Key takeaways
- In the SURMOUNT-5 head-to-head trial, Zepbound produced 20.2% mean weight loss at 72 weeks against 13.7% for Wegovy, with similar gastrointestinal side-effect rates.
- Wegovy has the cardiovascular outcome evidence (SELECT: 20% relative reduction in major adverse cardiovascular events) and the Medicare indication that goes with it; Zepbound has the obstructive sleep apnea indication and its Medicare route.
- Self-pay in 2026: Zepbound vials through LillyDirect are $299 at 2.5 mg, $399 at 5 mg and $449 at 7.5 to 15 mg under Lilly's Self Pay Journey terms; Wegovy pens through NovoCare are $199 for qualifying initial fills, then $349, and the Wegovy pill is $149 to $299 by dose.
- With insurance coverage, either drug is a $25 to $150 copay with the manufacturer's savings card; which one is covered depends on the plan's formulary, and some PBMs prefer Wegovy.
- For most patients without a cardiovascular indication, Zepbound is the more effective choice; Wegovy is the choice for established cardiovascular disease, for patients who prefer a pill, and where the formulary decides.
Two drugs, one class, one head-to-head trial
Zepbound is tirzepatide, a dual GIP and GLP-1 receptor agonist made by Eli Lilly, approved for chronic weight management in November 2023 and for obstructive sleep apnea in December 2024. Wegovy is semaglutide 2.4 mg, a GLP-1 receptor agonist made by Novo Nordisk, approved for weight management in June 2021 and for cardiovascular risk reduction in March 2024, with a daily tablet approved in December 2025. Both are weekly injections at the maintenance dose, both are titrated over months, and both are chronic therapies: stopping either leads to regaining most of the weight within a year (SURMOUNT-4, STEP 4).
For four years the comparison rested on separate trials with different populations. SURMOUNT-5, published in 2025, put them head to head: 751 adults with obesity randomized to tirzepatide (10 or 15 mg) or semaglutide (1.7 or 2.4 mg) for 72 weeks. Tirzepatide produced 20.2% mean weight loss against 13.7% for semaglutide, a difference of 6.5 percentage points; 64.6% of tirzepatide patients lost at least 15% against 40.1%, and 31.6% lost at least 25% against 16.1%. Waist circumference fell about 7 cm more. Gastrointestinal adverse events were similar in rate and severity between the two arms, and discontinuations for adverse events were roughly comparable.
Where Wegovy has evidence Zepbound does not
Cardiovascular outcomes. SELECT randomized 17,604 adults with established cardiovascular disease and obesity or overweight, without diabetes, to semaglutide 2.4 mg or placebo, and found a 20% relative reduction in major adverse cardiovascular events over about 40 months. That trial produced Wegovy's cardiovascular indication, the first for a weight-management drug, and the Medicare Part D coverage route that goes with it. Tirzepatide's cardiovascular outcome trial (SURPASS-CVOT, in diabetes, against dulaglutide) supports safety and suggests benefit, but Zepbound has no cardiovascular indication for weight management as of our last review.
The tablet. Oral Wegovy (semaglutide 25 mg) produced 13.6% mean weight loss at 64 weeks in OASIS 4 and became the first oral GLP-1 for weight management in December 2025. Tirzepatide has no approved oral form; compounded "oral tirzepatide" products have no absorption evidence.
Where Zepbound has evidence Wegovy does not
Obstructive sleep apnea. SURMOUNT-OSA found tirzepatide reduced the apnea-hypopnea index by about 25 to 29 events per hour against placebo in adults with obesity and moderate-to-severe OSA, producing the December 2024 indication and a Medicare route for beneficiaries with the diagnosis.
More weight loss, and more patients at the thresholds that change health. The SURMOUNT-5 differences at 15%, 20% and 25% loss are the clinically meaningful part of the trial: those are the thresholds at which blood pressure, glycemia, joint pain and sleep apnea improve most.
Side effects
The two drugs share the class profile: nausea, diarrhea, vomiting and constipation concentrated in the escalation weeks; the boxed warning for thyroid C-cell tumors (contraindicated with a personal or family history of medullary thyroid carcinoma or MEN 2); warnings for pancreatitis, gallbladder disease, dehydration and acute kidney injury, hypoglycemia with insulin or sulfonylureas, diabetic retinopathy complications, and suicidal ideation monitoring. SURMOUNT-5 found the gastrointestinal rates similar. Injection-site reactions are somewhat more common with tirzepatide. The side-effects timeline covers what to expect week by week.
Cost in 2026
With insurance coverage. Either drug is typically a $25 to $150 monthly copay with the manufacturer's savings card, and the plan's formulary decides which is covered: some pharmacy benefit managers made Wegovy the preferred GLP-1 for weight management in 2025 and removed Zepbound, so the "better" drug may not be the covered one. Prior authorization criteria (BMI, comorbidities, documented lifestyle attempts) apply to both.
Self-pay. Verified August 25, 2026: Zepbound single-dose vials through LillyDirect are $299 at 2.5 mg, $399 at 5 mg and $449 at 7.5 to 15 mg under Lilly's Self Pay Journey terms (refill within the required window; $499 and $699 regular prices otherwise; terms stated through December 31, 2026). Wegovy pens through NovoCare are $199 per month for qualifying new-patient initial fills, then $349; oral Wegovy is $149 at 1.5 mg and at 4 mg through August 31, 2026 ($199 after), and $299 at 9 and 25 mg. Over a year at maintenance doses, Zepbound vials cost about $4,938 on our titration model and Wegovy pens about $4,000; the difference is roughly the difference in weight loss.
Medicare. Part D may cover Wegovy under the cardiovascular indication and Zepbound under the sleep-apnea indication; the November 2025 manufacturer agreements announced an obesity coverage pathway at $245 to the program with a $50 beneficiary copay, scheduled for 2026. The insurance guide has the details.
Compounded alternatives. For cash patients, compounded tirzepatide at verified prices of $125 to $169 per month on plan terms and compounded semaglutide at $88 to $139 cost a fraction of either brand, without FDA approval, a fixed-dose device or the trial evidence for the specific product. The brand-versus-compounded guide sets out the trade.
Which to choose
Choose Zepbound if your goal is maximum weight loss and you do not have established cardiovascular disease: the head-to-head trial is unambiguous, and the sleep-apnea indication adds a coverage route for patients with that diagnosis. Choose Wegovy if you have established cardiovascular disease (SELECT is the only outcome evidence in the class for weight management), if your formulary covers Wegovy and not Zepbound, if you want a tablet, or if you did well on semaglutide before. Choose whichever is covered if you are insured and the copays are similar, because a covered Wegovy beats a self-pay Zepbound for almost everyone. And if you are self-pay and price is decisive, the honest answer is that both brands cost more than most patients can sustain for years, which is why the compounded rankings exist.
Switching between them
Switching from Wegovy to Zepbound after a plateau is common practice and usually produces additional loss; it is done one week after the last semaglutide dose, starting tirzepatide at 2.5 or 5 mg depending on the dose reached and tolerability. Switching the other way is rare. Either switch requires a prescriber and should not overlap the drugs. The plateau article covers when a switch makes sense.
Frequently asked questions
Is Zepbound better than Wegovy for weight loss?
Yes, in the only head-to-head trial: SURMOUNT-5 found 20.2% mean weight loss with Zepbound against 13.7% with Wegovy over 72 weeks, and a larger share of patients reaching 15%, 20% and 25% loss.
Which is cheaper, Zepbound or Wegovy?
Self-pay at maintenance doses, Wegovy's pen at $349 through NovoCare is below Zepbound's $449 vial through LillyDirect; at the starting dose, Wegovy's $199 initial-fill price is also lower than Zepbound's $299. With insurance, either is a copay and the formulary decides.
Which has fewer side effects?
Gastrointestinal rates were similar in SURMOUNT-5. Both carry the same class warnings (thyroid C-cell tumor boxed warning, pancreatitis, gallbladder disease, hypoglycemia with insulin or sulfonylureas).
Does Medicare cover Zepbound or Wegovy?
Part D may cover Wegovy for cardiovascular risk reduction in adults with established cardiovascular disease and obesity, and Zepbound for obstructive sleep apnea with obesity; the November 2025 agreements announced an obesity pathway scheduled to begin in 2026. Confirm with the plan.
Sources
- Aronne LJ et al. Tirzepatide as Compared with Semaglutide for the Treatment of Obesity (SURMOUNT-5). N Engl J Med 2025.
- Lincoff AM et al. Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes (SELECT). N Engl J Med 2023;389:2221-2232.
- Malhotra A et al. Tirzepatide for the Treatment of Obstructive Sleep Apnea and Obesity (SURMOUNT-OSA). N Engl J Med 2024;391:1193-1205.
- Jastreboff AM et al. SURMOUNT-1. N Engl J Med 2022;387:205-216.
- Wilding JPH et al. STEP 1. N Engl J Med 2021;384:989-1002.
- Zepbound (tirzepatide) and Wegovy (semaglutide) prescribing information, 2025.
- Eli Lilly, Zepbound coverage and savings page (Self Pay Journey vial pricing), verified August 25, 2026.
- NovoCare Wegovy pricing pages (injection and oral), verified August 25, 2026.
Citations are to primary sources (peer-reviewed trials, FDA labeling and announcements, and provider pricing pages). See our sources policy and corrections log.