Comparison

Semaglutide vs Tirzepatide

The two most prescribed GLP-1 weight-loss peptides, compared head to head.

Semaglutide

Established

Brand names: Ozempic, Wegovy, Rybelsus

Long-acting GLP-1 receptor agonist approved for type 2 diabetes and chronic weight management, with established cardiovascular benefit.

Full Semaglutide profile

Tirzepatide

Established

Brand names: Mounjaro, Zepbound

Dual GIP/GLP-1 receptor agonist producing greater average weight loss than semaglutide in head-to-head trials.

Full Tirzepatide profile

Attribute	Semaglutide	Tirzepatide
Category	Incretin / GLP-1 Compounds	Incretin / GLP-1 Compounds
Evidence tier	Established	Established
FDA status	FDA-approved (T2D and chronic weight management). Removed from FDA shortage list in early 2025, limiting compounded versions.	FDA-approved (T2D and chronic weight management).
Mechanism	Semaglutide is a GLP-1 analog that slows gastric emptying, increases satiety, enhances glucose-dependent insulin secretion, and suppresses glucagon. Its 94% homology with native GLP-1 and albumin binding extend half-life to approximately 7 days, enabling weekly dosing.	Tirzepatide activates both GIP and GLP-1 receptors. The GIP component appears to modulate adipose tissue and improve insulin sensitivity, while GLP-1 action drives appetite suppression and glycemic control. Half-life ~5 days enables weekly dosing.
Key benefits	Significant weight loss (10–17% of body weight in STEP trials) Improved glycemic control in type 2 diabetes Reduced major adverse cardiovascular events (SELECT trial) Appetite and food-noise reduction	Up to 22.5% body weight reduction at 15 mg (SURMOUNT-1) Superior HbA1c lowering vs. semaglutide (SURPASS-2) Improvements in sleep apnea severity (SURMOUNT-OSA) Favorable lipid profile changes
Dosage range	0.25 – 2.4 mg weekly	2.5 – 15 mg weekly
Frequency	Weekly	Weekly
Route	SubQ	SubQ
Common side effects	Nausea (most common, dose-dependent), Constipation or diarrhea, Delayed gastric emptying, Fatigue during titration	Nausea, diarrhea, constipation, Injection site reactions, Hypoglycemia when combined with insulin or sulfonylureas

Educational reference only, not medical advice. Data reflects each compound’s profile page; see individual profiles for references and full safety information.

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