Tirzepatide versus Semaglutide- Surmount-5 trial reveals head-on comparison results

US: Sharing the topline results from the SURMOUNT-5 phase 3b open-label randomized clinical trial, Eli Lilly and Company announced that participants using its product Zepbound (Tirzepatide) lost 50.3 lbs (22.8 kg) compared to participants on competitor Wegovy (Semaglutide) lost 33.1 lbs (15.0 kg)

Zepbound® (Tirzepatide) provided a 47% greater relative weight loss compared to Wegovy® (Semaglutide), the company stated in its results. On average, Zepbound led to a superior weight loss of 20.2% compared to 13.7% with Wegovy. At 72 weeks, Zepbound beat Wegovy on both the primary endpoint and all five key secondary endpoints in this trial of adults living with obesity or overweight with at least one weight-related medical problem and without diabetes.

"Given the increased interest around obesity medications, we conducted this study to help health care providers and patients make informed decisions about treatment choice," said Leonard C. Glass, MD, FACE, senior vice president of global medical affairs at Lilly Cardiometabolic Health. "We are thrilled that today's findings showed the superior weight loss of Zepbound, which helped patients achieve 47% more relative weight loss compared to Wegovy. Zepbound is in a class of its own as the only FDA-approved dual GIP and GLP-1 receptor agonist obesity medication, changing how millions of people manage this chronic disease."

In addition, in a key secondary endpoint, 31.6% of people taking Zepbound achieved at least 25% body weight loss compared to 16.1% of those taking Wegovy.

The overall safety profile of Zepbound (Tirzepatide) in SURMOUNT-5 was similar to previously reported SURMOUNT trials. The most commonly reported adverse events in SURMOUNT-5 for both Zepbound and Wegovy were gastrointestinal-related and were generally mild to moderate in severity.

What is Surmount Trial?

SURMOUNT-5 (NCT05822830) was a multi-center, randomized, open-label, phase 3b trial evaluating the efficacy and safety of Zepbound® (Tirzepatide) compared with Wegovy® (Semaglutide) in adults with obesity, or overweight with at least one of the following comorbidities: hypertension, dyslipidemia, obstructive sleep apnea (OSA) or cardiovascular disease, who did not have diabetes. The trial randomized 751 participants across the U.S. and Puerto Rico in a 1:1 ratio to receive maximum tolerated dose of Zepbound (10 mg or 15 mg) or Wegovy (1.7 mg or 2.4 mg). The primary objective of the study was to demonstrate Zepbound's superiority in percent change from baseline in body weight at 72 weeks compared to Wegovy. 

Important Information about Tirzepetide - Zepbound/Mounjaro

INDICATION AND SAFETY SUMMARY WITH WARNINGS 

Tirzepatide is a once-weekly dual GIP (glucose-dependent insulinotropic polypeptide) receptor and GLP-1 (glucagon-like peptide-1) receptor agonist. Tirzepatide is a single molecule that activates the body's receptors for GIP and GLP-1, which are natural incretin hormones. Both GIP and GLP-1 receptors are found in areas of the human brain important for appetite regulation. Tirzepatide decreases calorie intake, and the effects are likely mediated by affecting appetite. Studies of Tirzepatide in chronic kidney disease (CKD) and in morbidity/mortality in obesity (MMO) are ongoing. Lilly submitted data for Tirzepatide in moderate-to-severe obstructive sleep apnea (OSA) and obesity and heart failure with preserved ejection fraction (HFpEF) and obesity to the U.S. FDA and other global regulatory agencies earlier this year.

Tirzepatide was approved by the U.S. FDA as Mounjaro® for adults with type 2 diabetes to improve glycemic control on May 13, 2022, and as Zepbound® for adults with obesity or with excess weight and weight-related medical problems on November 8, 2023. Tirzepatide is also commercialized as Mounjaro in some global markets outside the U.S. for adults with obesity or those who are overweight who also have a weight-related comorbid condition. 

Warnings -

Tirzepatide may cause tumors in the thyroid, including thyroid cancer. Watch for possible symptoms, such as a lump or swelling in the neck, hoarseness, trouble swallowing, or shortness of breath. If you have any of these symptoms, tell your healthcare provider. 

Do not use Tirzepatide if you or any of your family have ever had a type of thyroid cancer called medullary thyroid carcinoma (MTC).

Do not use Tirzepatide if you have Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). 

Do not use Tirzepatide if you have had a serious allergic reaction to Tirzepatide or any of the ingredients in Tirzepatide. 

Tirzepatide may cause serious side effects, including: 

Severe stomach problems. Stomach problems, sometimes severe, have been reported in people who use Tirzepatide. Tell your healthcare provider if you have stomach problems that are severe or will not go away. 

Kidney problems (kidney failure). Diarrhea, nausea, and vomiting may cause a loss of fluids (dehydration), which may cause kidney problems. It is important for you to drink fluids to help reduce your chance of dehydration. 

Gallbladder problems. Gallbladder problems have happened in some people who use Tirzepatide. Tell your healthcare provider right away if you get symptoms of gallbladder problems, which may include pain in your upper stomach (abdomen), fever, yellowing of skin or eyes (jaundice), or clay-colored stools. 

Inflammation of the pancreas (pancreatitis). Stop using Tirzepatide and call your healthcare provider right away if you have severe pain in your stomach area (abdomen) that will not go away, with or without vomiting. You may feel the pain from your abdomen to your back. 

Serious allergic reactions. Stop using Tirzepatide and get medical help right away if you have any symptoms of a serious allergic reaction, including swelling of your face, lips, tongue or throat, problems breathing or swallowing, severe rash or itching, fainting or feeling dizzy, or very rapid heartbeat. 

Low blood sugar (hypoglycemia). Your risk for getting low blood sugar may be higher if you use Zepbound with medicines that can cause low blood sugar, such as a sulfonylurea or insulin. Signs and symptoms of low blood sugar may include dizziness or light-headedness, sweating, confusion or drowsiness, headache, blurred vision, slurred speech, shakiness, fast heartbeat, anxiety, irritability, mood changes, hunger, weakness or feeling jittery. 

Changes in vision in patients with type 2 diabetes. Tell your healthcare provider if you have changes in vision during treatment with Zepbound. 

Depression or thoughts of suicide. You should pay attention to changes in your mood, behaviors, feelings or thoughts. Call your healthcare provider right away if you have any mental changes that are new, worse, or worry you. 

Food or liquid getting into the lungs during surgery or other procedures that use anesthesia or deep sleepiness (deep sedation). Tirzepatide may increase the chance of food getting into your lungs during surgery or other procedures. Tell all your healthcare providers that you are taking Tirzepatide before you are scheduled to have surgery or other procedures. 

Common side effects 

The most common side effects of Tirzepatide include nausea, diarrhea, vomiting, constipation, stomach (abdominal) pain, indigestion, injection site reactions, feeling tired, allergic reactions, belching, hair loss, and heartburn. These are not all the possible side effects of Tirzepatide. It is important talk to one's healthcare provider about any side effect that bothers you or doesn't go away.