Wegovy vs Zepbound: Weight Loss, Cost, Devices and Side Effects

Wegovy and Zepbound are both once-weekly injections given under the skin for long-term weight loss, but they are different molecules from different makers: Wegovy is semaglutide, a GLP-1 receptor agonist from Novo Nordisk ^[1][3], and Zepbound is tirzepatide, a GIP and GLP-1 receptor agonist from Eli Lilly ^[2][4]. In the single head-to-head trial, SURMOUNT-5, adults taking Zepbound at their maximum tolerated dose lost an average of 20.2% of body weight (50 lb) over 72 weeks, compared with 13.7% (33 lb) for adults on Wegovy at their maximum tolerated dose ^[11]. That trial was open-label, and Lilly itself describes the data as collected in a “less rigorous” way, so the findings are less certain ^[11].

The clearest differences between the two drugs are in their approved uses, not their shared core job of weight reduction. Wegovy’s label alone covers heart risk reduction in adults with established cardiovascular disease, fatty liver disease (MASH), and weight loss in patients as young as 12 ^[1][3][6]. Zepbound’s label alone covers moderate-to-severe obstructive sleep apnea in adults with obesity ^[2][5]. Device options and self-pay program prices also differ in ways that may matter to your budget and comfort with needles ^[8][9].

What are the two drugs, and who makes them?

Wegovy is semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist made by Novo Nordisk. It received its first FDA approval on June 4, 2021 ^[1][3]. Zepbound is tirzepatide, a dual glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 receptor agonist made by Eli Lilly. It received its first FDA approval on November 8, 2023 ^[2][4]. Tirzepatide was first approved under the brand name Mounjaro on May 13, 2022, for type 2 diabetes ^[4].

Both injections are given once a week under the skin of the abdomen, thigh, or upper arm ^[1][2]. Wegovy comes in strengths from 0.25 mg up to 2.4 mg, plus a higher 7.2 mg dose sold as Wegovy HD ^[1]. Zepbound comes in strengths from 2.5 mg up to 15 mg ^[2]. Both labels state that use alongside any other GLP-1 receptor agonist is not recommended ^[1][2].

What is each drug FDA-approved to treat?

Wegovy injection is approved, along with a reduced-calorie diet and increased physical activity, for weight reduction and maintenance in adults and pediatric patients aged 12 and older with obesity, and in adults with overweight plus at least one weight-related condition ^[1][3]. The adolescent indication for ages 12 and up was added on December 23, 2022 ^[3]. On March 8, 2024, Wegovy was approved to reduce the risk of major cardiovascular events (cardiovascular death, non-fatal heart attack, or non-fatal stroke) in adults with established cardiovascular disease and either obesity or overweight ^[1][3]. On August 15, 2025, it received accelerated approval for noncirrhotic MASH with moderate to advanced liver fibrosis (stages F2 to F3) in adults ^[1][6].

Zepbound is approved, along with diet and activity, for weight reduction and maintenance in adults with obesity, or overweight plus at least one weight-related condition ^[2]. On December 20, 2024, it was approved to treat moderate-to-severe obstructive sleep apnea in adults with obesity ^[2][5]. Lilly’s labeling states it is not known whether Zepbound is safe and effective in children ^[5][11].

Wegovy is also sold as a once-daily oral tablet (1.5, 4, 9, and 25 mg) for cardiovascular risk reduction and weight reduction in adults ^[1][3].

Which drug produced more weight loss in trials?

The only direct comparison in these materials is SURMOUNT-5, a 72-week, randomized, open-label phase 3b trial in adults with obesity or overweight plus a comorbidity (hypertension, dyslipidemia, obstructive sleep apnea, or cardiovascular disease) and no diabetes. Complete results were published in the New England Journal of Medicine on May 11, 2025 ^[4][11]. Participants on Zepbound at their maximum tolerated dose (10 or 15 mg) lost an average of 20.2% of body weight (50 lb), from an average starting weight of 248.4 lb. Participants on Wegovy at their maximum tolerated dose (1.7 or 2.4 mg) lost an average of 13.7% (33 lb), from an average starting weight of 250 lb ^[11]. Lilly notes the data were collected in a less rigorous study, so the findings are less certain ^[11].

The comparator in SURMOUNT-5 was Wegovy at a maximum of 2.4 mg. Wegovy HD, the 7.2 mg dose, was approved later, on March 19, 2026 ^[7][11]. Novo Nordisk has stated that no other weight loss medicine has been studied to show superiority to Wegovy HD, which is a company claim rather than a trial result ^[7].

Each drug also has placebo-controlled trial results, though these come from separate trials with different populations and cannot be lined up as a direct comparison. In SURMOUNT-1, a 72-week study of adults without diabetes, Zepbound produced average weight loss of 15.0% (34 lb) at 5 mg, 19.5% (44 lb) at 10 mg, and 20.9% (48 lb) at 15 mg, versus 3.1% (7 lb) on placebo ^[4][11]. In SURMOUNT-2, in adults with type 2 diabetes, Zepbound produced 15.7% (34.4 lb) at 15 mg and 13.4% (29.8 lb) at 10 mg, versus 3.3% (7.0 lb) on placebo ^[4]. In STEP UP, a 72-week study of 1,407 adults with obesity and no diabetes, Wegovy HD 7.2 mg produced an average weight reduction of 20.7% if all patients stayed on treatment (18.8% regardless of whether they stayed on treatment), versus 17.5% and 15.5% respectively for the 2.4 mg dose, and 2.4% and 3.9% for placebo. About 31.2% of the 7.2 mg group achieved 25% or greater weight loss, versus 15.3% on 2.4 mg and 0% on placebo ^[7].

What about heart disease, fatty liver, and sleep apnea?

For heart disease, only Wegovy carries a cardiovascular outcomes indication: reducing the risk of cardiovascular death, non-fatal heart attack, or non-fatal stroke in adults with established cardiovascular disease and either obesity or overweight ^[1]. The Zepbound label does not carry a cardiovascular outcomes indication ^[2].

For fatty liver, only Wegovy is approved. Its accelerated MASH approval was based on Part 1 of the ESSENCE trial at week 72, in which 63% of people on Wegovy 2.4 mg (n=534) achieved resolution of steatohepatitis without worsening of fibrosis versus 34% on placebo (n=266), and 37% achieved improvement in liver fibrosis without worsening of steatohepatitis versus 22% on placebo; 33% achieved both versus 16% on placebo, according to Novo Nordisk’s announcement ^[6]. ESSENCE randomized 1,197 participants 2:1 over 240 weeks; Part 2, on liver-related clinical events, is ongoing, and continued approval may be contingent on a confirmatory trial ^[1][6].

For sleep apnea, only Zepbound is approved. The approval was based on the SURMOUNT-OSA trials, which randomized 469 participants to Zepbound (10 or 15 mg) or placebo over 52 weeks. According to Lilly’s announcement, adults not on PAP therapy had 25 fewer breathing interruptions per hour on Zepbound versus 5 on placebo, and adults on PAP therapy had 29 fewer versus 6 on placebo. After one year, 42% of adults on Zepbound without PAP and 50% with PAP experienced remission or mild, non-symptomatic OSA, versus 16% and 14% on placebo. Weight loss averaged 18% (45 lb) without PAP and 20% (50 lb) with PAP, versus 2% on placebo ^[5].

How do the dosing schedules compare?

Wegovy starts at 0.25 mg once weekly for weeks 1 through 4, then escalates every 4 weeks: 0.5 mg (weeks 5–8), 1 mg (weeks 9–12), and 1.7 mg (weeks 13–16), reaching the maintenance dose from week 17. The usual maintenance dose is 2.4 mg. If a dose is not tolerated during escalation, the label says to consider delaying escalation for 4 weeks ^[1]. Wegovy HD 7.2 mg is for adults with obesity who have tolerated 2.4 mg for at least 4 weeks and need additional weight reduction ^[7].

Zepbound starts at 2.5 mg once weekly for 4 weeks, a dose used only for initiation and not approved for maintenance. The dose then increases to 5 mg, and may be increased in 2.5 mg increments after at least 4 weeks on the current dose. Maintenance is 5, 10, or 15 mg for weight reduction, and 10 or 15 mg for obstructive sleep apnea, with a maximum of 15 mg. If a maintenance dose is not tolerated, the label says to consider a lower maintenance dosage ^[2].

Missed-dose rules differ. For Wegovy, take the missed dose as soon as possible if the next scheduled dose is more than 2 days away; if it is less than 2 days away, skip the missed dose. If 2 or more consecutive doses are missed, reinitiate dosage escalation at a lower dose ^[1]. For Zepbound, take the missed dose as soon as possible within 4 days (96 hours); if more than 4 days have passed, skip it ^[2].

What devices do they come in?

Wegovy is available as a single-dose pen in strengths from 0.25 to 7.2 mg, and as a single-dose syringe with an integrated needle in strengths from 0.25 to 2.4 mg. It is also available as a FlexTouch single-patient-use pen containing 9.6 mg/3 mL that delivers four 2.4 mg doses; a new needle is used for each injection, and the pen must never be shared between patients, per a label change recorded in June 2026 ^[1].

Zepbound comes in more formats: a single-dose pen with the needle included, a single-dose vial that requires purchase of a needle and syringe, a multi-dose vial, and a single-patient-use KwikPen that delivers four weekly doses and requires purchase of pen needles. The KwikPen must never be shared between patients ^[2][8]. The KwikPen label expansion was announced on February 23, 2026; single-dose vials launched on August 27, 2024, and all doses became available in vials on June 16, 2025 ^[4][11]. The Zepbound single-dose vial is sold exclusively through LillyDirect on a self-pay basis ^[8].

What do they cost without insurance?

These are manufacturer self-pay program prices, not list prices. Through NovoCare Pharmacy, the Wegovy pen is $349 per month for any dose from 0.25 to 2.4 mg, and Wegovy HD is $399 per month, with a month defined as one box of 4 pens. New patients pay $199 per month for the 0.25 and 0.5 mg doses for their first 2 fills, through December 31, 2026 ^[9].

Through LillyDirect, Zepbound self-pay pricing is $299 per month at 2.5 mg, $399 at 5 mg, and $449 for the 7.5 to 15 mg doses when refilled within 45 days. Without a timely refill, the regular prices are $499 for 7.5 mg and $699 for the 10, 12.5, and 15 mg doses. A month is defined as 28 days, either 4 single-dose vials or 1 KwikPen ^[8].

Monthly self-pay program price	Wegovy (NovoCare)	Zepbound (LillyDirect)
Lowest dose	$199 for 0.25/0.5 mg, first 2 fills, new patients [9]	$299 for 2.5 mg [8]
Standard doses	$349 for 0.25–2.4 mg [9]	$399 for 5 mg; $449 for 7.5–15 mg with refill within 45 days [8]
Highest tier	$399 for Wegovy HD 7.2 mg [9]	$499 for 7.5 mg or $699 for 10–15 mg without a 45-day refill [8]

With commercial insurance, both makers offer savings programs: Wegovy costs as little as $25 per month, subject to a maximum savings of $100 per month, and Zepbound’s single-dose pen is as low as $25 per month for up to a 3-month prescription. Government beneficiaries, including Medicare and Medicaid, are excluded from both ^[8][9]. A Zepbound KwikPen self-pay savings card became available at major pharmacies in March 2026, matching LillyDirect prices; the card does not apply to vials or the single-dose pen ^[13].

For Medicare Part D enrollees, CMS will offer the Medicare GLP-1 Bridge, a time-limited demonstration providing access to certain GLP-1 medications for $50 per monthly supply from July 1, 2026 through December 31, 2027 ^[10]. Lilly points eligible Part D patients with a Zepbound KwikPen prescription for weight management to the program ^[8].

What are the side effects and warnings?

The most common side effects (reported in 5% or more of patients) overlap heavily. For Wegovy they include nausea, diarrhea, vomiting, constipation, abdominal pain, dysesthesia, headache, fatigue, dyspepsia, dizziness, abdominal distension, eructation, hypoglycemia in patients with type 2 diabetes, flatulence, gastroenteritis, GERD, and hair loss ^[1]. For Zepbound they include nausea, diarrhea, vomiting, constipation, abdominal pain, dyspepsia, injection site reactions, fatigue, hypersensitivity reactions, eructation, hair loss, and GERD ^[2].

Both drugs carry a boxed warning about thyroid C-cell tumors seen in rodents, and both are contraindicated in people with a personal or family history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia syndrome type 2. Both labels warn of pancreatitis, gallbladder disease, hypoglycemia when combined with insulin or an insulin secretagogue, acute kidney injury from volume depletion, hypersensitivity, diabetic retinopathy complications, and pulmonary aspiration under anesthesia or deep sedation. Both labels added severe gastrointestinal adverse reaction warnings, Wegovy in October 2025 and Zepbound in February 2026 ^[1][2].

One side effect stands out for Wegovy HD: altered skin sensation, including sensitive skin, hyperesthesia, dysesthesia, and paresthesia, was reported by 22% of participants on the 7.2 mg dose in STEP UP, versus 6% on 2.4 mg and 0.3% on placebo ^[7].

On January 13, 2026, the FDA asked the makers of Saxenda, Wegovy, and Zepbound to remove the warning about suicidal ideation and behavior from their labeling. The decision followed a meta-analysis of 91 placebo-controlled GLP-1 receptor agonist trials including 107,910 patients, which found no increased risk. The removal was recorded on the Wegovy label in January 2026 and the Zepbound label in February 2026 ^[12][1][2].

How do you narrow the choice?

Looking only at labeled indications, the factors that separate the two drugs are: heart disease with obesity or overweight and MASH (Wegovy only) ^[1][6]; moderate-to-severe sleep apnea (Zepbound only) ^[2][5]; and age 12 to 17 (Wegovy only) ^[1][3]. On devices, Wegovy’s pen and syringe options include integrated needles, while Zepbound’s vials require buying a needle and syringe; both drugs have multi-dose single-patient pens that require separate pen needles ^[1][8].

On cost, the Zepbound $449 tier depends on refilling within 45 days, while Wegovy’s program prices are flat by dose tier ^[8][9]. Both labels direct prescribers to choose the maintenance dose based on treatment response and tolerability, with Wegovy allowing a 4-week delay in escalation and Zepbound allowing a lower maintenance dose if a dose is not tolerated ^[1][2]. For pregnancy planning, the Wegovy label says to discontinue at least 2 months before a planned pregnancy because of semaglutide’s long half-life, while the Zepbound label says to discontinue when pregnancy is recognized ^[1][2].

Sources

1. Novo Nordisk. Wegovy prescribing information.
2. National Library of Medicine DailyMed. ZEPBOUND (tirzepatide) injection, solution.
3. Drugs.com. Wegovy (semaglutide) FDA Approval History. May 18, 2026.
4. Drugs.com. Zepbound (tirzepatide) FDA Approval History. February 24, 2026.
5. Eli Lilly and Company. FDA approves Zepbound (tirzepatide) as the first and only prescription medicine for moderate-to-severe obstructive sleep apnea in adults with obesity. December 20, 2024.
6. PR Newswire. Wegovy approved by FDA for the treatment of adults with noncirrhotic MASH with moderate to advanced liver fibrosis.
7. PR Newswire. FDA approves Novo Nordisk’s new Wegovy HD injection, delivering the highest weight loss to date for a Wegovy injection. March 19, 2026.
8. Eli Lilly and Company. Zepbound (tirzepatide) | LillyDirect.
9. Novo Nordisk NovoCare. Wegovy price guide.
10. Centers for Medicare & Medicaid Services. Coming Soon: CMS to Provide $50 Monthly Access to GLP-1 Medications for Medicare Beneficiaries. May 6, 2026.
11. Drugs.com. Zepbound (tirzepatide) Now Available in Multi-Dose KwikPen. February 23, 2026.
12. US Food and Drug Administration. FDA Requests Removal of Suicidal Behavior and Ideation Warning from Glucagon-Like Peptide-1 Receptor Agonist (GLP-1 RA) Medications.
13. Eli Lilly and Company. Media Statement: Zepbound (tirzepatide) KwikPen now available at self-pay pricing at major pharmacies nationwide in addition to LillyDirect. March 16, 2026.