A new analysis found that different GLP-1 medications and doses can have different effects on weight, blood sugar, blood pressure, and cholesterol.
Higher-dose treatments generally showed broader improvements across multiple measures of cardiometabolic health.
The findings could eventually help doctors choose GLP-1 treatments based on a patient’s individual health goals — not just weight loss.
GLP-1 medications have become closely associated with weight loss, but their effects can extend beyond the number on the scale. New research suggests that different GLP-1 drugs and doses may offer different advantages when it comes to other measures of heart and metabolic health.
Researchers from the University of Pennsylvania, Yale School of Medicine, and UT Southwestern Medical Center analyzed data from 19 randomized controlled trials involving 13,117 adults with overweight or obesity. They compared oral and injectable GLP-1 receptor agonists to see how they performed across several measures of cardiometabolic health.
The researchers say the findings could eventually support a more personalized approach to choosing these medications. Rather than there being one GLP-1 treatment that is considered best for everyone, the choice could depend partly on which health outcomes are most important for an individual patient.
“We hope that clinicians are encouraged by this study to take a more comprehensive and individual approach to treatment selection,” senior author Yong Chen, PhD, said in a news release.
“For patients, the key message is that there may not be a single ‘best’ GLP-1 therapy for everyone, and it all could really depend on what their individual goals and needs are.”
How researchers compared the medications
For the analysis, researchers searched PubMed, Embase, and CENTRAL for randomized controlled trials published between January 2014 and November 2025. The studies evaluated three GLP-1 receptor agonists — semaglutide, liraglutide, and orforglipron — in adults with overweight or obesity, both with and without type 2 diabetes.
The researchers created a measure called the Cardiometabolic Efficacy Index, or CEI, to compare the treatments. The index ranges from 0 to 1, with higher scores representing a stronger overall performance across seven measures: body-weight reduction, waist circumference, HbA1c, systolic blood pressure, triglycerides, HDL cholesterol, and LDL cholesterol.
The analysis used a network meta-analysis, allowing researchers to compare treatments using evidence from multiple trials. The researchers also looked separately at the individual measures included in the CEI.
Different drugs showed different strengths
Semaglutide at 7.2 milligrams had the highest overall CEI, at 0.86. It was followed by orforglipron at 36 milligrams, with a CEI of 0.68, and semaglutide at 2.4 milligrams, with a score of 0.66. All three produced placebo-adjusted weight reductions of at least 10% on average.
But the overall rankings don't tell the whole story. Orforglipron showed stronger effects on blood sugar control, HDL cholesterol, and systolic blood pressure, while semaglutide showed larger effects on body weight, waist circumference, and LDL cholesterol.
The study also found that oral GLP-1 treatments could perform competitively with injectable options. Among adults without type 2 diabetes, orforglipron 36 milligrams had a CEI of 0.67, compared with 0.63 for oral semaglutide at 25 milligrams.
For consumers, the findings don't mean one medication should automatically be chosen over another. The researchers note that the CEI measures relative performance across several risk factors and does not establish differences in actual cardiovascular outcomes.
“As obesity treatment becomes increasingly personalized, clinicians are often choosing among several highly effective therapies rather than deciding whether to treat at all,” co-author Yuan Lu said in the release.
“Considering blood pressure, cholesterol, and glucose control together could be key to aligning with each patient’s overall, individualized cardiometabolic profile.”