Semaglutide Alternatives & Comparison

Adds GIP to the GLP-1 action, and head-to-head trials generally show more average weight loss

Tirzepatide is a "twincretin" that activates both GIP (glucose-dependent insulinotropic polypeptide) and GLP-1 receptors.

In the SURMOUNT-1 trial (N=2,539), tirzepatide at the 15mg dose achieved an average weight loss of 22.5% over 72 weeks — nearly double the results seen with semaglutide.

A daily GLP-1 injection that has been around longer, if track record is what you weigh

Liraglutide is an acylated, 97%-homologous analog of native human GLP-1, modified with a fatty-acid side chain that lets it bind albumin and resist DPP-4 degradation — extending its half-life from minutes to about 13 hours.

In the pivotal SCALE Obesity and Prediabetes trial (Pi-Sunyer et al.

Daily pill, different molecule, and nothing to inject

Orforglipron is a non-peptide small molecule that binds and activates the GLP-1 receptor directly.

ATTAIN-1 (NCT05869903) was a 72-week phase 3 randomized placebo-controlled trial of 3,127 adults with obesity or overweight plus a weight-related comorbidity (no diabetes), conducted across 10 countries.

An oral drug outside the GLP-1 class, which matters if incretin GI effects are the problem

Bupropion stimulates hypothalamic pro-opiomelanocortin (POMC) neurons, which release alpha-MSH to reduce appetite, but POMC neurons also release beta-endorphin, which feeds back onto mu-opioid receptors on the POMC neurons themselves and shuts them off — limiting the appetite-suppressing effect.

Contrave's FDA approval was supported by four pivotal 56-week phase 3 trials in the Contrave Obesity Research (COR) program.