New Antiobesity Drugs Will Benefit Many. Is That Bad?

The biased discourse and double standards around antiobesity glucagon-like peptide 1 (GLP-1) receptor agonists continue apace, most recently in The New England Journal of Medicine (NEJM) where some economists opined that their coverage would be disastrous for Medicare.

Among their concerns? The drugs need to be taken long term (just like drugs for any other chronic condition). The new drugs are more expensive than the old drugs (just like new drugs for any other chronic condition). Lots of people will want to take them (just like highly effective drugs for any other chronic condition that has a significant quality-of-life or clinical impact). The UK recommended that they be covered only for 2 years (unlike drugs for any other chronic condition), as reported on Medscape UK. And the Institute for Clinical and Economic Review (ICER) on which they lean heavily decided that $13,618 annually was too expensive for a medication that leads to sustained 15%-20% weight losses and those losses' consequential benefits.

As a clinician working with patients who sustain those levels of weight loss, I find that conclusion confusing. Whether by way of lifestyle alone, or more often by way of lifestyle efforts plus medication or lifestyle efforts plus surgery, the benefits reported and seen with 15%-20% weight losses are almost uniformly huge. Patients are regularly seen discontinuing or reducing the dosage of multiple medications as a result of improvements to multiple weight-responsive comorbidities, and they also report objective benefits to mood, sleep, mobility, pain, and energy. Losing that much weight changes lives. Not to mention the impact that that degree of loss has on the primary prevention of so many diseases, including plausible reductions in many common cancers — reductions which have been shown to occur after surgery-related weight losses and for which there's no plausible reason to imagine that they wouldn't occur with pharmaceutical-related losses.

Are those discussions found in the NEJM op-ed or in the ICER report? Well, yes, sort of. However, in the NEJM op-ed, the word "prevention" isn't used once, and unlike with oral hypoglycemics or antihypertensives, the authors state that with antiobesity medications, additional research is needed to determine whether medication-induced changes to A1c, blood pressure, and waist circumference would have clinical benefits: "Antiobesity medications have been shown to improve the surrogate end points of weight, glycated hemoglobin levels, systolic blood pressure, and waist circumference. Long-term studies are needed, however, to clarify how medication-induced changes in these surrogate markers translate to health outcomes."

Primary prevention is mentioned in the ICER review, but in the "limitations" section where the authors explain that they didn't include it in their modelling: "The long-term benefits of preventing other comorbidities including cancer, chronic kidney disease, osteoarthritis, and sleep apnea were not explicitly modeled in the base case."

And they pretended that the impact on existing weight-responsive comorbidities mostly didn't exist too: "To limit the complexity of the cost-effectiveness model and to prevent double-counting of treatment benefits, we limited the long-term effects of treatments for weight management to cardiovascular risk and delays in the onset and/or diagnosis of diabetes mellitus."

As far as cardiovascular disease (CVD) benefits go, you might have thought that it would be a slam dunk on that basis alone, at least according to a recent simple back-of-the-envelope math exercise presented at a recent American College of Cardiology conference, which applied the semaglutide treatment group weight changes in the STEP 1 trial to estimate the population impact on weight and obesity in 30- to 74-year-olds without prior CVD, and estimated 10-year CVD risks utilizing the BMI-based Framingham CVD risk scores. By their accounting, semaglutide treatment in eligible American patients has the potential to prevent over 1.6 million CVD events over 10 years.

Finally, even putting aside ICER's admittedly and exceedingly narrow base case, what lifestyle-alone studies could ICER possibly be comparing with drug efficacy? And what does "alone" mean? Does "alone" mean with a months- or years long interprofessional behavioral program? Does "alone" mean by way of diet books? Does "alone" mean by way of simply "moving more and eating less"? I'm not aware of robust studies demonstrating any long-term meaningful, predictable, reproducible, durable weight loss outcomes for any lifestyle-only approach, intensive or otherwise.

It's difficult for me to imagine a situation in which a drug other than an antiobesity drug would be found to have too many benefits to include in your cost-effectiveness analysis but where you'd be comfortable to run that analysis anyhow, and then come out against the drug's recommendation and fearmonger about its use.

But then again, systemic weight bias is a hell of a drug.

Follow Yoni Freedhoff on Twitter @YoniFreedhoff

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Any views expressed above are the author's own and do not necessarily reflect the views of WebMD or Medscape.

Cite this: New Antiobesity Drugs Will Benefit Many. Is That Bad? - Medscape - Mar 31, 2023.