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NOW APPROVED
Zepbound is the first and only pharmaceutical treatment approved for moderate-to-severe OSA in adults with obesity1
In combination with a reduced-calorie diet and increased physical activity.
NOW APPROVED
Zepbound is the first and only pharmaceutical treatment approved for moderate-to-severe OSA in adults with obesity1
In combination with a reduced-calorie diet and increased physical activity.
INDICATIONS
Zepbound is indicated in combination with a reduced-calorie diet and increased physical activity:
- to reduce excess body weight and maintain weight reduction long term in adults with obesity or adults with overweight in the presence of at least one weight-related comorbid condition.
- to treat moderate-to-severe obstructive sleep apnea (OSA) in adults with obesity.
LIMITATIONS OF USE
Zepbound contains tirzepatide. Coadministration with other tirzepatide-containing products or with any glucagon-like peptide-1 (GLP-1) receptor agonist is not recommended.
Select Important Safety Information
WARNING: RISK OF THYROID C-CELL TUMORS
In rats, tirzepatide causes dose-dependent and treatment-duration-dependent thyroid C-cell tumors at clinically relevant exposures. It is unknown whether Zepbound causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans as human relevance of tirzepatide-induced rodent thyroid C-cell tumors has not been determined.
Zepbound is contraindicated in patients with a personal or family history of MTC or in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). Counsel patients regarding the potential risk for MTC with the use of Zepbound and inform them of symptoms of thyroid tumors (e.g., a mass in the neck, dysphagia, dyspnea, persistent hoarseness). Routine monitoring of serum calcitonin or using thyroid ultrasound is of uncertain value for early detection of MTC in patients treated with Zepbound.
Consider Zepbound for adults with moderate-to-severe OSA and obesity, like Alan*
Not an actual patient.
- He has obesity
- He struggles through fatigue and daytime tiredness
- His recent sleep test reveals an AHI over 15
*Represents an adult patient you may see.
AHI=apnea-hypopnea index; OSA=obstructive sleep apnea.
In SURMOUNT-OSA,
Adults taking Zepbound achieved significant reductions in AHI1
With significant percentage reductions in AHI at week 521
Study 1: 50.7% reduction in AHI from baseline in adults taking Zepbound MTD vs -3.0% with placebo.1
Study 2: 58.7% reduction in AHI from baseline in adults taking Zepbound MTD vs -2.5% with placebo.1
Primary Endpoint: Change in AHI From Baseline to Week 52 (events/h)1,2
Line graph displaying efficacy estimand data points for absolute reduction in AHI at week 0, 20 and 52. In Study 1 of participants not on PAP therapy, adults taking Zepbound MTD (n=114) achieved a reduction of 25.3 events per hour vs 5.3 with placebo (n=120), from mean baselines of 52.9 events per hour and 50.1 events per hour for Zepbound MTD and placebo, respectively. Adults taking Zepbound experienced a 50.7% reduction in AHI vs a 3.0% reduction with placebo from baseline. In Study 2 of participants on PAP therapy, adults taking Zepbound MTD (n=119) achieved a reduction of 29.3 events per hour vs 5.5 with placebo (n=114), from mean baselines of 46.1 events per hour and 53.1 events per hour for Zepbound MTD and placebo, respectively. Adults taking Zepbound experienced a 58.7% reduction in AHI vs a 2.5% reduction with placebo from baseline.
Treatment and placebo included a reduced-calorie diet and increased physical activity.2
aP<0.001 for superiority of Zepbound vs placebo, controlled for type I error.1
bKey secondary endpoint.2
Studied in adults with moderate-to-severe OSA with a BMI ≥30 kg/m2 randomized to receive Zepbound MTD (10 mg or 15 mg) or placebo.2
Study 1 (not on PAP therapy): Participants (n=234) who were unable or unwilling to use PAP therapy. Participants must not have used PAP for at least 4 weeks at the time of screening.1-3
Study 2 (on PAP therapy): Participants (n=235) were on PAP therapy for at least 3 consecutive months at the time of screening and planned to continue PAP therapy during the study. Participants in Study 2 suspended PAP use for 7 days before the scheduled PSGs.1-3
Data shown are least squares mean. Least squares mean at week 52 from ANCOVA adjusted for baseline values and other stratification factors with multiple imputation of missing data are also shown for week 52. For change in AHI from randomization to week 52 data are derived from a mixed-model-for-repeated-measures analysis for the mITT population, and no explicit imputations were performed for missing data. mITT population included randomly assigned participants who are exposed to at least 1 dose of study treatment. Two participants in Study 2 were randomized but did not receive study drug.2,4,5
AHI=apnea-hypopnea index; ANCOVA=analysis of covariance; BMI=body mass index; MI=multiple imputation; mITT=modified intent-to-treat; MTD=maximum tolerated dose; OSA=obstructive sleep apnea; PAP=positive airway pressure; PSG=polysomnography.
Select Important Safety Information
Contraindications: Zepbound is contraindicated in patients with a personal or family history of MTC or in patients with MEN 2, and in patients with known serious hypersensitivity to tirzepatide or any of the excipients in Zepbound. Serious hypersensitivity reactions including anaphylaxis and angioedema have been reported with tirzepatide.
Starting and continuing Zepbound
A once-weekly, subcutaneous injection1
Zepbound Dosing1
Image depicting the dose escalation of Zepbound. Starting dose is 2.5 mg once weekly for 4 weeks. Continue to 5 mg dose once weekly for at least 4 weeks. The dose can be increased to 7.5 mg once weekly for at least 4 weeks, followed by 10 mg maintenance dose once weekly for at least 4 weeks, then 12.5 mg once weekly for at least 4 weeks, and finally 15 mg maintenance dose once weekly as the maximum dose.
Recommended maintenance dosages are 10 mg or 15 mg1:
- Initiate with the 2.5 mg dose
- After 4 weeks, increase to the 5 mg dose
- You can continue to increase the dose by 2.5 mg increments after at least 4 weeks on the current dose. The maximum dose is 15 mg
- Consider treatment response and tolerability when selecting maintenance dosage. If not tolerated, consider a lower maintenance dosage
For adults with moderate-to-severe OSA and obesity in combination with a reduced-calorie diet and increased physical activity.1
The 2.5 mg dosage is for treatment initiation and is not intended to be a maintenance dose.1
AHI=apnea-hypopnea index; BMI=body mass index; OSA=obstructive sleep apnea.
Adverse reactions pooled from the SURMOUNT-1 and SURMOUNT-2 trials1
ADVERSE REACTIONS (≥2% AND GREATER THAN PLACEBO) IN ZEPBOUND-TREATED ADULTS1
ADVERSE REACTIONS
|
ZEPBOUND 5 mg (n=630) |
ZEPBOUND 10 mg (n=948) |
ZEPBOUND 15 mg (n=941) |
PLACEBO (n=958) |
|---|---|---|---|---|
| Nausea | ZEPBOUND 5 mg (n=630): 25% | ZEPBOUND 10 mg (n=948): 29% | ZEPBOUND 15 mg (n=941): 28% | PLACEBO (n=958): 8% |
| Diarrhea | ZEPBOUND 5 mg (n=630): 19% | ZEPBOUND 10 mg (n=948): 21% | ZEPBOUND 15 mg (n=941): 23% | PLACEBO (n=958): 8% |
| Vomiting | ZEPBOUND 5 mg (n=630): 8% | ZEPBOUND 10 mg (n=948): 11% | ZEPBOUND 15 mg (n=941): 13% | PLACEBO (n=958): 2% |
| Constipation | ZEPBOUND 5 mg (n=630): 17% | ZEPBOUND 10 mg (n=948): 14% | ZEPBOUND 15 mg (n=941): 11% | PLACEBO (n=958): 5% |
| Abdominal pain | ZEPBOUND 5 mg (n=630): 9% | ZEPBOUND 10 mg (n=948): 9% | ZEPBOUND 15 mg (n=941): 10% | PLACEBO (n=958): 5% |
| Dyspepsia | ZEPBOUND 5 mg (n=630): 9% | ZEPBOUND 10 mg (n=948): 9% | ZEPBOUND 15 mg (n=941): 10% | PLACEBO (n=958): 4% |
| Injection-site reactions | ZEPBOUND 5 mg (n=630): 6% | ZEPBOUND 10 mg (n=948): 8% | ZEPBOUND 15 mg (n=941): 8% | PLACEBO (n=958): 2% |
| Fatigue | ZEPBOUND 5 mg (n=630): 5% | ZEPBOUND 10 mg (n=948): 6% | ZEPBOUND 15 mg (n=941): 7% | PLACEBO (n=958): 3% |
| Hypersensitivity reactions | ZEPBOUND 5 mg (n=630): 5% | ZEPBOUND 10 mg (n=948): 5% | ZEPBOUND 15 mg (n=941): 5% | PLACEBO (n=958): 3% |
| Eructation | ZEPBOUND 5 mg (n=630): 4% | ZEPBOUND 10 mg (n=948): 5% | ZEPBOUND 15 mg (n=941): 5% | PLACEBO (n=958): 1% |
| Hair Loss | ZEPBOUND 5 mg (n=630): 5% | ZEPBOUND 10 mg (n=948): 4% | ZEPBOUND 15 mg (n=941): 5% | PLACEBO (n=958): 1% |
| Gastroesophageal reflux disease | ZEPBOUND 5 mg (n=630): 4% | ZEPBOUND 10 mg (n=948): 4% | ZEPBOUND 15 mg (n=941): 5% | PLACEBO (n=958): 2% |
| Flatulence | ZEPBOUND 5 mg (n=630): 3% | ZEPBOUND 10 mg (n=948): 3% | ZEPBOUND 15 mg (n=941): 4% | PLACEBO (n=958): 2% |
| Abdominal distension | ZEPBOUND 5 mg (n=630): 3% | ZEPBOUND 10 mg (n=948): 3% | ZEPBOUND 15 mg (n=941): 4% | PLACEBO (n=958): 2% |
| Dizziness | ZEPBOUND 5 mg (n=630): 4% | ZEPBOUND 10 mg (n=948): 5% | ZEPBOUND 15 mg (n=941): 4% | PLACEBO (n=958): 2% |
| Hypotension | ZEPBOUND 5 mg (n=630): 1% | ZEPBOUND 10 mg (n=948): 1% | ZEPBOUND 15 mg (n=941): 2% | PLACEBO (n=958): 0% |
Table of the most common adverse reactions comparing Zepbound vs placebo in the SURMOUNT-1 and SURMOUNT-2 trials. There were 630, 948, 941, and 958 total adults for Zepbound 5 mg, 10 mg, 15 mg, and placebo, respectively. Nausea rates were 25% for Zepbound 5 mg, 29% for Zepbound 10 mg, 28% for Zepbound 15 mg, and 8% for placebo. Diarrhea rates were 19% for Zepbound 5 mg, 21% for Zepbound 10 mg, 23% for Zepbound 15 mg, and 8% for placebo. Vomiting rates were 8% for Zepbound 5 mg, 11% for Zepbound 10 mg, 13% for Zepbound 15 mg, and 2% for placebo. Constipation rates were 17% for Zepbound 5 mg, 14% for Zepbound 10 mg, 11% for Zepbound 15 mg, and 5% for placebo. Abdominal pain rates were 9% for Zepbound 5 mg, 9% for Zepbound 10 mg, 10% for Zepbound 15 mg, and 5% for placebo. Dyspepsia rates were 9% for Zepbound 5 mg, 9% for Zepbound 10 mg, 10% for Zepbound 15 mg, and 4% for placebo. Injection-site reaction rates were 6% for Zepbound 5 mg, 8% for Zepbound 10 mg, 8% for Zepbound 15 mg, and 2% for placebo. Fatigue rates were 5% for Zepbound 5 mg, 6% for Zepbound 10 mg, 7% for Zepbound 15 mg, and 3% for placebo. Hypersensitivity reactions rates were 5% for Zepbound 5 mg, 5% for Zepbound 10 mg, 5% for Zepbound 15 mg, and 3% for placebo. Eructation rates were 4% for Zepbound 5 mg, 5% for Zepbound 10 mg, 5% for Zepbound 15 mg, and 1% for placebo. Hair loss rates were 5% for Zepbound 5 mg, 4% for Zepbound 10 mg, 5% for Zepbound 15 mg, and 1% for placebo. Gastroesophageal reflux disease rates were 4% for Zepbound 5 mg, 4% for Zepbound 10 mg, 5% for Zepbound 15 mg, and 2% for placebo. Flatulence rates were 3% for Zepbound 5 mg, 3% for Zepbound 10 mg, 4% for Zepbound 15 mg, and 2% for placebo. Abdominal distention rates were 3% for Zepbound 5 mg, 3% for Zepbound 10 mg, 4% for Zepbound 15 mg, and 2% for placebo. Dizziness rates were 4% for Zepbound 5 mg, 5% for Zepbound 10 mg, 4% for Zepbound 15 mg, and 2% for placebo. Hypotension rates were 1% for Zepbound 5 mg, 1% for Zepbound 10 mg, 2% for Zepbound 15 mg, and 0% for placebo.
The adverse reactions observed with Zepbound MTD (10 mg or 15 mg) for moderate-to-severe OSA and obesity were consistent with those reported in previous placebo-controlled clinical trials of Zepbound.1,2*
Studied in adults with obesity (BMI of ≥30 kg/m2), or with overweight (BMI of ≥27 kg/m2) with at least 1 weight-related comorbidity, as an adjunct to a reduced-calorie diet and increased physical activity.1
In a trial of adults with type 2 diabetes mellitus and BMI ≥27 kg/m2, hypoglycemia (plasma glucose <54 mg/dL) was reported in 4.2% of Zepbound-treated adults versus 1.3% of placebo-treated adults.1
In a trial of Zepbound in adults with obesity/overweight without type 2 diabetes mellitus, there was no systematic capturing of hypoglycemia, but plasma glucose <54 mg/dL was reported in 0.3% of Zepbound-treated adults versus no placebo-treated adults.1
This table shows common adverse reactions associated with the use of Zepbound in two phase 3 placebo-controlled trials. Percentages reflect the number of adult patients who reported at least 1 treatment-emergent occurrence of the adverse reaction.1,6,7
All participants in the clinical trials received Zepbound via the single-dose pen.
Treatment and placebo included a reduced-calorie diet and increased physical activity.2
*Studied in adults with moderate-to-severe OSA with a BMI ≥30 kg/m2 randomized to receive Zepbound MTD (10 mg or 15 mg) or placebo.2
BMI=body mass index; MTD=maximum tolerated dose; OSA=obstructive sleep apnea.
Treatment discontinuation rates pooled from the SURMOUNT-1 and SURMOUNT-2 trials1
TREATMENT DISCONTINUATION RATES1
TREATMENT DISCONTINUATION
|
ZEPBOUND 5 mg (n=630) |
ZEPBOUND 10 mg (n=948) |
ZEPBOUND 15 mg (n=941) |
PLACEBO (n=958) |
|---|---|---|---|---|
|
Treatment Discontinuation
Due to ARs | ZEPBOUND 5 mg (n=630) 4.8% | ZEPBOUND 10 mg (n=948) 6.3% | ZEPBOUND 15 mg (n=941) 6.7% | PLACEBO (n=958) 3.4% |
|
Treatment Discontinuation
Due to GI ARs | ZEPBOUND 5 mg (n=630) 1.9% | ZEPBOUND 10 mg (n=948) 3.3% | ZEPBOUND 15 mg (n=941) 4.3% | PLACEBO (n=958) 0.5% |
Table of discontinuation rates due to adverse reactions comparing Zepbound vs placebo in the SURMOUNT-1 and SURMOUNT-2 trials. There were 630, 948, 941, and 958 total adults for Zepbound 5 mg, 10 mg, 15 mg, and placebo, respectively. Discontinuation rates due to adverse reactions were 4.8% for Zepbound 5 mg, 6.3% for Zepbound 10 mg, 6.7% for Zepbound 15 mg, and 3.4% for placebo. Discontinuation rates due to gastrointestinal adverse reactions were 1.9% for Zepbound 5 mg, 3.3% for Zepbound 10 mg, 4.3% for Zepbound 15 mg, and 0.5% for placebo.
Studied in adults with obesity (BMI of ≥30 kg/m2) or with overweight (BMI of ≥27 kg/m2), with at least 1 weight-related comorbidity.1
The majority of patients who discontinued Zepbound due to adverse reactions did so during the first few months of treatment due to gastrointestinal adverse reactions. 1
The most common adverse reactions occurring more frequently with Zepbound than with placebo were GI related.1
The majority of reports of nausea, vomiting, and/or diarrhea occurred during dose escalation and decreased over time.1
In Zepbound clinical trials, gastrointestinal adverse reactions occurred more frequently among patients receiving Zepbound (5 mg 56%, 10 mg 56%, 15 mg 56%) than placebo (30%).1
Use of Zepbound has been associated with gastrointestinal adverse reactions, sometimes severe. In a pool of two Zepbound clinical trials (SURMOUNT-1 and SURMOUNT-2), severe gastrointestinal adverse reactions were reported more frequently among patients receiving Zepbound (5 mg 1.7%, 10 mg 2.5%, 15 mg 3.1%) than placebo (1.0%). Similar rates of severe gastrointestinal adverse reactions were observed in Zepbound clinical trials for weight reduction and in Zepbound clinical trials for obstructive sleep apnea (OSA). Zepbound has not been studied in patients with severe gastrointestinal disease, including severe gastroparesis, and is therefore not recommended in these patients.
AR=adverse reaction; GI=gastrointestinal.
Select Important Safety Information
Risk of Thyroid C-cell Tumors: Counsel patients regarding the potential risk for MTC with the use of Zepbound and inform them of symptoms of thyroid tumors (e.g., a mass in the neck, dysphagia, dyspnea, persistent hoarseness). Routine monitoring of serum calcitonin or using thyroid ultrasound is of uncertain value for early detection of MTC in patients treated with Zepbound. Such monitoring may increase the risk of unnecessary procedures, due to the low test specificity for serum calcitonin and a high background incidence of thyroid disease. Significantly elevated serum calcitonin values may indicate MTC and patients with MTC usually have calcitonin values >50 ng/L. If serum calcitonin is measured and found to be elevated, the patient should be further evaluated. Patients with thyroid nodules noted on physical examination or neck imaging should also be further evaluated.
SURMOUNT-1 study design
SURMOUNT-1 was a 72-week, double-blind, placebo-controlled, phase 3 trial that randomized 2539 adult patients with a body mass index (BMI) of ≥30 kg/m2 or ≥27 kg/m2 and at least 1 weight-related comorbid condition (study excluded patients with type 1 diabetes or type 2 diabetes), to receive once-weekly subcutaneous Zepbound 5 mg, 10 mg, 15 mg, or placebo (1:1:1:1 ratio), including a 20-week dose-escalation period. Treatment was an adjunct to a reduced-calorie diet and increased physical activity.* Mean baseline body weight for Zepbound 5 mg was 226.8 lb, for Zepbound 10 mg 233.3 lb, for Zepbound 15 mg 232.8 lb, and for placebo 231.0 lb.1,6,8
Coprimary endpoints were to demonstrate that Zepbound 10 mg and/or 15 mg are superior to placebo for mean percent change in body weight from baseline and percentage of study participants who achieved ≥5% body weight reduction at 72 weeks.1,6
Secondary endpoints were assessed at 72 weeks: superiority of Zepbound 5 mg to placebo for mean percent change in body weight and percentage of participants who achieved ≥5% body weight reduction; superiority of Zepbound 10 mg and/or 15 mg to placebo for percentage of participants who achieved ≥10% body weight reduction, ≥15% body weight reduction, and/or ≥20% body weight reduction.6
SURMOUNT-2 study design
SURMOUNT-2 was a 72-week, double-blind, placebo-controlled, phase 3 trial that randomized 938 adult patients with a body mass index (BMI) of 22.7 kg/m2 and type 2 diabetes to receive once-weekly subcutaneous Zepbound 10 mg, 15 mg, or placebo (1:1:1 ratio), including a 20-week dose-escalation period. Treatment with Zepbound or placebo was an adjunct to a reduced-calorie diet and increased physical activity.* Patients included in the trial were treated with diet and exercise alone or with any oral anti-hyperglycemic agent except DPP-4 inhibitors or GLP-1 receptor agonists. Patients taking injectable therapies for type 2 diabetes were excluded from the study. Mean baseline body weight was 222.4 lb for Zepbound 10 mg, 219.6 lb for Zepbound 15 mg, and 224.2 lb for placebo.1,7,9
Coprimary endpoints were to demonstrate that Zepbound 10 mg and/or 15 mg are superior to placebo for mean percent change in body weight from baseline and percentage of study participants who achieved ≥5% body weight reduction at 72 weeks.1
Some key secondary endpoints assessed at 72 weeks were superiority of Zepbound 10 mg and/or 15 mg to placebo for percentage of participants who achieved ≥10%, ≥15%, and/or ≥20% body weight reduction; mean change in A1C (%); percentage of participants who achieved A1C <7%; and mean change in fasting glucose.1,7
*Reduced-calorie diet (approximately 500 kcal/day deficit) and increased
physical
activity counseling (recommended to a minimum of 150 min/week).1
DPP-4=dipeptidyl peptidase-4; GLP-1=glucagon-like peptide-1; QW=once weekly.
SURMOUNT-OSA study design
2 studies evaluating the effect of Zepbound in adults with moderate-to-severe OSA and obesity1,2
The SURMOUNT-OSA program included two 52-week phase 3, randomized, double-blind, placebo-controlled studies to evaluate the efficacy and safety of Zepbound at the maximum tolerated dose (10 mg or 15 mg) vs placebo as an adjunct to a reduced-calorie diet and increased physical activity. Primary endpoint of both studies was the change in the apnea-hypopnea index (AHI) from baseline.1,2
Participants had moderate-to-severe OSA (AHI ≥15 events/h) and obesity (BMI ≥30 kg/m2) without type 1 or type 2 diabetes.1,2
The participant population was composed of ~70% male adults.2
- Study 1 (not on PAP therapy): Participants (n=234) who were unable or unwilling to use PAP therapy. Participants must not have used PAP for at least 4 weeks at the time of screening.1-3
- Study 2 (on PAP therapy): Participants (n=235) were on PAP therapy for at least 3 consecutive months at the time of screening and planned to continue PAP therapy during the study.1-3*
*Participants in Study 2 suspended PAP use for 7 days before the scheduled PSGs and Patient-Reported Outcome (PRO) assessments.2
AHI=apnea-hypopnea index; BMI=body mass index; OSA=obstructive sleep apnea; PAP=positive airway pressure; PSG=polysomnography.
References
- Zepbound. Prescribing Information. Lilly USA, LLC.
- Malhotra A, Grunstein RR, Fietze I, et al. Tirzepatide for the treatment of obstructive sleep apnea and obesity. N Engl J Med. 2024. doi:10.1056/NEJMoa2404881
- Malhotra A, Grunstein RR, Fietze I, et al. Tirzepatide for the treatment of obstructive sleep apnea and obesity. N Engl J Med. 2024; (suppl append). doi:10.1056/NEJMoa2404881
- Data on File. DOF-ZP-US-0028. Lilly USA, LLC.
- Data on File. DOF-ZP-US-0029. Lilly USA, LLC.
- Jastreboff AM, Aronne LJ, Ahmad NN, et al. Tirzepatide once weekly for the treatment of obesity. N Engl J Med. 2022;387(3):205-216. doi:10.1056/NEJMoa2206038
- Garvey WT, Frias JP, Jastreboff AM, et al. Tirzepatide once weekly for the treatment of obesity in people with type 2 diabetes (SURMOUNT-2): a double-blind, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet. 2023;402(10402):613-626. doi:10.1016/S0140-6736(23)01200-X
- Data on File. DOF-ZP-US-0001. Lilly USA, LLC.
- Data On File. DOF-ZP-US-0005. Lilly USA, LLC.