Semaglutide Demonstrates 20% Reduction in Major Adverse Cardiovascular Events Independent of Weight Loss, Phase III SELECT Trial Results Show

Nov 12, 2023 12:45 CST Updated 12:45

Novo Nordisk

Insulin Developer and Manufacturer

On November 11, 2023, Novo Nordisk announced the latest data from the phase III clinical trial SELECT on the cardiovascular benefits of semaglutide at a 2.4mg dose at the American Heart Association (AHA) Scientific Sessions, which was simultaneously published in the New England Journal of Medicine (NEJM).

Select TestA total of 17,604 subjects were enrolled., suffering from cardiovascular disease and overweight or obesity, but not diabetes.Among them, 8,803 participants received semaglutide (2.4 mg) treatment, and 8,801 participants received placebo treatment. The mean (±SD) duration of semaglutide or placebo treatment was 34.2 ± 13.7 months, with a mean follow-up time of 39.8 ± 9.4 months.

Semaglutide Group8,803 patients569 cases (6.5%)AndPlacebo Group8,801 patients701 cases (8.0%)A major cardiovascular endpoint event occurred (HR: 0.80, p<0.05).

Previously published results show that, compared with placebo,2.4mg of semaglutide can significantly reduce the risk of major adverse cardiovascular events (MACE) by 20% over a period of up to five years.（HR：0.80；95%Cl：0.72；0.90，p<0.001）。

Adverse events leading to permanent discontinuation of the trial drug occurred in 1,461 patients (16.6%) in the semaglutide group and 718 patients (8.2%) in the placebo group (P<0.001).

Today's research results show that,The reduction in major adverse cardiovascular events (MACE) risk is independent of age, gender, race, and baseline body mass index (BMI).

The results also showed that, in terms of MACE risk reduction,The benefits of Semaglutide become apparent shortly after the start of treatment., which suggests that if the 2.4 mg dose of semaglutide fully mediates the cardiovascular effects through weight loss, the resulting effect occurs faster than expected.

Image Source:Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes

In other words, the cardiovascular benefits of semaglutide are likely not solely due to patients' weight loss.

Analysis of the three components of MACE showed that, compared with placebo,The risk of non-fatal myocardial infarction or heart attack was reduced by 28%. (HR: 0.72;95%CI:0.61;0.85)，15% reduction in cardiovascular mortality risk(HR: 0.85; 95% CI: 0.71; 1.01, no statistical significance during the trial period),The risk of non-fatal stroke was reduced by 7% compared to placebo.(HR: 0.93; 95% CI: 0.74, 1.15, not statistically significant during the trial period) Additionally, beneficial effects were observed across all measured cardiovascular endpoints.

The confirmatory secondary endpoint showed that, compared with placebo,The risk of composite heart failure events (including cardiovascular death, emergency visits for heart failure, and hospitalization) was reduced by 18%.(HR:0.82;95%CI:0.71;0.96)，All-cause mortality risk was reduced by 19% compared to placebo.(HR:0.81;95%CI:0.71;0.93) 。

Novo Nordisk announced in a press release that it has applied for updates to the label of Wegovy (the weight-loss version of semaglutide) in the United States and the European Union, expanding its...Reduce the Risk of MACE in Adult Patients with Obesity and Established Cardiovascular Disease"Indications." Currently, the FDA has granted Wegovy priority review status.

The SELECT study of semaglutide has an enormous enrollment scale and is extremely time-consuming. It is no exaggeration to say that Novo Nordisk's financial investment in this trial exceeds the market value of most Biotech companies in China.

This also means that other GLP-1 competitors are almost impossible to replicate the trial scale and conclusions of Semaglutide, which basically solidifies the unshakable position of Semaglutide in terms of cardiovascular benefits among GLP-1 drugs. Especially, the data results of this trial are indeed explosive, confirming that Semaglutide can become one of the most powerful adjuvant drugs in cardiology.

As other GLP-1 targeted drugs have already demonstrated weight loss effects surpassing those of semaglutide, and the entire blood sugar reduction and weight loss market has become highly competitive even at the clinical stage, semaglutide is actively expanding into other disease areas, including the cardiovascular field. It is not only a pioneer but also significantly extending its commercial lifespan.

References

Novo Nordisk A/S: Semaglutide 2.4 mg (Wegovy®) cardiovascular outcomes data presented at American Heart Association Scientific Sessions and simultaneously published in New England Journal of Medicine
Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes

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