Will the Cheaper Weight Loss Regimens Replace GLP-1 Drugs?

When patients start on the latest obesity drugs, they often experience reduced food cravings and significant weight loss. However, discontinuing these drugs usually reverses these effects: cravings return, and so does the weight. For instance, within a year of stopping semaglutide — known as Wegovy or Ozempic — people typically regain about two-thirds of the weight they lost. Tirzepatide, marketed as Zepbound or Mounjaro, shows similar patterns. This has led to the medical consensus that these obesity drugs need to be taken indefinitely, perhaps for life.

For pharmaceutical companies selling these blockbuster drugs, collectively known as GLP-1 drugs after the hormone they mimic, this is a lucrative prospect. For patients, who might be paying over $1,000 a month out of pocket, it’s a different story. Most Americans simply can’t afford such ongoing expenses, as a recent article in The Atlantic outlines.

Finding cheaper alternatives

This financial burden has prompted some doctors to get creative, developing regimens that substitute cheaper, though less well-known, alternatives. GLP-1 drugs are highly effective, promoting more rapid weight loss than any other obesity medications currently available.

However, some doctors are exploring whether these drugs need to be used permanently. “What if we use them short-term, for six months to a year, to lose 50 pounds?” asks Sarah Ro, an obesity-medicine doctor and director of the University of North Carolina Physicians Network Weight Management Program. She and other doctors are investigating transitioning patients to older, less expensive drugs for long-term maintenance.

Dr. Ro has already helped hundreds of patients make this switch out of necessity. Many of her patients in rural North Carolina lack insurance coverage for the new obesity drugs and can’t afford them out of pocket. When North Carolina’s state employee health insurance cut off coverage for GLP-1 drugs in April, Ro transitioned her patients to older medications like topiramate, phentermine, metformin, and bupropion/naltrexone, coupled with lifestyle counseling. These alternatives are generally less effective, leading to about half the weight loss of GLP-1 drugs, but are far more affordable, costing as little as $10 a month when prescribed as generics.

Retirees on Medicare lose GLP-1 drug coverage

Jamy Ard, an obesity medicine doctor at Wake Forest University School of Medicine, also had to adjust his approach for patients who lost GLP-1 drug coverage upon retiring and switching to Medicare, which currently does not cover obesity treatments. Doctors like Ard see the need for research on transitioning from GLP-1 drugs to older ones, as many patients will lose coverage at retirement age. “Now I’ve got to figure out, well, how do I treat them?” he said.

Are the alternatives safe?

Long-term data on older drugs are sparse, largely because obesity drugs weren’t profitable enough to justify expensive, long-term studies until recently. Switching from GLP-1 drugs to older medications is largely anecdotal at this point, with varying outcomes. A small minority can maintain their weight with just diet and exercise, while others find the older drugs ineffective. Dr. Ro’s experience suggests that 50% to 60% of her patients have successfully maintained weight loss using older drugs alongside lifestyle changes like cutting out fast food and sugary drinks.

A tailored trial-and-error approach is the way to go

The choice of alternative medication depends on the patient. Different drugs target different biological pathways. For example, the combination of naltrexone and bupropion reduces the pleasure of eating and is particularly effective for emotional eaters. Topiramate makes carbonated drinks unpleasant, which can help soda drinkers. Each drug has different side effects, requiring a tailored approach and sometimes trial and error to find the best fit.

Doctors are also finding that some patients can maintain their weight on lower or less frequent doses of GLP-1 drugs. Lowering the dose doesn’t save money since the pens cost the same regardless of dosage, but extending the time between doses can help stretch supplies.

Stopping completely might be a challenge

Complete discontinuation of obesity medications, GLP-1 or otherwise, is unlikely for most patients. Weight loss triggers compensatory mechanisms in the body, evolved to prevent starvation, making long-term maintenance a constant challenge. Susan Yanovski, co-director of the NIH’s Office of Obesity Research, describes long-term weight maintenance as the “holy grail” of obesity treatment.

The best maintenance strategy — whether it involves GLP-1 drugs, and at what dose — remains an individual question needing further study. “These are really good research questions,” Yanovski said, though they might not align with the pharmaceutical companies’ focus on developing new drugs.

Compounded semaglutide is announced

Hims & Hers company announced last week that it will be selling compounded semaglutide for weight loss at prices significantly lower than Wegovy and Ozempic, addressing a gap in supply. However, it’s important to note that compounded semaglutide is not FDA-approved and undergoes less extensive testing than brand-name drugs.

This compounded GLP-1 drug will be prescribed by physicians through their telehealth platform. Prices start at $79 per month for oral medication kits and $199 per month for injections, much lower than the list prices of Ozempic ($935.77) and Wegovy ($1,349.02).

However, compounded semaglutide differs from FDA-approved drugs like Wegovy and Ozempic in several key ways. Compounded medications do not undergo the rigorous FDA approval process, which ensures safety, efficacy, and quality through extensive testing. This lack of testing can lead to concerns about inconsistent potency, bioavailability, and safety.

Also, these drugs can vary in how they are absorbed and utilized by the body, potentially leading to unpredictable therapeutic outcomes. Safety concerns also arise from the sterility and cleanliness of the compounding process, which might introduce harmful contaminants if not properly managed.

The BrainWeighve app would be an ideal off ramp…

The ability to rechannel displacement into less harmless activities rather than succumbing to urges is behind the behavior modification app, BrainWeighve, currently ramping up for a trial through the University of California Los Angeles (UCLA). The trial focuses on weight loss for obese teens using a self-directed, physician-supervised program withdrawing from one problem food at a time.”

Your responses and feedback are welcome!

Source: “Ozempic Patients Need an Off-Ramp,” The Atlantic, 5/22/24
Source: “Hims & Hers Selling GLP-1 Weight Loss Drugs Like Wegovy for 85% Less: What to Know,” Healthline.com, 5/22/24
Image by Thought Catalog on Unsplash

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OVERWEIGHT: What Kids Say explores the obesity problem from the often-overlooked perspective of children struggling with being overweight.

About Dr. Robert A. Pretlow

Dr. Robert A. Pretlow is a pediatrician and childhood obesity specialist. He has been researching and spreading awareness on the childhood obesity epidemic in the US for more than a decade.
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Presentations

Dr. Pretlow’s invited presentation at the American Society of Animal Science 2020 Conference
What’s Causing Obesity in Companion Animals and What Can We Do About It

Dr. Pretlow’s invited presentation at the World Obesity Federation 2019 Conference:
Food/Eating Addiction and the Displacement Mechanism

Dr. Pretlow’s Multi-Center Clinical Trial Kick-off Speech 2018:
Obesity: Tackling the Root Cause

Dr. Pretlow’s 2017 Workshop on
Treatment of Obesity Using the Addiction Model

Dr. Pretlow’s invited presentation for
TEC and UNC 2016

Dr. Pretlow’s invited presentation at the 2015 Obesity Summit in London, UK.

Dr. Pretlow’s invited keynote at the 2014 European Childhood Obesity Group Congress in Salzburg, Austria.

Dr. Pretlow’s presentation at the 2013 European Congress on Obesity in Liverpool, UK.

Dr. Pretlow’s presentation at the 2011 International Conference on Childhood Obesity in Lisbon, Portugal.

Dr. Pretlow’s presentation at the 2010 Uniting Against Childhood Obesity Conference in Houston, TX.

Food & Health Resources