FDA Greenlights Wegovy for New Cardiovascular Uses

The FDA's recent approval of Novo Nordisk's Wegovy (semaglutide) for reducing the risk of cardiovascular death, heart attack, and stroke in overweight individuals is a significant development that could pave the way for broader use of GLP-1 agonists. These drugs, initially marketed for type 2 diabetes treatment, have gained attention for their weight loss potential. Wegovy's competitor, tirzepatide (marketed by Eli Lilly as Zepbound), is also undergoing trials for cardiovascular benefits.

Cardiologist Steve Nissen from the Cleveland Clinic suggests that for those with cardiovascular disease and a high BMI, these drugs should be seriously considered, particularly for those at very high risk. Both semaglutide and tirzepatide work by activating GLP-1 receptors, which are triggered by a molecule released after meals to increase insulin secretion and induce a feeling of fullness. Tirzepatide additionally activates receptors for GIP, another post-meal signal.

The potential of GLP-1 agonists to aid in weight loss has been highlighted in various media, including an Oprah Winfrey special. Wegovy was approved for weight loss in 2021, followed by Zepbound in 2023. GlobalData forecasts that GLP-1 agonists will become the most profitable drug class globally, with a market growth rate exceeding 19% per year through 2029.

Novo Nordisk's SELECT trial demonstrated a 20% reduction in major adverse cardiac events (MACE) for overweight or obese patients with cardiovascular disease, even without diabetes. This finding led to the FDA's decision to expand Wegovy's label. However, the role of weight loss in these cardiovascular benefits is debated. Nissen argues that the weight loss is the key factor, dismissing the idea of additional benefits.

Eli Lilly has reported that its drug Trulicity reduced MACE risk in type 2 diabetes patients with cardiovascular risk factors. The company is conducting trials on tirzepatide's cardiovascular effects, with expected data in the coming years.

Both Novo and Lilly are also exploring GLP-1 agonists for heart failure with preserved ejection fraction (HFpEF). Novo has reported improvements with semaglutide in obese patients with HFpEF and is seeking a new indication for this use.

Medicare's coverage policies prohibit the coverage of weight-loss treatments, but classifying Wegovy as a cardiac drug could provide a workaround, allowing coverage for patients with both heart disease and obesity. The Centers for Medicare and Medicaid Services (CMS) have announced coverage for Wegovy to reduce cardiovascular risks in patients with preexisting heart conditions.

The potential expansion of GLP-1 agonist applications extends beyond diabetes, weight loss, and cardiovascular health. Novo recently shared data indicating benefits for cardiovascular and kidney health in patients with type 2 diabetes and chronic kidney disease. Other studies suggest benefits for metabolic dysfunction‐associated steatohepatitis (MASH) and Alzheimer’s disease.

The pharmaceutical industry is witnessing a significant shift as GLP-1 agonists are expected to outpace PD-1 antagonists in sales from 2024, reflecting a demand shift towards addressing metabolic disorders. This development could mark a transformative moment in healthcare, with implications for both patient treatment and pharmaceutical market dynamics.