Peptides for Weight Loss: Tirzepatide, Semaglutide, and AOD-9604 Compared

Written by Adam Maggio | Medically reviewed by Dr. James Whitfield, DO, FACOI

Tirzepatide (GIP+GLP-1 dual agonist) produces the most weight loss (~22% body weight), followed by Semaglutide (~15%). AOD-9604 is a GH fragment with fat-burning properties but more modest effects. All work best combined with caloric restriction and exercise.

The Peptide Weight Loss Revolution

The past decade has witnessed a revolution in obesity pharmacotherapy, driven largely by the development of incretin-based peptide therapies. For the first time, pharmaceutical interventions are achieving weight loss outcomes that rival bariatric surgery — without the surgical risks.

Tirzepatide (Mounjaro / Zepbound)

Tirzepatide is the newest and most potent weight loss peptide currently available. It is a dual agonist of both GLP-1 and GIP receptors. The SURMOUNT-1 trial demonstrated average weight loss of 22.5% of body weight at the highest dose (15 mg weekly) over 72 weeks. It is administered via once-weekly subcutaneous injection, with a dose escalation schedule starting at 2.5 mg and titrating up to 15 mg.

Semaglutide (Ozempic / Wegovy)

Semaglutide is a GLP-1 receptor agonist that preceded tirzepatide and remains widely used. The STEP-1 trial demonstrated average weight loss of 14.9% of body weight over 68 weeks at the 2.4 mg weekly dose. While less potent than tirzepatide, semaglutide has a longer track record and more extensive safety data.

AOD-9604

AOD-9604 is a modified fragment of human growth hormone that retains the lipolytic (fat-burning) properties of GH without the anabolic or diabetogenic effects. It stimulates fat breakdown and inhibits lipogenesis through a mechanism independent of the IGF-1 pathway. It has an excellent safety profile and does not cause the nausea and GI side effects associated with GLP-1 agonists. Typical dosing: 300 mcg subcutaneously once daily, ideally in the morning in a fasted state.

Choosing the Right Protocol

For patients with significant obesity who need substantial weight loss, tirzepatide or semaglutide are the evidence-based first choices. AOD-9604 may be appropriate for individuals seeking modest fat loss without the GI side effects of GLP-1 agonists. All peptide weight loss therapies work best when combined with a caloric deficit and regular physical activity.