GLP-1 Receptor Agonists for Heart Health in Mild Overweight

New Evidence on GLP-1 Receptor Agonists and Heart Risk

Adults with a body mass index (BMI) between 25 and 26.9 may face cardiovascular risks comparable to patients who currently qualify for glucagon-like peptide-1 receptor agonists (GLP-1 RAs). This finding comes from an observational analysis presented at the European Association for the Study of Diabetes (EASD) annual meeting in Milan, Italy.

Under current guidelines, medications like semaglutide and tirzepatide are approved for weight loss in adults with a BMI of 30 or higher. They are also approved for those with a BMI of 27 or higher who have at least one weight-related complication, such as dyslipidemia or high blood pressure. People with a BMI between 25 and 26.9 remain excluded from these indications.

Dr. Karen Hvid and colleagues from Copenhagen University Hospital in Herlev, Denmark, evaluated whether individuals in this lower bracket who exhibit elevated remnant cholesterol or low-grade inflammation should also be considered for treatment to protect heart health.

Coronary Heart Disease Rates in the Study Cohort

Elevated remnant cholesterol and low-grade inflammation increased coronary risk to levels seen in patients who already meet GLP-1 RA prescribing guidelines. The researchers analyzed data from 313,145 individuals in the UK Biobank and the Copenhagen General Population Study (CGPS). All participants had a BMI of 25 or higher, a median age of 58, were approximately 50 percent female, and had no baseline diabetes or heart disease.

Over follow-up periods reaching up to 15 years in the UK Biobank and 18 years in the CGPS, 23,134 participants developed coronary heart disease. Approximately two-thirds of the total cohort met current GLP-1 RA eligibility rules.

Among participants with a BMI of 25 to 26.9, roughly half had high remnant cholesterol, low-grade inflammation, or both. In the CGPS, individuals with both markers had a 41 percent higher risk of coronary heart disease than peers with normal levels. In the UK Biobank, the risk was 47 percent higher.

Remnant Cholesterol and Inflammation as Risk Factors

Remnant cholesterol refers to the cholesterol content of circulating lipoproteins that are neither high-density lipoprotein (HDL) nor low-density lipoprotein (LDL). Both remnant cholesterol and chronic low-grade inflammation occur frequently in overweight individuals and contribute to arterial disease.

The comparison group of participants who met current drug indications showed an increased heart disease risk of 41 percent in the CGPS and 35 percent in the UK Biobank. The presence of these two metabolic markers produced a similar risk profile regardless of whether a patient met the current BMI cutoffs.

GLP-1 RAs are known to lower cholesterol and reduce inflammatory markers while decreasing the incidence of heart attacks and strokes. The authors stated that these biological effects provide a rationale for reconsidering access criteria.

Study Limitations and the Need for Clinical Trials

This research relies on observational cohort data and does not prove that administering GLP-1 RAs to people with a BMI of 25 to 26.9 will prevent cardiovascular events. Observational studies identify associations across populations rather than confirming drug efficacy.

Dr. Hvid emphasized that randomized clinical trials must test this intervention directly before medical organizations or regulators update prescribing indications. For now, individuals managing their cardiovascular risk can discuss remnant cholesterol and inflammation markers with their physician to evaluate their overall metabolic health.