Copenhagen University Hospital Researchers Evaluate GLP-1 RAs for Overweight
New epidemiological data presented between September 28 and October 2 at the annual meeting of the European Association for the Study of Diabetes in Milan, Italy, indicate that expanding the clinical indication for GLP-1 receptor agonists could protect millions of overweight individuals from heart disease. Researchers from Copenhagen University Hospital evaluated large-scale data to determine whether patients with a body mass index between 25 and 26.9—currently ineligible for weight-loss indications unless comorbid conditions are present—experience cardiovascular risk profiles comparable to eligible cohorts.
- Data presented at the EASD annual meeting suggest extending GLP-1 receptor agonist indications to approximately half of individuals with a body mass index of 25 to 26.9 who exhibit specific metabolic risk factors.
- Analysis of 313,145 individuals across the UK Biobank and Copenhagen General Population Study demonstrated that overweight participants with high remnant cholesterol or low-grade inflammation face a coronary heart disease risk equivalent to those currently eligible for the drugs.
- Investigators from Copenhagen University Hospital emphasize that dedicated clinical trials are now required to confirm whether administering semaglutide or tirzepatide to this expanded subpopulation effectively mitigates cardiovascular events.
Evaluating Cardiovascular Risk Below Current Thresholds
Current regulatory approvals restrict GLP-1 receptor agonists such as semaglutide and tirzepatide for weight management to adults with a body mass index of 30 or higher, or a body mass index of 27 accompanied by weight-related comorbidities like dyslipidaemia, high blood pressure, type 2 diabetes, or established cardiovascular disease. Individuals registering a body mass index between 25 and 26.9 remain excluded from these prescriptions despite occupying the clinical overweight category. To test the validity of this threshold, Dr. Karen Hvid and colleagues at Copenhagen University Hospital analyzed data to compare coronary heart disease incidence across these populations.
The investigation utilized prospective health data drawn from 313,145 participants across the UK Biobank and the Copenhagen General Population Study. These individuals presented with a median age of 58, were approximately 50 percent female, and had no prior history of diabetes or coronary heart disease at baseline. Tracking periods spanned upwards of ten years, reaching up to 15 years in the UK Biobank and 18 years in the Copenhagen General Population Study. Throughout these extended follow-ups, 23,134 participants developed coronary heart disease, an endpoint encompassing diagnoses, myocardial infarctions, coronary artery bypass procedures, percutaneous coronary interventions, or cardiovascular deaths.
Biomarkers of Inflammation and Cholesterol Reveal Equal Hazard Rates
The study specifically examined chronic low-grade inflammation and remnant cholesterol, denoting lipid fractions excluding high-density and low-density lipoproteins. Both biological markers frequently accompany excess weight and independently increase the risk of heart disease. Among the 313,145 total participants, roughly two-thirds—totaling 204,850 individuals—met standard eligibility criteria for GLP-1 receptor agonists. More than 90 percent of those excluded fell into the body mass index range of 25 to 26.9.
Subgroup analysis revealed that approximately half of the individuals within the 25 to 26.9 body mass index bracket—specifically 44 percent in the Copenhagen General Population Study and 48 percent in the UK Biobank—displayed elevated remnant cholesterol, low-grade inflammation, or a combination of both. Statistical evaluation established that these ineligible participants faced a risk of coronary heart disease matching those who qualified under current prescribing guidelines. Individuals lacking a standard GLP-1 receptor agonist indication but presenting with both elevated remnant cholesterol and low-grade inflammation exhibited a 41 percent higher risk of cardiovascular disease in the Copenhagen cohort and a 47 percent higher risk in the UK Biobank cohort, compared to peers with healthy inflammatory and lipid markers. These figures closely mirrored the elevated risk observed in conventionally eligible participants, which registered at 41 percent and 35 percent in the respective cohorts.
Implications for Clinical Practice and Future Trial Design
Therapeutic agents in this class are recognized for their capacity to lower circulating lipids, reduce systemic inflammation, and decrease the incidence of myocardial infarction and stroke. Because a substantial fraction of individuals with a body mass index between 25 and 26.9 carry biochemical risk markers that drive cardiovascular morbidity at rates identical to heavier patient populations, researchers argue for a reassessment of current prescribing boundaries.
As Dr. Karen Hvid noted during the presentation in Milan, roughly half of all people registering a body mass index between 25 and 26.9 possess cholesterol or inflammatory profiles that heighten their vulnerability to cardiac events, matching the risk profile of individuals currently cleared for pharmacotherapy. Translating these epidemiological insights into revised clinical practice guidelines will require prospective trials to establish safety and efficacy in this newly identified at-risk demographic.
Disclaimer: The information provided in this article is for educational and scientific communication purposes only and does not constitute medical advice. Always consult with a qualified healthcare provider regarding any medical condition, diagnosis, or treatment plan.