Ask which GLP-1 medication is “best” and most answers default to whichever one lost the most weight in its own trial. A study published this July tried something different: putting several drugs and doses on the same scorecard, measured against seven markers of heart and metabolic health instead of the scale alone. The result is a more useful way to think about these medications — and a good example of how a clever methodology can still get oversold.
What the researchers did
A team from the University of Pennsylvania, Yale, and UT Southwestern pooled data from 19 randomized controlled trials covering 13,117 adults with overweight or obesity. Rather than comparing weight loss percentages alone, they built something new: the Cardiometabolic Efficacy Index (CEI), a 0-to-1 score combining seven measures — body weight, waist circumference, HbA1c (a blood sugar marker), systolic blood pressure, triglycerides, HDL cholesterol, and LDL cholesterol.
Scored against that index:
- Injectable semaglutide at 7.2 mg — the higher dose cleared for use in 2026 — scored highest at 0.86.
- Orforglipron, an oral medication, scored 0.68 at its 36 mg dose.
- Injectable semaglutide at the older 2.4 mg dose scored 0.66.
All three delivered at least 10% average body weight reduction in their respective trials. But the index surfaced differences beyond the scale: orforglipron scored particularly well on blood sugar control and blood pressure, while semaglutide’s advantage showed up more in weight, waist circumference, and LDL cholesterol. Oral semaglutide performed comparably to the injectable forms in the trials that tested it head-to-head. Senior author Yong Chen summed up the takeaway for clinicians: there may not be a single “best” GLP-1 therapy — the right one depends on which of those seven markers matters most for a given patient.
What this does not establish
The framing is useful. The underlying comparison has real limits, and they matter more than the headline number.
This is a cross-trial comparison, not a head-to-head trial. The 19 studies feeding into the CEI were not all testing the same population, the same follow-up length, or the same protocol against each other. Semaglutide 7.2 mg scoring higher than orforglipron 36 mg does not mean a trial randomized the same group of people to one or the other and measured a winner. It means each drug performed well in its own separate trial population, and the index is a way of putting those separate results on a common scale — a genuinely useful tool, but not a substitute for a real comparative trial.
The index itself is new. The CEI was created by this research team for this analysis. It is not an established clinical endpoint that other studies have validated over time, and weighting all seven markers equally is a judgment call — one that may not match what matters most for your own health picture. A patient whose main concern is blood pressure and a patient whose main concern is LDL cholesterol could reasonably weigh the same data differently than the index does.
A trial average is not a prediction for you. Even setting the cross-trial issue aside, every number here is a population average from a clinical trial. Individual results inside those same trials varied widely around each average. Nothing in this study tells you where you would land.
The part that applies to compounded medications
Every drug and dose in this comparison — semaglutide, including the newer 7.2 mg dose, and orforglipron, sold under the brand name Foundayo — is an FDA-approved, manufactured branded product tested in the trials described above. That evidence belongs to those specific manufactured products.
Compounded semaglutide and tirzepatide, the medications NoBsRx provides provider-guided access to, are prepared by state-licensed pharmacies for an individual patient. They are not FDA-approved products, and they were not part of this analysis or the trials feeding into it. A compounded preparation is not automatically equivalent to the manufactured version it is modeled on, and none of the CEI scores above can be assumed to transfer to it. If a telehealth company points to a comparison like this one as proof of what their compounded product does, they are citing evidence for a different product than the one they are selling you.
Why this framing matters more than the score
The actual news here isn’t that one number beat another number. It’s that “GLP-1 medications” stopped being one interchangeable category the moment there were enough drugs and doses on the market to meaningfully differ from each other — in side effect profile, in which lab markers move most, in whether a pill or an injection fits someone’s life better.
That’s a case for individualized review, not a case for picking the drug with the highest number on a chart. It’s also the argument for working with a licensed provider who looks at your labs, your history, and your goals before recommending anything — rather than a one-size dose recommendation based on a trial population you weren’t part of.
It’s part of why we publish every program price up front rather than routing you through a quiz first. Which medication and dose fit you is a clinical question; what it costs shouldn’t be a surprise waiting at the end of one.
This post is general information, not medical advice. It does not describe a guaranteed benefit or outcome of any NoBsRx program. Compounded medications are not FDA-approved. Treatment is never guaranteed — eligibility, diagnosis, and every treatment decision are made by independent licensed providers based on an individual clinical assessment, and availability varies by state. Do not start, stop, or change any medication based on an article. Talk to a licensed provider about what fits your own health history.