Introduction:

Survodutide is dual glucagon/glucagon-like peptide-1 receptor (GCGR/GLP-1R) agonist and has a single molecule. Currently it is in the phase 3 studies for 2 goals: long-term weight loss in people with obesity and treatment of metabolic dysfunction–associated steatohepatitis (MASH). It was seen that Survodutide elicited up to 18.7% mean reduction in body weight after 46 weeks in a multinational phase 2 clinical trial in individuals with obesity without diabetes. In this double-blind trial changes in molecular markers of adiposity, inflammation, insulin resistance, coagulation, and atherosclerosis were explored.

Methods:

1. 387 adults aged 18–74 years and BMI ≥ 27 kg/m² (with similar baseline demographics), without diabetes were randomized to once-weekly placebo or survodutide for 46 weeks.
2. Survodutide doses were titrated up to 0.6, 2.4, 3.6, or 4.8 mg over ≤20 weeks, with reductions allowed for gastrointestinal tolerability and then held steady.
3. All participants who received ≥1 dose and had ≥1 efficacy measurement were included in the full analysis set; data were grouped by the maintenance dose actually received.
4. Plasma leptin, ICAM-1, E-selectin, apolipoprotein A, C-reactive protein, PEDF, coagulation factor VII, and CCL18 were measured using a Luminex xMAP multiplex assay.
5. On-treatment values were assessed with a mixed model for repeated measures.

Results:

The table compares and shows how plasma biomarker levels changed after 46 weeks of treatment with the highest survodutide dose (4.8 mg once weekly) versus placebo.

ICAM-1 - Intercellular adhesion molecule

PEDF - pigment epithelium-derived factor

CCL18 - CC chemokine ligand 18

Conclusion:

It was concluded that treatment with dual GCGR/GLP-1R agonist survodutide was associated with improvements in molecular markers of cardiometabolic health and cardiovascular risk in people living with obesity.

ECO, 11-14 May 2025, Malaga, Spain