Survodutide vs retatrutide

Survodutide was characterized in cell assays and mice as a dual glucagon and GLP-1 receptor agonist; in mice it produced larger body-weight reductions than maximally effective semaglutide, which the authors attributed to increased energy expenditure plus reduced food intake (animal data) ⁵. A phase 2 dose-finding trial in 387 adults reported mean body-weight change of up to -14.9% at 46 weeks versus -2.8% with placebo, with gastrointestinal adverse events in 75% versus 42% ⁴.

In the 76-week SYNCHRONIZE-1 trial (725 adults with obesity, no diabetes), mean body-weight change by the treatment-regimen estimand was -12.2% and -13.0% in the two survodutide groups versus -5.4% with placebo ¹. In SYNCHRONIZE-2 (752 adults with type 2 diabetes and obesity), the corresponding values were -8.2% and -9.8% versus -3.9% ². In a 48-week phase 2 biopsy trial in MASH with fibrosis, MASH improvement without worsening of fibrosis occurred in 43-62% of survodutide groups versus 14% with placebo ³.

Retatrutide is a single peptide with agonist activity at the GIP, GLP-1 and glucagon receptors ⁷. In a 48-week phase 2 obesity trial (338 adults), mean body-weight change in the highest-dose group was -24.2% versus -2.1% with placebo, and dose-dependent heart-rate increases peaked at 24 weeks and then declined ⁶.

In the 80-week TRIUMPH-1 phase 3 trial (2,339 adults with obesity without diabetes), mean body-weight change was -17.6%, -23.7% and -25.0% across three dose groups versus -3.9% with placebo ⁸. In TRIUMPH-2 (1,152 adults with obesity and type 2 diabetes), it was -11.9% to -18.8% versus -5.1% at week 80 ⁹. In TRANSCEND-T2D-1 (537 adults with type 2 diabetes), HbA1c changed by -1.69% to -1.94% versus -0.81% with placebo over 40 weeks ¹⁰.