US FDA approves first oral diabetes drug to prevent heart attacks, stroke: Doctors break down how Rybelsus works

Rybelsus, which is being used for diabetes management in India from 2022, was first cleared in 2019. But now the FDA has expanded its use based on new evidence from the SOUL trial, which showed the drug can reduce cardiovascular risks in patients by almost 14 per cent.

What trial results show

The study, which was published in the New England Journal of Medicine, followed 9,650 adults with Type 2 diabetes and a high cardiovascular risk for nearly four years. One group received a daily 14 mg dose of oral semaglutide while the other received a placebo in addition to standard diabetes and heart medication. The risk of a major adverse cardiovascular event (MACE) was reduced by a significant 14 per cent in the drug group. And the benefits were the same across patient subgroups, including those who had not yet experienced a cardiovascular event. The overall safety profile of Rybelsus was consistent with what has been seen in earlier studies.

Serious adverse cardiac events were less frequent among those taking Rybelsus (47.9 per cent) compared to those on placebo (50.3 per cent). However, gastrointestinal side effects, such as nausea and vomitting, was slightly higher with the drug, (5.0 per cent versus 4.4 per cent in the other group).

“Considering that Indians are prone to premature heart attacks and have a huge burden of diabetes, which is the biggest risk factor for heart disease, an oral drug to control both can make a huge difference. It helps to not only reduce HbA1c (average blood sugar count of three months) but also reduce weight,” says Dr V Mohan, chairman, Dr Mohan’s Diabetes Specialities Centre, Chennai.

What are benefits for the heart

Studies showed that Rybelsus can prevent heart attack and stroke by reducing inflammation. “We know that inflammation can affect the lining of your heart or valves, the heart muscle, or the tissue around the heart. The mechanisms by which it does so are several. High blood sugar levels result in sustained damage to the blood vessels in your heart, making them more likely to develop fatty deposits. Inflammation leads to oxidative stress, or an imbalance between free radicals and antioxidants that damages cells, proteins and DNA. Endothelial stress, or the damage to the lining of blood vessels, may lead to clotting and dislodging of plaques. Now Rybelsus has been found to impact all these mechanisms,” says Dr Mohan.

Inflammation also leads to irregular heartbeats or arrhythmia, heart failure and coronary heart disease. “Inflammation reduction is a key factor in reducing the risk of major cardiovascular events. Studies have shown us that people with Type 2 diabetes are likely to die from heart strokes and heart failure. There is evidence that Rybelsus can help reduce LDL (low-density lipoprotein) cholesterol, along with total cholesterol and triglycerides. It can make platelets less sticky and has a mild diuretic action, which is beneficial for high blood pressure (BP) and heart failure,” says Dr M Sudhakar Rao, consultant, Cardiology, Manipal Hospital, Bengaluru.

How to manage side effects?

As gastrointestinal side effects are similar to other drugs in this class, Dr Mohan suggests that Rybelsus be started in small doses and escalated slowly. “Most patients are able to tolerate the drug if dose escalation is done scientifically,” he says.

He also suggests caution in the protocol. “Take Rybelsus on an empty stomach with 50 ml to 100 ml of water. No more, no less. Otherwise absorption would get affected. Do not take food or any other drug 30 minutes after taking the drug. This is useful for people who hate injectables that are weekly. Oral doses are to be taken daily because of lower bioavailability compared to jabs,” explains Mohan.