg dose, 21.4% on 10 mg, and 22.5% on the 15 mg dose at 72 weeks. More than half of patients on the highest dose lost 20% or more of their body weight. In the head-to-head SURMOUNT-5 trial[2], Zepbound demonstrated 20.2% weight loss compared to 13.7% with semaglutide (Wegovy), representing 47% greater relative weight reduction. Zepbound's list price is approximately $1,086 per month. Through Eli Lilly's LillyDirect self-pay program, single-dose vials are available starting at $299 per month for lower doses, with maintenance doses of 7.5-15 mg priced between $499 and $1,049. Insurance coverage for weight loss medications varies widely, with roughly 16% to 43% of employer plans covering GLP-1s for weight loss as of 2025. For insured patients with coverage, copays can be as low as $25.

Mounjaro is a first-in-class dual GIP/GLP-1 receptor agonist developed by Eli Lilly, FDA-approved for type 2 diabetes management. What sets Mounjaro apart from single-agonist GLP-1 medications is its dual mechanism: it activates both the GIP and GLP-1 receptors simultaneously, which appears to produce stronger metabolic effects than targeting GLP-1 alone. This dual action has translated into some of the most impressive clinical trial results in the diabetes and obesity space. In the SURPASS clinical trial program[1], Mounjaro reduced A1C by 1.9% to 2.4% depending on dose, with nearly 90% of participants achieving an A1C below 7%. The weight loss results were equally striking. Participants on the 15 mg dose lost an average of 29 pounds at 36 weeks in the SURPASS trials[1], significantly outperforming both placebo and comparator drugs like insulin degludec. While only approved for type 2 diabetes, Mounjaro is widely prescribed off-label for weight loss. The list price is approximately $1,080 per month. Eli Lilly's savings card can reduce copays to as low as $25 for commercially insured patients using it for diabetes, but the card typically cannot be used for off-label weight loss prescriptions or with Medicare/Medicaid. Without insurance coverage, GoodRx coupons bring the price to around $1,070.

Retatrutide is an investigational triple hormone receptor agonist being developed by Eli Lilly that targets GIP, GLP-1, and glucagon receptors simultaneously, making it the first drug to activate all three pathways at once. This triple mechanism is believed to enhance metabolic effects beyond what dual agonists like tirzepatide can achieve, with the glucagon component adding increased energy expenditure and fat oxidation to the appetite-suppressing and insulin-sensitizing effects of GIP and GLP-1. The clinical data for retatrutide has been remarkable. In the Phase 2 trial published in the New England Journal of Medicine[1], the 12 mg dose produced 24.2% average weight loss at 48 weeks. The first Phase 3 result from TRIUMPH-4[2] was even more striking: participants achieved up to 28.7% average weight loss (approximately 71 pounds) at the highest dose, along with substantial relief from osteoarthritis pain. However, the Phase 3 data also revealed tolerability concerns, with discontinuation rates of 12.2% and 18.2% for the 9 mg and 12 mg doses respectively, compared to 4% on placebo. Retatrutide is not yet FDA-approved. Seven additional Phase 3 trials in the TRIUMPH program are expected to complete in 2026, covering both obesity and type 2 diabetes indications. If results remain positive, Eli Lilly could submit for FDA approval as early as late 2026, with potential availability in 2027-2028. The drug could represent the next major leap in obesity pharmacotherapy if its safety profile proves acceptable across the broader Phase 3 program.

Wegovy is a higher-dose formulation of semaglutide specifically approved by the FDA for chronic weight management in adults with obesity (BMI 30+) or overweight (BMI 27+) with at least one weight-related comorbidity. Manufactured by Novo Nordisk, it uses the same active ingredient as Ozempic but at a maximum dose of 2.4 mg compared to Ozempic's 2 mg, and it carries an explicit weight loss indication. The STEP clinical trial program[1] established Wegovy as one of the most effective non-surgical weight loss treatments available. In STEP 1[1], participants achieved an average weight loss of 14.9% at 68 weeks, with over half losing 15% or more of their body weight. The two-year STEP 5 trial[2] confirmed sustained results, showing 15.2% weight loss maintained at 104 weeks. In head-to-head comparisons, Wegovy demonstrated strong efficacy, though tirzepatide-based Zepbound showed superior results in the SURMOUNT-5 trial[3]. Wegovy is also available as an oral tablet (approved in late 2025), offering patients an alternative to weekly injections. The injectable version carries a list price of approximately $1,350 per month, though Novo Nordisk's partnership with GoodRx has brought introductory pricing to $199 per month for lower doses. Insurance coverage for weight loss medications remains inconsistent, with many plans still excluding anti-obesity drugs.