Clinical Data
SURMOUNT-1
Powerful reductions in body weight1
Adults lost an average of 20.9% of their body weight with Zepbound 15 mg vs 3.1% with placebo1
Zepbound should not be used for cosmetic weight loss.
OVERALL PERCENTAGE CHANGE IN BODY WEIGHT FROM BASELINE AT 72 WEEKS1,2
ZEPBOUND 5 mg
(n=630)
From a mean baseline of 226.8 lb
ZEPBOUND 10 mg
(n=636)
From a mean baseline of 233.3 lb
ZEPBOUND 15 mg
(n=630)
From a mean baseline of 232.8 lb
PLACEBO
(n=643)
From a mean baseline of 231.0 lb
Treatment and placebo included a reduced-calorie diet and increased physical activity.1
Table showing the overall percentage change in body weight from baseline in the SURMOUNT-1 trial (Zepbound 5 mg, 10 mg, and 15 mg vs placebo at 72 weeks). There were 630, 636, 630, and 643 total adults for Zepbound 5 mg, 10 mg, 15 mg, and placebo, respectively. The mean baseline weights were 226.8 lb for Zepbound 5 mg, 233.3 lb for Zepbound 10 mg, 232.8 lb for Zepbound 15 mg, and 231.0 lb for placebo. The percentage change in body weight was -15.0% (-33.9 lb) for Zepbound 5 mg, -19.5% (-44.4 lb) for Zepbound 10 mg, and -20.9% (-48.1 lb) for Zepbound 15 mg vs 3.1% (-6.6 lb) for placebo.
P<0.001 for superiority of Zepbound vs placebo, controlled for type I error.1
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, excluding type 2 diabetes.1
The percentage change in body weight by dose (Zepbound 10 mg and 15 mg) was a coprimary endpoint.3
ITT population includes all randomly assigned patients. The missing values were imputed by a hybrid approach using retrieved dropouts from the same treatment group (if missing not due to COVID-19) or using all non-missing data from the same treatment group assuming missing at random (for missing solely due to COVID-19). Least-squares mean from ANCOVA adjusted for baseline value and other stratification factors.1
In a separate weight-reduction study of adults with a BMI of ≥27 kg/m2 and type 2 diabetes, the overall percentage change in body weight from baseline at 72 weeks was -12.8% (10 mg), -14.7% (15 mg), and -3.2% (placebo). Mean baseline weights were 222.4 lb (10 mg), 219.6 lb (15 mg), and 224.2 lb (placebo).1,4
ANCOVA=analysis of covariance; BMI=body mass index; HI=hybrid imputation; ITT=intent-to-treat; MMRM=mixed model for repeated measures.
Select Important Safety Information
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.
SURMOUNT-1
Powerful reductions in body weight (%) sustained through 72 weeks1
PERCENTAGE CHANGE IN BODY WEIGHT OVER TIME FROM BASELINE TO WEEK 721,2,5
Line graph showing the percentage change in body weight over time from baseline to 72 weeks in the SURMOUNT-1 trial (Zepbound 5 mg, 10 mg, and 15 mg vs placebo). There were 630, 636, 630, and 643 total adults given Zepbound 5 mg, 10 mg, 15 mg, and placebo, respectively, at the start of the trial. There were 601, 593, 595, and 593 total adults given Zepbound 5 mg, 10 mg, 15 mg, and placebo, respectively, at 20 weeks. There were 579, 584, 582, and 522 total adults given Zepbound 5 mg, 10 mg, 15 mg, and placebo, respectively, at 48 weeks. There were 566, 569, 571, and 504 total adults given Zepbound 5 mg, 10 mg, 15 mg, and placebo, respectively, at 72 weeks. There were 630, 636, 630, and 643 total adults given Zepbound 5 mg, 10 mg, 15 mg, and placebo, respectively, at 72 weeks with hybrid imputation. The mean baseline weights were 226.8 lb for Zepbound 5 mg, 233.3 lb for Zepbound 10 mg, 232.8 lb for Zepbound 15 mg, and 231.0 lb for placebo. The observed mean percentage change in body weight at 72 weeks post randomization was -15.0% for Zepbound 5 mg, -19.5% for Zepbound 10 mg, and -20.9% for Zepbound 15 mg vs -3.1% for placebo.
P<0.001 for superiority of Zepbound vs placebo, controlled for type I error.1
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, excluding type 2 diabetes.1
The percentage change in body weight by dose (Zepbound 10 mg and 15 mg) was a coprimary endpoint.3
ITT population includes all randomly assigned patients. Data represent observed mean percent changes in body weight from week 0 to 72 and least-squares mean percent change at week 72. ANCOVA was performed for percent weight change from baseline at week 72 with hybrid imputation.1
In a separate weight-reduction study of adults with a BMI of ≥27 kg/m2 and type 2 diabetes, the overall percentage change in body weight from baseline at 72 weeks was -12.8% (10 mg), -14.7% (15 mg), and -3.2% (placebo). Mean baseline weights were 222.4 lb (10 mg), 219.6 lb (15 mg), and 224.2 lb (placebo).1,4
ANCOVA=analysis of covariance; BMI=body mass index; HI=hybrid imputation; ITT=intent-to-treat.
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
Proven efficacy at multiple doses1
of adults taking Zepbound 15 mg achieved clinically meaningful weight loss of ≥5% at 72 weeks1
PERCENTAGE OF ADULTS WHO ACHIEVED ≥5% WEIGHT LOSS AT 72 WEEKS1,2
Bar graph showing the percentage of adults who had ≥5% weight loss in the SURMOUNT-1 trial (Zepbound 5 mg, 10 mg, and 15 mg vs placebo at 72 weeks). There were 630, 636, 630, and 643 total adults for Zepbound 5 mg, 10 mg, 15 mg, and placebo, respectively. The mean baseline weights were 226.8 lb for Zepbound 5 mg, 233.3 lb for Zepbound 10 mg, 232.8 lb for Zepbound 15 mg, and 231.0 lb for placebo. The percentage of adults achieving ≥5% weight loss was 85.1% for Zepbound 5 mg, 88.9% for Zepbound 10 mg, and 90.9% for Zepbound 15 mg vs 34.5% with placebo.
P<0.001 for superiority of Zepbound vs placebo, controlled for type I error.1
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, excluding type 2 diabetes.1
ITT population includes all randomly assigned patients. The missing values were imputed by a hybrid approach using retrieved dropouts from the same treatment group (if missing not due to COVID-19) or using all non-missing data assuming missing at random (for missing solely due to COVID-19). Analyzed using logistic regression adjusted for baseline value and other stratification factors.1
In a separate weight-reduction study of adults with a BMI of ≥27 kg/m2 and type 2 diabetes, the percentage of patients achieving the primary endpoint of body weight reduction ≥5% at 72 weeks was 79.2% (10 mg), 82.8% (15 mg), and 32.5% (placebo). Mean baseline weights were 222.4 lb (10 mg), 219.6 lb (15 mg), and 224.2 lb (placebo).1,4
BMI=body mass index; COVID-19=coronavirus disease 2019; ITT=intent-to-treat.
Select Important Safety Information
Severe Gastrointestinal Disease: Use of Zepbound has been associated with gastrointestinal adverse reactions, sometimes severe. In clinical trials, 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%). Zepbound has not been studied in patients with severe gastrointestinal disease, including severe gastroparesis, and is therefore not recommended in these patients.
SURMOUNT-1
More than half of adults taking Zepbound 10 and 15 mg lost ≥20% of their body weight1
SECONDARY ENDPOINT: PERCENTAGE OF ADULTS WHO ACHIEVED ≥10% AND ≥20% WEIGHT REDUCTION FROM BASELINE TO WEEK 721-3
2 bar graphs showing the percentage of adults who had ≥10% and ≥20% weight loss in the SURMOUNT-1 trial (Zepbound 10 mg and 15 mg vs placebo at 72 weeks). There were 636, 630, and 643 total adults for Zepbound 10 mg, 15 mg, and placebo, respectively. The mean baseline weights were 233.3 lb for Zepbound 10 mg, 232.8 lb for Zepbound 15 mg, and 231.0 lb for placebo. The percentage of adults achieving ≥10% weight loss was 78.1% for Zepbound 10 mg and 83.5% for Zepbound 15 mg vs 18.8% for placebo. The percentage of adults achieving ≥20% weight loss was 50.1% for Zepbound 10 mg and 56.7% for Zepbound 15 mg vs 3.1% for placebo.
P<0.001 for superiority of Zepbound vs placebo, controlled for type I error.1
The percentage of adults who had ≥10% and ≥20% weight loss in the SURMOUNT-1 trial for 5 mg was 68.5%, and 30% respectively. Not controlled for type I error.1
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, excluding type 2 diabetes.1
ITT population includes all randomly assigned patients. The missing values were imputed by a hybrid approach using retrieved dropouts from the same treatment group (if missing not due to COVID-19) or using all non-missing data assuming missing at random (for missing solely due to COVID-19). Analyzed using logistic regression adjusted for baseline value and other stratification factors.1
In a separate weight-reduction study of adults with a BMI of ≥27 kg/m2 and type 2 diabetes, the percentage of participants achieving reductions ≥10% was 60.5% (10 mg), 64.8% (15 mg), and 9.5% (placebo). The percentage of participants achieving reductions ≥20% was 21.5% (10 mg), 30.8% (15 mg), and 1.0% (placebo). Mean baseline weights were 222.4 lb (10 mg), 219.6 lb (15 mg), and 224.2 lb (placebo).1,4
BMI=body mass index; COVID-19=coronavirus disease 2019; ITT=intent-to-treat.
Select 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.
SURMOUNT-1
Improvements in cardiometabolic parameters at 72 weeks3,6
SECONDARY ENDPOINTS:
POOLED ZEPBOUND 5 MG, 10 MG, AND 15 MG FROM BASELINE TO WEEK 721,3,6
Image of the secondary endpoints: cardiometabolic measures. Adjusted for type I error: HDL cholesterol, systolic blood pressure, and triglycerides. HDL cholesterol: 8.0% increase with Zepbound vs a 0.7% reduction with placebo. (Baseline was 47.6 mg/dL with Zepbound vs 46.6 mg/dL with placebo). Systolic blood pressure: 7.2 mm Hg reduction with Zepbound vs a 1.0 mm Hg reduction with placebo. (Baseline was 123.5 mm Hg with Zepbound vs 122.9 mm Hg with placebo). Triglycerides: 24.8% reduction with Zepbound vs a 5.6% reduction with placebo. (Baseline was 127.5 mg/dL with Zepbound vs 130.8 mg/dL with placebo).
Not adjusted for type I error: LDL cholesterol and diastolic blood pressure. LDL cholesterol: 5.8% reduction with Zepbound vs a 1.7% reduction with placebo. (Baseline was 110.1 mg/dL with Zepbound vs 109.4 mg/dL with placebo). Diastolic blood pressure: 4.8 mm Hg reduction with Zepbound vs a 0.8 mm Hg reduction with placebo. (Baseline was 79.5 mm Hg with Zepbound vs 79.6 mm Hg with placebo).
Zepbound is not indicated for hypertension or dyslipidemia.
Changes in HDL cholesterol, systolic blood pressure, and triglycerides for pooled Zepbound were significant at P<0.001 for superiority vs placebo.3
Treatment and placebo included a reduced-calorie diet and increased physical activity.1
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, excluding type 2 diabetes.1
ITT population includes all randomly assigned patients. The missing values were imputed by a hybrid approach using retrieved dropouts from the same treatment group (if missing not due to COVID-19) or using all non-missing data assuming missing at random (for missing solely due to COVID-19). Least-squares mean from ANCOVA adjusted for baseline value and other stratification factors.1
ANCOVA=analysis of covariance; BMI=body mass index; COVID-19=coronavirus disease 2019; HDL=high-density lipoprotein; ITT=intent-to-treat; LDL=low-density lipoprotein.
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=956) |
|---|---|---|---|---|
| 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 most common adverse reactions occurring more frequently with Zepbound than with placebo were GI related1
- The majority of reports of nausea, vomiting, and/or diarrhea occurred during dose escalation and decreased over time1
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
In a trial of patients with type 2 diabetes mellitus and BMI ≥27 kg/m2, hypoglycemia (plasma glucose <54 mg/dL) was reported in 4.2% of Zepbound-treated patients versus 1.3% of placebo-treated patients.1
In a trial of Zepbound in adults with obesity or with 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 patients versus no placebo-treated patients.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.1,3,7
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.
- The majority of patients who discontinued Zepbound due to adverse reactions did so during the first few months of treatment due to gastrointestinal adverse reactions1
AR=adverse reaction; GI=gastrointestinal.
Select 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 clinical trials of Zepbound, 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. If cholecystitis is suspected, gallbladder diagnostic studies and appropriate clinical follow-up are indicated.
Study Designs
SURMOUNT-1
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 I 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.1-3
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.1,3
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.3
STUDY DESIGN1,3
Graphic of the SURMOUNT-1 study design. After a 2-week screening period, participants (n=2539) were randomly assigned in a 1:1:1:1 ratio to receive once-weekly Zepbound (5 mg, 10 mg, or 15 mg) or placebo for 72 weeks (primary endpoint) that included a dose-escalation period of up to 20 weeks.
*Reduced-calorie diet (approximately 500 kcal/day deficit) and increased physical activity counseling (recommended to a minimum of 150 min/week).1
QW=once weekly.
Select 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 Zepbound clinical trials, 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). Zepbound has not been studied in patients with a prior history of pancreatitis. It is unknown if patients with a history of pancreatitis are at higher risk for development of pancreatitis on Zepbound. 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. If the diagnosis of pancreatitis is confirmed, Zepbound should not be restarted.
SURMOUNT-2
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 ≥27 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.1,4,7
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
STUDY DESIGN1,7
Graphic of the SURMOUNT-2 study design. After a 3-week screening period, participants (n=938) were randomly assigned in a 1:1:1 ratio to receive once-weekly Zepbound (10 mg or 15 mg) or placebo for 72 weeks (primary endpoint) that included a dose-escalation period of up to 20 weeks.
*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.
References
- Zepbound. Prescribing Information. Lilly USA, LLC.
- Data on File. Lilly USA, LLC. DOF-ZP-US-0001.
- 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.
- Data on File. Lilly USA, LLC. DOF-ZP-US-0005.
- Data on File. Lilly USA, LLC. DOF-ZP-US-0006.
- Data on File. Lilly USA, LLC. DOF-ZP-US-0004.
- Garvey WT, Frias JP, Jastreboff AM, et al; for the SURMOUNT-2 Investigators. 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.