
Zepbound is the first and only pharmaceutical treatment approved for moderate-to-severe OSA in adults with obesity in combination with a reduced-calorie diet and increased physical activity.1
Clinical Data: Obstructive Sleep Apnea (OSA)
Zepbound is the first and only pharmaceutical treatment approved for moderate-to-severe OSA in adults with obesity in combination with a reduced-calorie diet and increased physical activity.1
Clinical Data: Obstructive Sleep Apnea (OSA)
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.
See SURMOUNT-OSA designSelect 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.
In SURMOUNT-OSA,
Up to half of adults taking Zepbound achieved the criteria for OSA disease resolution1
Disease resolution is defined as AHI <5 or AHI 5-14 without excessive sleepiness measured by ESS ≤101
% OF ADULTS WITH AHI <5 OR AHI 5-14 AND ESS ≤10 AT WEEK 521,2

Study 1—Not on PAP Therapy
Zepbound MTD
(n=114)
Placebo
(n=120)
Study 2—On PAP Therapy
Zepbound MTD
(n=119)
Placebo
(n=114)
Graph displaying data for the percentage of adults who had an AHI of <5 or an AHI of 5-14 with an ESS ≤10 at week 52. In Study 1 of participants not on PAP therapy, 42.2% of adults taking Zepbound MTD (n=114) had an AHI of <5 or an AHI of 5-14 with an ESS ≤10 vs 15.9% with placebo (n=120). In Study 2 of participants on PAP therapy, 50.2% of adults taking Zepbound MTD (n=119) had an AHI of <5 or an AHI of 5-14 with an ESS ≤10 vs 14.3% with placebo (n=114).
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
Studied over 52 weeks 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
Disease resolution is also characterized as remission or mild non-symptomatic OSA.1
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
mITT population included randomly assigned participants who are exposed to at least 1 dose of study intervention; two participants in Study 2 were randomized but did not receive study drug.1
AHI=apnea-hypopnea index; BMI=body mass index; ESS=Epworth Sleepiness Scale; mITT=modified intent-to-treat; MTD=maximum tolerated dose; OSA=obstructive sleep apnea; PAP=positive airway pressure; PSG=polysomnography.
See SURMOUNT-OSA designSelect 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.
In SURMOUNT-OSA,
Adults taking Zepbound experienced significant reductions in hypoxic burden1a
CHANGE IN SLEEP APNEA-SPECIFIC HYPOXIC BURDEN FROM BASELINE TO WEEK 521,2,a
Study 1—Not on PAP Therapy
Zepbound MTD
(n=114)
From a mean baseline of 153.6% min/hr
Placebo
(n=120)
From a mean baseline of 137.8% min/hr
Study 2—On PAP Therapy
Zepbound MTD
(n=119)
From a mean baseline of 132.2% min/hr
Placebo
(n=114)
From a mean baseline of 142.1% min/hr
Treatment and placebo included a reduced-calorie diet and increased physical activity.2
aSASHB is a metric derived from PSG that quantifies the frequency, duration, and depth of oxygen desaturation associated with respiratory events.2
bP<0.001 for superiority of Zepbound vs placebo, controlled for type I error.1
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
mITT population includes randomly assigned participants who were exposed to at least 1 dose of study intervention. Data represent change in sleep apnea-specific hypoxic burden from week 0 to 52. Least-squares mean from ANCOVA adjusted for baseline values and other stratification factors, with multiple imputation by treatment for missing data at week 52.1
ANCOVA=analysis of covariance; BMI=body mass index; mITT=modified intent-to-treat; MTD=maximum tolerated dose; OSA=obstructive sleep apnea; PAP=positive airway pressure; PSG=polysomnography; SASHB=sleep apnea-specific hypoxic burden.
See SURMOUNT-OSA designSelect Important Safety Information
Severe Gastrointestinal Adverse Reactions: 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.
In SURMOUNT-OSA,
Adults taking Zepbound achieved significant reductions in body weight1
SECONDARY ENDPOINT: PERCENTAGE CHANGE IN BODY WEIGHT OVER TIME FROM BASELINE TO WEEK 521,2,6,a
Treatment and placebo included a reduced-calorie diet and increased physical activity.2
aGraph represents EE; numbers indicate TRE.6
bP<0.001 for superiority of Zepbound vs placebo, controlled for type I error.1
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 from ANCOVA adjusted for baseline values and other stratification factors, with multiple imputation by treatment for missing data at Week 52. For percent change in body weight 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 the study drug.2,4,5
ANCOVA=analysis of covariance; BMI=body mass index; EE=efficacy estimand; mITT=modified intent-to-treat; MTD=maximum tolerated dose; OSA=obstructive sleep apnea; PAP=positive airway pressure; PSG=polysomnography; TRE=treatment regimen estimand.
See SURMOUNT-OSA designSelect Important Safety Information
Acute Kidney Injury: Use of Zepbound has been associated with acute kidney injury, which can result from dehydration due to gastrointestinal adverse reactions to Zepbound, including nausea, vomiting, and diarrhea. In patients treated with GLP-1 receptor agonists, there have been postmarketing reports of acute kidney injury and worsening of chronic renal failure, which may sometimes require hemodialysis. Some of these events have been reported in patients without known underlying renal disease. A majority of the reported events occurred in patients who had experienced nausea, vomiting, diarrhea, or dehydration. Monitor renal function in patients reporting adverse reactions to Zepbound that could lead to volume depletion.
In SURMOUNT-OSA Study 1,
Adults taking Zepbound achieved improvements in cardiometabolic parameters1
SECONDARY ENDPOINTS: CHANGES IN CARDIOMETABOLIC PARAMETERS FROM BASELINE1,2,7,8
Study 1—Not on PAP Therapy
Controlled for Type 1 Error
Systolic Blood Pressurea,d,e
Zepbound MTD baseline=128.4 mm Hg
Placebo baseline=130.3 mmHg
-9.5 mm Hg
with Zepbound MTD
-1.8 mm Hg
with placebo
hsCRPb,e
Zepbound MTD baseline=3.5 mg/L
Placebo baseline=3.6 mg/L
-1.4 mg/L
with Zepbound MTD
-0.7 mg/L
with placebo
Not Controlled for Type 1 Error
HDL Cholesterolc,f,g
Zepbound MTD baseline=43.1 mg/dL
Placebo baseline=44.9 mg/dL
+10.6%
with Zepbound MTD
+3.1%
with placebo
Non-HDL Cholesterolc,f,g
Zepbound MTD baseline=146.6 mg/dL
Placebo baseline=141.6 mg/dL
-15.0%
with Zepbound MTD
-2.3%
with placebo
Diastolic Blood Pressurec,d,e
Zepbound MTD baseline=83.7 mmHg
Placebo baseline=84.0 mmHg
-4.9 mmHg
with Zepbound MTD
-2.1 mmHg
with placebo
Triglyceridesc,f,g
Zepbound MTD baseline=150.1 mg/dL
Placebo baseline=151.4 mg/dL
-32.9%
with Zepbound MTD
-1.0%
with placebo
Zepbound is not indicated for hypertension or dyslipidemia.
Image displaying data for cardiometabolic parameters in Study 1 of participants not on PAP therapy. Endpoints controlled for type I error: For systolic blood pressure, adults taking Zepbound MTD achieved a 9.5 mmHg reduction from a mean baseline of 128.4 mmHg vs a 1.8 mmHg reduction from a mean baseline of 130.3 mmHg with placebo.a,d,e For hsCRP, adults taking Zepbound MTD achieved a 1.4 mg/L reduction from a mean baseline of 3.5 mg/L vs a 0.7 reduction from a mean baseline of 3.6 mg/L with placebo.b,e Endpoints not controlled for type I error: For HDL cholesterol, adults taking Zepbound MTD achieved a 10.6% increase from a mean baseline of 43.1 mg/dL vs a 3.1% increase from a mean baseline of 44.9 mg/dL with placebo.c,f,g For Non-HDL cholesterol, adults taking Zepbound MTD achieved a 15.0% reduction from a mean baseline of 146.6 mg/dL vs a 2.3% reduction from a mean baseline of 141.6 mg/dL with placebo.c,f,g For diastolic blood pressure, adults taking Zepbound MTD achieved a 4.9 mmHg reduction from a mean baseline of 83.7 mmHg vs a 2.1 mmHg reduction from a mean baseline of 84.0 mmHg with placebo.c,d,e For triglycerides, adults taking Zepbound MTD achieved a 32.9% reduction from a mean baseline of 150.1 mg/dL vs a 1.0% reduction from a mean baseline of 151.4 mg/dL with placebo.c,f,g Zepbound is not indicated for hypertension or dyslipidemia.
Treatment and placebo included a reduced-calorie diet and increased physical activity.2
Zepbound is not indicated for hypertension or dyslipidemia.
aP<0.001 for superiority of Zepbound vs placebo, controlled for type I error.2
bP<0.05 for superiority of Zepbound vs placebo, controlled for type I error.2
cSecondary endpoint, not adjusted for multiplicity.2,7
dBP was assessed at Week 48 because PAP withdrawal at Week 52 may confound BP
assessment.2,7,8
eLeast-squares mean from ANCOVA adjusted for baseline values and stratification factors, with
multiple imputation for missing data at Week 52.8
fBaseline value is the geometric mean.8
gLeast-squares mean from mixed model for repeated measures adjusted for
baseline value and stratification factors.8
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.2,3
Randomly assigned participants who are exposed to at least 1 dose of study intervention; two participants in Study 2 were randomized but did not receive study drug.8
ANCOVA=analysis of covariance;BMI=body mass index; HDL=high-density lipoprotein; hsCRP=high-sensitivity C-reactive protein; mITT=modified intent-to-treat; MTD=maximum tolerated dose; OSA=obstructive sleep apnea; PAP=positive airway pressure.
See SURMOUNT-OSA designSelect Important Safety Information
Acute Gallbladder Disease: Treatment with Zepbound and GLP-1 receptor agonists is associated with an increased occurrence of acute gallbladder disease. In a pool of two clinical trials of Zepbound (SURMOUNT-1 and SURMOUNT-2), cholelithiasis was reported in 1.1% of Zepbound-treated patients and 1.0% of placebo-treated patients, cholecystitis was reported in 0.7% of Zepbound-treated patients and 0.2% of placebo-treated patients, and cholecystectomy was reported in 0.2% of Zepbound-treated patients and no placebo-treated patients. Acute gallbladder events were associated with weight reduction. Similar rates of cholelithiasis were reported in Zepbound clinical trials for weight reduction and in Zepbound trials for OSA. If cholecystitis is suspected, gallbladder diagnostic studies and appropriate clinical follow-up are indicated.
In SURMOUNT-OSA Study 2,
Adults taking Zepbound achieved improvements in cardiometabolic parameters1
SECONDARY ENDPOINTS: CHANGES IN CARDIOMETABOLIC PARAMETERS FROM BASELINE1,2,7,8
Study 2—On PAP Therapy
Controlled for Type 1 Error
Systolic Blood Pressurea,c,d
Zepbound MTD baseline=130.5 mm Hg
Placebo baseline=130.5 mm Hg
-7.6 mm Hg
with Zepbound MTD
-3.9 mm Hg
with placebo
hsCRPa,d
Zepbound MTD baseline=3.0 mg/L
Placebo baseline=2.7 mg/L
with Zepbound MTD
-0.3 mg/L
with placebo
Not Controlled for Type 1 Error
HDL Cholesterolb,e,f
Zepbound MTD baseline=42.5 mg/dL
Placebo baseline=45.0 mg/dL
+15.0%
with Zepbound MTD
+4.5%
with placebo
Non-HDL Cholesterolb,e,f
Zepbound MTD baseline=146.6 mg/dL
Placebo baseline=136.3 mg/dL
-15.8%
with Zepbound MTD
-1.8%
with placebo
Diastolic Blood Pressureb,c,d
Zepbound MTD baseline=83.2 mm Hg
Placebo baseline=80.5 mm Hg
-3.3 mm Hg
with Zepbound MTD
-2.2 mm Hg
with placebo
Triglyceridesb,e,f
Zepbound MTD baseline=149.0 mg/dL
Placebo baseline=146.8 mg/dL
-35.2%
with Zepbound MTD
-5.4%
with placebo
Zepbound is not indicated for hypertension or dyslipidemia.
Image displaying data for cardiometabolic parameters in Study 2 of participants on PAP therapy. Endpoints controlled for type I error: For systolic blood pressure, adults taking Zepbound MTD achieved a 7.6 mmHg reduction from a mean baseline of 130.5 mmHg vs a 3.9 mmHg reduction from a mean baseline of 130.5 mmHg with placebo.a,c,d For hsCRP, adults taking Zepbound MTD achieved a 1.4 mg/L reduction from a mean baseline of 3.0 mg/L vs a 0.3 mg/L reduction from a mean baseline of 2.7 mg/L with placebo.a,d Endpoints not controlled for type I error: For HDL cholesterol, adults taking Zepbound MTD achieved a 15.0% increase from a mean baseline of 42.5 mg/dL vs a 4.5% increase from a mean baseline of 45.0 mg/dL with placebo.b,e,f For Non- HDL cholesterol, adults taking Zepbound MTD achieved a 15.8% reduction from a mean baseline of 146.6 mg/dL vs a 1.8% reduction from a mean baseline of 136.3 mg/dL with placebo.b,e,f For diastolic blood pressure, adults taking Zepbound MTD achieved a 3.3 mmHg reduction from a mean baseline of 83.2 mmHg vs a 2.2 mmHg reduction from a mean baseline of 80.5 mmHg with placebo.b,c,d For triglycerides, adults taking Zepbound MTD achieved a 35.2% reduction from a mean baseline of 149.0 mg/dL vs a 5.4% reduction from a mean baseline of 146.8 mg/dL with placebo.b,e,f Zepbound is not indicated for hypertension or dyslipidemia.
Treatment and placebo included a reduced-calorie diet and increased physical activity.2
Zepbound is not indicated for hypertension or dyslipidemia.
aP<0.001 for superiority of Zepbound vs placebo, controlled for type I error.2
bSecondary endpoint, not controlled for type I error.2,7
cBP was assessed at Week 48 because PAP withdrawal at Week 52 may confound BP
assessment.2,7,8
dLeast-squares mean from ANCOVA adjusted for baseline values and stratification factors, with
multiple imputation for missing data at Week 52.8
eBaseline value is the geometric mean.8
fLeast-squares mean from mixed model for repeated measures adjusted for baseline value and
stratification factors.8
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 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.2,3
Randomly assigned participants who are exposed to at least 1 dose of study intervention; two participants in Study 2 were randomized but did not receive study drug.8
ANCOVA=analysis of covariance; BMI=body mass index; HDL=high-density lipoprotein; hsCRP=high-sensitivity C-reactive protein; mITT=modified intent-to-treat; MTD=maximum tolerated dose; OSA=obstructive sleep apnea; PAP=positive airway pressure; PSG=polysomnography.
See SURMOUNT-OSA designSelect Important Safety Information
Acute Pancreatitis: Acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis, has been observed in patients treated with GLP-1 receptor agonists or tirzepatide. In clinical trials of tirzepatide for a different indication, 14 events of acute pancreatitis were confirmed by adjudication in 13 tirzepatide-treated patients (0.23 patients per 100 years of exposure) versus 3 events in 3 comparator-treated patients (0.11 patients per 100 years of exposure). In a pool of two Zepbound clinical trials (SURMOUNT-1 and SURMOUNT-2), 0.2% of Zepbound-treated patients had acute pancreatitis confirmed by adjudication (0.14 patients per 100 years of exposure) versus 0.2% of placebo-treated patients (0.15 patients per 100 years of exposure). The exposure-adjusted incidence rate for treatment-emergent adjudication-confirmed pancreatitis in the pooled clinical studies for OSA was 0.84 patients per 100 years for Zepbound and 0 for placebo-treated patients. Observe patients for signs and symptoms of pancreatitis, including persistent severe abdominal pain sometimes radiating to the back, which may or may not be accompanied by vomiting. If pancreatitis is suspected, discontinue Zepbound and initiate appropriate management. Continuation of Zepbound after a confirmed diagnosis of pancreatitis should be individually determined in the clinical judgment of a patient’s health care provider.
Adverse reactions in SURMOUNT-OSA
Adverse Reactions Occurring in ≥5% of Adults Treated With Zepbound and More Frequently Than Placebo in Either Study1
STUDY 1—NOT ON PAP THERAPY
|
STUDY 2—ON PAP THERAPY
| |||
---|---|---|---|---|
ADVERSE REACTIONS | ZEPBOUND MTD (n=114) | PLACEBO (n=120) | ZEPBOUND MTD (n=119) | PLACEBO (n=114) |
STUDY 1—NOT ON PAP THERAPY | STUDY 2—ON PAP THERAPY | |||
Diarrhea | ZEPBOUND MTD (n=114): 26% | PLACEBO (n=120): 13% | ZEPBOUND MTD (n=119): 22% | PLACEBO (n=114): 9% |
Nausea | ZEPBOUND MTD (n=114): 25% | PLACEBO (n=120): 10% | ZEPBOUND MTD (n=119): 22% | PLACEBO (n=114): 5% |
Vomiting | ZEPBOUND MTD (n=114): 18% | PLACEBO (n=120): 4% | ZEPBOUND MTD (n=119): 9% | PLACEBO (n=114): 1% |
Constipation | ZEPBOUND MTD (n=114): 16% | PLACEBO (n=120): 3% | ZEPBOUND MTD (n=119): 15% | PLACEBO (n=114): 4% |
Eructation | ZEPBOUND MTD (n=114): 8% | PLACEBO (n=120): 0% | ZEPBOUND MTD (n=119): 8% | PLACEBO (n=114): 1% |
Gastroesophageal reflux disease | ZEPBOUND MTD (n=114): 8% | PLACEBO (n=120): 1% | ZEPBOUND MTD (n=119): 5% | PLACEBO (n=114): 0% |
Injection-site reactions | ZEPBOUND MTD (n=114): 7% | PLACEBO (n=120): 1% | ZEPBOUND MTD (n=119): 5% | PLACEBO (n=114): 0% |
Abdominal pain | ZEPBOUND MTD (n=114): 6% | PLACEBO (n=120): 3% | ZEPBOUND MTD (n=119): 4% | PLACEBO (n=114): 2% |
Nasopharyngitis | ZEPBOUND MTD (n=114): 3% | PLACEBO (n=120): 7% | ZEPBOUND MTD (n=119): 13% | PLACEBO (n=114): 11% |
Dyspepsia | ZEPBOUND MTD (n=114): 4% | PLACEBO (n=120): 2% | ZEPBOUND MTD (n=119): 9% | PLACEBO (n=114): 1% |
Gastroenteritis | ZEPBOUND MTD (n=114): 3% | PLACEBO (n=120): 3% | ZEPBOUND MTD (n=119): 7% | PLACEBO (n=114): 1% |
Upper abdominal pain | ZEPBOUND MTD (n=114): 4% | PLACEBO (n=120): 2% | ZEPBOUND MTD (n=119): 6% | PLACEBO (n=114): 2% |
Arrhythmias or cardiac conduction disorders | ZEPBOUND MTD (n=114): 6% | PLACEBO (n=120): 8% | ZEPBOUND MTD (n=119): 5% | PLACEBO (n=114): 2% |
ADVERSE REACTIONS | ZEPBOUND MTD (n=114) | PLACEBO (n=120) | ZEPBOUND MTD (n=119) | PLACEBO (n=114) |
Diarrhea | ZEPBOUND MTD (n=114): 26% | PLACEBO (n=120): 13% | ZEPBOUND MTD (n=119): 22% | PLACEBO (n=114): 9% |
Nausea | ZEPBOUND MTD (n=114): 25% | PLACEBO (n=120): 10% | ZEPBOUND MTD (n=119): 22% | PLACEBO (n=114): 5% |
Vomiting | ZEPBOUND MTD (n=114): 18% | PLACEBO (n=120): 4% | ZEPBOUND MTD (n=119): 9% | PLACEBO (n=114): 1% |
Constipation | ZEPBOUND MTD (n=114): 16% | PLACEBO (n=120): 3% | ZEPBOUND MTD (n=119): 15% | PLACEBO (n=114): 4% |
Eructation | ZEPBOUND MTD (n=114): 8% | PLACEBO (n=120): 0% | ZEPBOUND MTD (n=119): 8% | PLACEBO (n=114): 1% |
Gastroesophageal reflux disease | ZEPBOUND MTD (n=114): 8% | PLACEBO (n=120): 1% | ZEPBOUND MTD (n=119): 5% | PLACEBO (n=114): 0% |
Injection-site reactions | ZEPBOUND MTD (n=114): 7% | PLACEBO (n=120): 1% | ZEPBOUND MTD (n=119): 5% | PLACEBO (n=114): 0% |
Abdominal pain | ZEPBOUND MTD (n=114): 6% | PLACEBO (n=120): 3% | ZEPBOUND MTD (n=119): 4% | PLACEBO (n=114): 2% |
Nasopharyngitis | ZEPBOUND MTD (n=114): 3% | PLACEBO (n=120): 7% | ZEPBOUND MTD (n=119): 13% | PLACEBO (n=114): 11% |
Dyspepsia | ZEPBOUND MTD (n=114): 4% | PLACEBO (n=120): 2% | ZEPBOUND MTD (n=119): 9% | PLACEBO (n=114): 1% |
Gastroenteritis | ZEPBOUND MTD (n=114): 3% | PLACEBO (n=120): 3% | ZEPBOUND MTD (n=119): 7% | PLACEBO (n=114): 1% |
Upper abdominal pain | ZEPBOUND MTD (n=114): 4% | PLACEBO (n=120): 2% | ZEPBOUND MTD (n=119): 6% | PLACEBO (n=114): 2% |
Arrhythmias or cardiac conduction disorders | ZEPBOUND MTD (n=114): 6% | PLACEBO (n=120): 8% | ZEPBOUND MTD (n=119): 5% | PLACEBO (n=114): 2% |
Table displaying adverse reactions occurring in ≥5% of adults treated with Zepbound and more frequently than with placebo in either Study 1 of participants not on PAP therapy treated with Zepbound MTD (n=114) or placebo (n=120) or Study 2 of participants on PAP therapy treated with Zepbound MTD (n=119) or placebo (n=114). In Study 1, diarrhea rates were 26% for Zepbound MTD and 13% for placebo. Nausea rates were 25% for Zepbound MTD and 10% for placebo. Vomiting rates were 18% for Zepbound MTD and 4% for placebo. Constipation rates were 16% for Zepbound MTD and 3% for placebo. Eructation rates were 8% for Zepbound MTD and 0% for placebo. Gastroesophageal reflux disease rates were 8% for Zepbound MTD and 1% for placebo. Injection-site reaction rates were 7% for Zepbound MTD and 1% for placebo. Abdominal pain rates were 6% for Zepbound MTD and 3% for placebo. Nasopharyngitis rates were 3% for Zepbound MTD and 7% for placebo. Dyspepsia rates were 4% for Zepbound MTD and 2% for placebo. Gastroenteritis rates were 3% for Zepbound MTD and 3% for placebo. Upper abdominal pain rates were 4% for Zepbound MTD and 2% for placebo. Rates of arrhythmias or cardiac conduction disorders were 6% for Zepbound MTD and 8% for placebo. In Study 2, diarrhea rates were 22% for Zepbound MTD and 9% for placebo. Nausea rates were 22% for Zepbound MTD and 5% for placebo. Vomiting rates were 9% for Zepbound MTD and 1% for placebo. Constipation rates were 15% for Zepbound MTD and 4% for placebo. Eructation rates were 8% for Zepbound MTD and 1% for placebo. Gastroesophageal reflux disease rates were 5% for Zepbound MTD and 0% for placebo. Injection-site reaction rates were 5% for Zepbound MTD and 0% for placebo. Abdominal pain rates were 4% for Zepbound MTD and 2% for placebo. Nasopharyngitis rates were 13% for Zepbound MTD and 11% for placebo. Dyspepsia rates were 9% for Zepbound MTD and 1% for placebo. Gastroenteritis rates were 7% for Zepbound MTD and 1% for placebo. Upper abdominal pain rates were 6% for Zepbound MTD and 2% for placebo. Rates of arrhythmias or cardiac conduction disorders were 5% for Zepbound MTD and 2% for placebo.
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.1
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
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 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.2
BMI=body mass index; MTD=maximum tolerated dose; OSA=obstructive sleep apnea; PAP=positive airway pressure; PSG=polysomnography.
See SURMOUNT-OSA designSelect Important Safety Information
Hypersensitivity Reactions: There have been postmarketing reports of serious hypersensitivity reactions (e.g., anaphylaxis, angioedema) in patients treated with tirzepatide. In a pool of two Zepbound clinical trials (SURMOUNT-1 and SURMOUNT-2), 0.1% of Zepbound-treated patients had severe hypersensitivity reactions compared to no placebo-treated patients. Similar rates of severe hypersensitivity reactions were observed in Zepbound clinical trials for weight reduction and in Zepbound trials for OSA. If hypersensitivity reactions occur, advise patients to promptly seek medical attention and discontinue use of Zepbound. Do not use in patients with a previous serious hypersensitivity reaction to tirzepatide or any of the excipients in Zepbound. Use caution in patients with a history of angioedema or anaphylaxis with a GLP-1 receptor agonist because it is unknown if such patients will be predisposed to these reactions with Zepbound.
Treatment discontinuation rates from the SURMOUNT- OSA trial1
TREATMENT DISCONTINUATION RATES1
STUDY 1—NOT ON PAP THERAPY
|
STUDY 2—ON PAP THERAPY
| |||
---|---|---|---|---|
TREATMENT DISCONTINUATION | ZEPBOUND MTD (n=114) | PLACEBO (n=120) | ZEPBOUND MTD (n=119) | PLACEBO (n=114) |
STUDY 1—NOT ON PAP THERAPY | STUDY 2—ON PAP THERAPY | |||
Discontinued study treatment | ZEPBOUND MTD (n=114): 14.9% | PLACEBO (n=120): 30.0% | ZEPBOUND MTD (n=119): 10.0% | PLACEBO (n=114): 26.1% |
Table displaying treatment discontinuation rates. In Study 1 of participants not on PAP therapy, 14.9% of people taking Zepbound MTD (n=114) discontinued the study treatment and 30.0% of people taking placebo (n=120) discontinued the study treatment. In Study 2 of participants on PAP therapy, 10.0% of people taking Zepbound MTD (n=119) discontinued the study treatment and 26.1% of people taking placebo (n=114) discontinued the study treatment.
Treatment and placebo included a reduced-calorie diet and increased physical activity.2
OSA=obstructive sleep apnea.
Select Important Safety Information
Hypoglycemia: Zepbound lowers blood glucose and can cause hypoglycemia. In a trial of patients with type 2 diabetes mellitus and BMI ≥27 kg/m2 (Study 2), hypoglycemia (plasma glucose <54 mg/dL) was reported in 4.2% of Zepbound-treated patients versus 1.3% of placebo-treated patients. In this trial, patients taking Zepbound in combination with an insulin secretagogue (e.g., sulfonylurea) had increased risk of hypoglycemia (10.3%) compared to Zepbound-treated patients not taking a sulfonylurea (2.1%). There is also increased risk of hypoglycemia in patients treated with tirzepatide in combination with insulin. Hypoglycemia has also been associated with Zepbound and GLP-1 receptor agonists in adults without type 2 diabetes mellitus. Inform patients of the risk of hypoglycemia and educate them on the signs and symptoms of hypoglycemia. In patients with diabetes mellitus, monitor blood glucose prior to starting Zepbound and during Zepbound treatment. The risk of hypoglycemia may be lowered by a reduction in the dose of insulin or sulfonylurea (or other oncomitantly administered insulin secretagogue).
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.

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Get patients startedReferences
- 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;391(13):1193-1205. 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.
- Data on File. DOF-ZP-US-0027. Lilly USA, LLC.
- Malhotra A, Bednarik J, Chakladar S, et al. Tirzepatide for the treatment of obstructive sleep apnea: Rationale, design, and sample baseline characteristics of the SURMOUNT -OSA phase 3 trial. Contemporary Clinical Trials. 2024;141:107516. doi.org/10.1016/j.cct.2024.107516
- Data on File. DOF-ZP-US-0042. 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.