In an interview with Pharmacy Times, Biykem Bozkurt, MD, PhD, professor of medicine and senior dean at Baylor College of Medicine and principal investigator of the SYNCHRONIZE-CVOT (NCT06077864) trial, discussed why survodutide, an investigational glucagon/glucagon-like peptide-1 (GLP-1) receptor dual agonist, required its own cardiovascular outcomes trial.
Bozkurt explained that survodutide represents a new class of incretin-based therapy. GLP-1 receptor activation is associated with improvements in appetite, satiety, glucose control, and weight, while glucagon receptor activation adds complementary metabolic effects, including enhanced lipid metabolism, fatty acid oxidation, and energy expenditure. Because glucagon receptor agonism may have direct effects on the cardiovascular system, she said, its safety had to be tested.
Key Takeaways
- Survodutide adds glucagon receptor agonism to GLP-1 activity, and its potential direct cardiovascular effects meant safety could not be assumed from existing GLP-1 receptor agonist data.
- Sibutramine and fen-phen produced weight loss but carried cardiovascular harms, which is why regulators require cardiovascular safety data for new weight loss classes.
- Bozkurt framed the treatment goal for patients with visceral adiposity as comprehensive cardiometabolic risk reduction, not the amount of weight lost.
Bozkurt pointed to earlier weight loss agents that carried cardiovascular harms: sibutramine was associated with increased blood pressure and cardiovascular events, and fen-phen with valvular abnormalities and pulmonary hypertension. As a result, the FDA and European regulators require cardiovascular safety data for new classes of weight loss agents, much as they do for diabetes medications.
She added that residual cardiovascular risk persists despite the benefits of GLP-1 receptor agonists, because many patients have visceral adiposity linked to cardio-kidney-metabolic and liver disease and die from myocardial infarction, stroke, or cardiovascular death. The target, she said, should be comprehensive cardiometabolic risk modification rather than weight loss alone. Citing earlier SYNCHRONIZE-1, SYNCHRONIZE-2, and liver fat data, Bozkurt said SYNCHRONIZE-CVOT was designed as a noninferiority trial to confirm that the new class is safe in individuals with overweight or obesity who have cardiovascular disease, cardiovascular risk, or chronic kidney disease.
