Semaglutide vs. Tirzepatide Guide

Both medications mimic incretin hormones that the gut releases after eating. Semaglutide activates the GLP-1 receptor, which reduces appetite, slows stomach emptying, and improves blood sugar control. Tirzepatide activates the GLP-1 receptor and the GIP receptor. Activating both pathways is thought to contribute to tirzepatide's larger average weight loss.

Read more in our Tirzepatide Guide and our article on how semaglutide works.

SURMOUNT-5, published in the New England Journal of Medicine in 2025, randomly assigned 751 adults with obesity, or overweight with a weight-related condition and without diabetes, to the highest tolerated dose of tirzepatide (10 or 15 mg) or semaglutide (1.7 or 2.4 mg) for 72 weeks.

• Average weight loss was 20.2% with tirzepatide and 13.7% with semaglutide.
• Waist circumference fell by an average of 18.4 cm with tirzepatide and 13.0 cm with semaglutide.
• Most side effects were mild to moderate and occurred during dose increases.

The trial was open-label and funded by Eli Lilly, the maker of tirzepatide. Individual results vary.

• Semaglutide: Ozempic for type 2 diabetes; Wegovy for chronic weight management, cardiovascular risk reduction in adults with heart disease and obesity or overweight, and, under accelerated approval, MASH (a form of fatty liver disease) with liver scarring. A once-daily Wegovy pill was approved for weight management in December 2025.
• Tirzepatide: Mounjaro for type 2 diabetes; Zepbound for chronic weight management and for moderate-to-severe obstructive sleep apnea in adults with obesity.

Both medications share a similar side effect profile. The most common effects are nausea, diarrhea, vomiting, constipation, abdominal discomfort, and reduced appetite, usually when starting or increasing the dose. Both carry a boxed warning about thyroid C-cell tumors seen in rodents and are not used in people with a personal or family history of medullary thyroid carcinoma or MEN 2. Other risks for both include pancreatitis, gallbladder problems, and low blood sugar when combined with insulin or sulfonylureas.

Tirzepatide can reduce the effectiveness of oral birth control pills after starting and after each dose increase. Neither is used during pregnancy.

Tirzepatide produced more weight loss on average in a head-to-head trial, but that doesn't make it the right choice for everyone. Factors your physician considers include:

• Your weight loss and health goals
• Conditions such as heart disease, type 2 diabetes, sleep apnea, or fatty liver disease, where specific approvals may apply
• How you tolerate each medication
• Whether you prefer an injection or a daily pill
• Cost and access

FDA declared the semaglutide and tirzepatide shortages resolved in 2024 and 2025, and the temporary periods that allowed widespread compounded copies have ended. Compounded drugs are not FDA-approved and are not reviewed by FDA for safety, effectiveness, or quality. Ask any provider exactly what product you are receiving and where it is made.