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For 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 activity1
SURMOUNT-1
Powerful reductions in body weight1
Zepbound 15 mg provided weight reductions ~7x more powerful than placebo1
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
Graphic 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% for Zepbound 5 mg, -19.5% for Zepbound 10 mg, and -20.9% for Zepbound 15 mg vs -3.1% for placebo.
Treatment and placebo included a reduced-calorie diet and increased physical activity.1
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
The proportions of patients who discontinued treatment in SURMOUNT-1 were 14.3%, 16.4%, and 15.1% for the 5 mg, 10 mg, and 15 mg Zepbound-treated groups, respectively, and 26.4% for the placebo-treated group.1
The proportions of patients who discontinued treatment in SURMOUNT-2 were 9.3% and 13.8% for the 10 mg and 15 mg Zepbound-treated groups, respectively, and 14.9% for the placebo-treated group.1
ANCOVA=analysis of covariance; BMI=body mass index; COVID-19=coronavirus disease 2019; ITT= intent-to-treat.
SURMOUNT-1
Proven efficacy at multiple doses1
91% 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. Treatment and placebo included a reduced-calorie diet and increased physical activity.
Treatment and placebo included a reduced-calorie diet and increased physical activity.1
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
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
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
The proportions of patients who discontinued treatment in SURMOUNT-1 were 14.3%, 16.4%, and 15.1% for the 5 mg, 10 mg, and 15 mg Zepbound-treated groups, respectively, and 26.4% for the placebo-treated group.1
The proportions of patients who discontinued treatment in SURMOUNT-2 were 9.3% and 13.8% for the 10 mg and 15 mg Zepbound-treated groups, respectively, and 14.9% for the placebo-treated group.1
BMI=body mass index; COVID-19=coronavirus disease 2019; ITT=intent-to-treat.
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.
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.
BMI=body mass index; GI=gastrointestinal; GLP-1=glucagon-like peptide-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.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 patients1 versus 1.3% of placebo-treated patients1.
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 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 adults who reported at least 1 treatment-emergent occurrence of the adverse reaction.1,3,5
All participants in the clinical trials received Zepbound via the single-dose pen.
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 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
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 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
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.
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 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.1-3
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
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-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.1,4,5
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.1,5
STUDY DESIGN1,5
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.
- 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.