New research being presented at the annual meeting of the European Association for the Study of Diabetes (EASD) in Milan, Italy (Sept 28 – Oct 2) makes a case for extending the indication for GLP1- receptor agonists (GLP1-RAs) to millions more people, to protect their heart health.
The GLP1-RA drugs semaglutide and tirzepatide are approved for weight loss in adults with a BMI of ≥30 or a BMI of ≥27 plus at least one weight-related health condition e.g. dyslipidaemia (unhealthy levels of cholesterol or other fats in the blood), high blood pressure, type 2 diabetes or previous cardiovascular disease.
Individuals with a BMI of 25-26.9 are not eligible, despite being in the overweight range. The Danish analysis of data on hundreds of thousands of people in the UK and Denmark provides evidence for extending the indication to include about half of those in this group, to cut their risk of heart disease.
In this study, the first of its kind, Dr Karen Hvid, of Copenhagen University Hospital, Herlev, Denmark, and colleagues compared the risk of coronary heart disease in individuals with a BMI of 25-26.9 and high remnant cholesterol and/or low-grade inflammation with that of individuals who were eligible for GLP-1 RAs for weight loss. Chronic low-grade inflammation and remnant cholesterol (the term used to describe cholesterol that isn't HDL or LDL) both increase the risk of heart disease and are common in people with overweight.
Two large prospective studies, the UK Biobank and the Copenhagen General Population Study (CGPS), provided data on 313,145 individuals with overweight, defined as a BMI of 25 or above (median age 58, approx. 50% female) who were free of coronary heart disease and diabetes.
During the follow-up period of more than ten years (up to 18 years in the CGPS and up to 15 years in the UK Biobank), 23,134 developed coronary heart disease, defined as having a diagnosis, a heart attack, a coronary artery bypass, a percutaneous coronary artery intervention (a procedure to open a narrowed or blocked artery) or cardiovascular death.
About two-thirds of the participants (204,850) were eligible for GLP1-RAs under the current indication.
More than 90% of those not eligible had a BMI of 25-26.9 and approximately half of those with a BMI of 25-26.9 (44% in the CGPS and 48% in the UK Biobank) had either high remnant cholesterol, low-grade inflammation or both.
Analysis of the data showed the participants who weren't covered by the indication but had high remnant cholesterol, low-grade inflammation or both were just as likely to develop coronary heart disease as those who were eligible for the drugs.
For example, individuals without a GLP-1 RA indication but elevated remnant cholesterol and low-grade inflammation were 41% (CGPS study) and 47% (UK Biobank) more likely to develop cardiovascular disease than those without an indication and healthy levels of cholesterol and inflammation.
This compares with an increased risk of heart disease of 41% among those in the CGPS study with an indication and 35% in those in the UK Biobank study with an indication.
We know that GLP-1 RAs can cut cholesterol and inflammation and reduce the risk of heart attacks, strokes and other cardiovascular problems."
Dr. Karen Hvid, Copenhagen University Hospital
"We found that about half of people with a BMI of 25-26.9 had levels of cholesterol and/or inflammation that increased their risk of heart problems.
"They had a similar risk of coronary heart disease as those who were eligible for GLP1-RAs for weight loss – but, as things stand, they would not be prescribed them.
"Our study makes the case for extending the indication to this group. Clinical trials are now needed."
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