Semaglutide is approved for cardiovascular indications for the first time. What other potential treatments for obesity “comorbidities” exist?

Semaglutide will be used to reduce the risk of cardiovascular death, heart attack and stroke in adults with cardiovascular disease and who are obese or overweight, but should be used in conjunction with a low-calorie diet and increased exercise activity. On March 8, Novo Nordisk's powerful weight loss therapy Wegovy (semaglutide) injection was approved by the US FDA for its first cardiovascular disease indication, marking another important breakthrough for the drug in the prevention and treatment of obesity "comorbidities".

The FDA said semaglutide will be used to reduce the risk of cardiovascular death, heart attack and stroke in adults with cardiovascular disease and who are obese or overweight, but should be used in conjunction with a low-calorie diet and increased exercise activity. This makes semaglutide the first weight-loss drug approved to assist in preventing major cardiovascular events in adults with cardiovascular disease and who are obese or overweight.

The efficacy and safety of semaglutide for the new indication of cardiovascular disease were confirmed in a Select multi-center, placebo-controlled, double-blind trial, and the research results were announced at the American Heart Association (AHA) Annual Scientific Meeting held in November last year. A randomized controlled analysis of 17,600 subjects showed that semaglutide significantly reduced the risk of major adverse cardiovascular events (including cardiovascular death, heart attack and stroke), with 6.5% of subjects receiving semaglutide experiencing such events compared with 8% of those receiving placebo.

In this regard, Ge Junbo, academician of the Chinese Academy of Sciences and director of the Department of Cardiology at Zhongshan Hospital of Fudan University, told China Business News: "It is expected that the indications of semaglutide will be expanded to the field of cardiovascular treatment. When the Select trial results were announced at the AHA meeting last year, we predicted that the new indication would be approved soon."

Semaglutide is a GLP-1 receptor agonist that stimulates insulin production and inhibits glucagon secretion, reducing appetite and food intake. Semaglutide was initially approved for marketing as a treatment for type 2 diabetes (trade name: Ozempic). In view of its significant effect in weight loss, in June 2021, the FDA approved it for the treatment of patients with general obesity (trade name: Wegovy). It is the first new drug approved by the US FDA since 2014 to control general obesity or overweight.

Novo Nordisk mentioned a series of plans for the development of semaglutide at the 2024 Capital Markets Day held on March 8, and pointed out that 2.4mg semaglutide has shown the potential to treat obesity-related comorbidities in multiple clinical trials.

China Business News reporter reviewed relevant global clinical studies of semaglutide and noticed that in addition to the Select study targeting cardiovascular adverse events, in another STEP phase III clinical trial, semaglutide 2.4 mg could significantly reduce heart failure-related symptoms and physical limitations in patients with heart failure with preserved ejection fraction (HFpEF) and obesity.

In addition to its cardiac benefits, semaglutide has shown efficacy in kidney disease. The latest FLOW study results announced on March 6 show that semaglutide 1.0 mg can reduce the risk of kidney disease-related events in patients with type 2 diabetes and chronic kidney disease (CKD) by 24%. In October last year, Novo Nordisk said it decided to terminate the trial early based on the efficacy data it had obtained.

Novo Nordisk has also initiated clinical studies of semaglutide for Alzheimer's disease (AD) and non-alcoholic steatohepatitis (NASH). In a phase II clinical trial involving 320 NASH patients, semaglutide dose-dependently improved resolution of NASH symptoms. After 72 weeks of treatment, it significantly improved NASH symptom clearance compared with placebo without worsening liver fibrosis. The related phase III trial ESSENCE has also been launched and is expected to recruit 1,200 patients. The trial is expected to be completed in 2029.

For Alzheimer's disease, there are currently two randomized phase 3 trials, EVOKE and EVOKEPlus, currently recruiting patients to verify the efficacy and safety of oral semaglutide in the treatment of patients with early Alzheimer's disease. Each trial is expected to recruit 1,840 patients, and the trial results are expected to be announced in 2025.

In addition, Novo Nordisk's semaglutide-related pipeline also includes the development of higher-dose injectable dosage forms of 7.2 mg, oral dosage forms of 25/50 mg, and CagriSema (a fixed-dose combination of semaglutide and the long-acting amylin analog cagrilintide).

Research results announced by Novo Nordisk show that the new generation weight loss drug CagriSema showed positive weight loss effects in a 20-week phase I trial. Patients lost about 13% of their weight after taking the drug for 12 weeks, which exceeded the 6% weight loss effect of the older version of the drug during the same cycle. Mid-stage trials of the drug will begin in the second half of this year, with results expected in early 2026.

Novo Nordisk CEO Lars Fruergaard Jorgensen said the company's experimental weight-loss drug CagriSema may eventually become the best treatment for obesity.