Weight
Reduction
Who is Zepbound for?
Learn who Zepbound is for
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Clinical data
Learn about clinical data for Zepbound
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SURMOUNT-1 Efficacy
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SURMOUNT-1 Pre-Specified Subgroup Analysis
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Cardiometabolic Parameters
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SURMOUNT-4 Efficacy
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SURMOUNT-5 Efficacy
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SURMOUNT-MAINTAIN Efficacy
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Safety
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Study Designs
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Powerful reductions in body weight1
At 15 mg, Zepbound-treated adults achieved an average weight reduction of almost 21% of their body weight vs 3.1% with placebo at 72 weeks, ~7x more powerful than placebo.2
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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.
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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.
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3 bar graphs showing the percentage of adults who had ≥5% (adjusted for type 1 error), ≥10%, and ≥20% (not adjusted for type 1 error) weight loss in the SURMOUNT-1 trial (Zepbound 5 mg vs placebo at 72 weeks). There were 630 and 643 total adults for Zepbound 5 mg and placebo, respectively. The mean baseline weights were 226.8 lb for Zepbound 5 mg and 231.0 lb for placebo. The percentage of adults achieving ≥5% weight loss was 85.1% for Zepbound 5 mg vs 34.5% for placebo. The percentage of adults achieving ≥10% weight loss was 68.5% for Zepbound 5 mg vs 18.8% for placebo. The percentage of adults achieving ≥20% weight loss was 30% for Zepbound 5 mg vs 3.1% for placebo.
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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.
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Bar graph showing the percentage of adults who had ≥25% 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 ≥25% weight loss was 15.3% for Zepbound 5 mg, 32.3% for Zepbound 10 mg, and 36.2% for Zepbound 15 mg vs 1.5% for placebo.
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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). Severe gastrointestinal adverse reactions have also been reported postmarketing with GLP-1 receptor agonists. Zepbound is not recommended in patients with severe gastroparesis.
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Bar graph showing the mean percentage change in body weight from baseline to week 72 in participants aged 65 and older. For participants taking Zepbound 5 mg (n=52; mean baseline weight=220.9 pounds), the mean percentage change was -14.1% (-31.3 pounds). For participants taking Zepbound 10 mg (n=31; mean baseline weight=217.8 pounds), the mean percentage change was -18.0% (-39.0 pounds). For participants taking Zepbound 15 mg (n=35; mean baseline weight=217.4 pounds), the mean percentage change was -20.3% (-44.6 pounds). For participants taking placebo (n=34; mean baseline weight=217.0 pounds), the mean percentage change was -4.8% (-9.0 pounds).
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Acute Kidney Injury Due to Volume Depletion
There have been postmarketing reports of acute kidney injury, in some cases requiring hemodialysis, in patients treated with GLP‑1 receptor agonists, or Zepbound. The majority of the reported events occurred in patients who experienced gastrointestinal adverse reactions leading to dehydration such as nausea, vomiting, or diarrhea. Monitor renal function in patients reporting adverse reactions to Zepbound that could lead to volume depletion, especially during dosage initiation and escalation of Zepbound.
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Image of the secondary endpoints: cardiometabolic measures. Adjusted for type 1 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 1 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.
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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.
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Line graph depicting percentage change in body weight over time from baseline to 88 weeks comparing people who continued taking Zepbound MTD (10 mg or 15 mg) at 36 weeks vs people who stopped taking Zepbound at 36 weeks. There were 670 patients enrolled, and the overall mean baseline weight was 236.6 lbs. At 36 weeks, the average weight change was -20.9%. From week 36 to 88, the average weight change was -5.5% for the patients who continued with Zepbound MTD (n=335) and +14.0% for the patients who switched to placebo at week 36 (n=335). From week 0 to week 88, patients who continued Zepbound treatment experienced a weight change of -25.8%a vs -9.5%a in those who switched to placebo at week 36. Treatment and placebo included a reduced-calorie diet and increased physical activity.
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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 Zepbound. After initiation of Zepbound, observe patients carefully for signs and symptoms of acute pancreatitis, which may include persistent or severe abdominal pain (sometimes radiating to the back), and which may or may not be accompanied by nausea or vomiting. If pancreatitis is suspected, discontinue Zepbound and initiate appropriate management.
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Line graph showing the percentage change in body weight from baseline to week 72 in the SURMOUNT-5 trial (Zepbound MTD [10 or 15 mg] vs Wegovy MTD [1.7 or 2.4 mg]). There were 374 total adults for Zepbound and 376 total adults for Wegovy. The percentage change in body weight at week 72 was -20.2% (-50.3 lbs) for Zepbound vs -13.7% (-33.1 lbs) for Wegovy.
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.
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Line graph showing the efficacy estimand for the primary endpoint of percentage change in body weight from week 0 to week 112. From week 0 to week 60, the open-label weight-loss period, all adults (n=441) received open-label Zepbound maximum tolerated dose (MTD) (10 mg or 15 mg). At week 60 through week 112, the weight maintenance period, adults were randomized to receive Zepbound MTD, have their dose reduced to Zepbound 5 mg, or switch to placebo. The week 112 data are represented by treatment regimen estimand. Adults receiving Zepbound MTD (n=138) experienced a -21.9% (-54.2 lb) reduction in body weight from baseline to week 112. Adults who had their dose reduced to Zepbound 5 mg (n=142) experienced a -16.6% (-41.4 lb) reduction in body weight at week 112. Adults who switched to placebo (n=90) experienced a -9.9% (-24.9 lb) reduction in body weight at week 112. From week 60 to week 84, rescue Zepbound was not allowed. From week 84 to week 112, rescue Zepbound was allowed. The mean baseline weight was 250.9 lb.
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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 concomitantly administered insulin secretagogue).
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Bar graph showing the key secondary endpoint of percentage maintenance of body weight reduction. Participants taking Zepbound MTD (10 mg or 15 mg) (n=116) maintained 96.5% of their body weight reduction from the weight loss period. Participants who reduced their dose to Zepbound 5 mg (n=118) maintained 67.9% of their body weight reduction from the weight loss period. Participants who switched to placebo (n=76) maintained 42.8% of their body weight reduction from the weight loss period.
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Diabetic Retinopathy Complications in Patients with Type 2 Diabetes Mellitus
Rapid improvement in glucose control has been associated with a temporary worsening of diabetic retinopathy. Tirzepatide has not been studied in patients with non-proliferative diabetic retinopathy requiring acute therapy, proliferative diabetic retinopathy, or diabetic macular edema. Patients with a history of diabetic retinopathy should be monitored for progression of diabetic retinopathy.
DISCONTINUATION
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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). Severe gastrointestinal adverse reactions have also been reported postmarketing with GLP-1 receptor agonists. Zepbound is not recommended in patients with severe gastroparesis.
Select 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). Severe gastrointestinal adverse reactions have also been reported postmarketing with GLP-1 receptor agonists. Zepbound is not recommended in patients with severe gastroparesis.
Select 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). Severe gastrointestinal adverse reactions have also been reported postmarketing with GLP-1 receptor agonists. Zepbound is not recommended in patients with severe gastroparesis.
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Pulmonary Aspiration During General Anesthesia or Deep Sedation
Zepbound delays gastric emptying. There have been rare postmarketing reports of pulmonary aspiration in patients receiving GLP-1 receptor agonists undergoing elective surgeries or procedures requiring general anesthesia or deep sedation who had residual gastric contents despite reported adherence to preoperative fasting recommendations. Available data are insufficient to inform recommendations to mitigate the risk of pulmonary aspiration during general anesthesia or deep sedation in patients taking Zepbound, including whether modifying preoperative fasting recommendations or temporarily discontinuing Zepbound could reduce the incidence of retained gastric contents. Instruct patients to inform healthcare providers prior to any planned surgeries or procedures if they are taking Zepbound.
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