The popular weight-loss medicine semaglutide might be protecting the heart in ways other than just weight loss, according to the results of a trial recently published in The Lancet. Last year, the medicine was approved for reducing the risk of cardiovascular deaths, heart attacks and brain strokes.
With obesity being a major risk factor for heart diseases, the incredible weight-loss reported by obese individuals on the medicine was thought to be the reason behind fewer major adverse cardiovascular events seen in them. Yet, the new study shows that this protection for the heart was seen irrespective of a person’s body weight at initiation and how much weight they lost with the medicine.
What did the study show?
The study is based on the data of over 17,600 patients with obesity, but without diabetes, from across 41 countries.
First, the researchers observed a four per cent decline in the risk of heart disease for every 5 kg loss of weight or 5 cm smaller waist. This protection to the heart offered by semaglutide has already been established. What was interesting is that the researchers found that this risk reduction was not directly linked to the weight lost by the participants.
This takes us to the second finding. The researchers found that this risk reduction for heart diseases was not linearly associated with the initial weight of the participants or with how much weight the participants lost.
Third, the researchers noted that the reduction in waist circumference was somewhat linked to the protection offered by the drug. The changes in the waist circumference — considered to be an indicator of how much fat is stored in the organs — accounted for around 33 per cent of the reduction in cardiovascular events observed.
Why is this significant?
These findings are significant because it means that the protection to the heart offered by semaglutide is not just due to the dramatic weight loss experienced by those on the medicine. People on semaglutide can lose up to 15 per cent or 17 per cent of their body weight.
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Semaglutide, which mimics one sugar-regulating hormones, and other drugs such as tirzepatide, which mimics two such hormones, have either been approved or have been found to be effective for conditions other than diabetes or weight loss, such as heart diseases, obstructive sleep apnea, chronic kidney disease or fatty liver. But, most of the impact is thought to be because of underlying obesity, which is also one of the major risk factors for these conditions.
The researchers say that the drug may be working by mechanism other than weight loss or control of blood glucose levels. So, they say that semaglutide and perhaps other GLP-1 medicines should be considered to be disease-modifying drugs — a therapy that changes the way a disease affects the body instead of just treating the symptoms.
Dr Anoop Misra, chairman of Fortis C-DOC for Endocrinology, says, “It is important that this study suggests that semaglutide works through pathways other than weight loss — direct effects on blood vessels, inflammation reduction, blood pressure control and lipid improvements. If that is the case, prescribing restrictions based on BMI (body mass index) thresholds or weight-loss targets may not be appropriate.”
How will this change the prescription of the drug?
Dr Misra says that because the drug may protect the heart irrespective of the weight at which a person initiates treatment or how much weight loss they are experiencing, the drug may help even those with lower BMI. He adds, overweight or obese people might benefit regardless of whether they lose weight — some patients put on the medication do not end up losing weight.
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Dr Misra says, importantly, the researchers observed a 33 per cent benefit when it comes to reduction of adverse events of the heart when the waist circumference went down. “This may be beneficial for Indians where abdominal obesity (including fat under the skin, inside abdomen and in other areas) is widespread.” Indians are known to be at a higher risk of heart diseases because of fat accumulation in the abdomen.
While it is an encouraging trend, the challenge — as the researchers themselves pointed out — is that the study population was predominantly white and male. This means the trend, especially concerning abdominal obesity, might not hold true in an Indian population. Additionally, the analysis of the impact across different groups with weight and waist sizes was not done against a similarly matched group of people not on the treatment, meaning other factors such as lifestyle or genetics might have influenced the results.
