In fact, research shows that the weight tends to return more quickly after stopping anti-obesity medications than after completing behavioral programs—reinforcing concerns that transient GLP-1 use without sustained lifestyle modifications is likely to undermine long-term outcomes.
Here, dietary supplements may find opportunity in accepting a supporting role as part of a lifestyle approach, particularly if GLP-1 drug use is treated as a training window rather than a quick fix or lifetime commitment and contextualized within a continuum of metabolic myth cycles.
“This pattern of weight regain is not in any way exclusive to our new treatments,” said Jacqueline Jacques, naturopathic doctor and fellow of the Obesity Society. “Scientists and clinicians studying obesity have known for decades that effective weight loss will be followed by weight regain that typically becomes easier with every successive attempt at weight loss.”
And while downsizing in the GLP-1 era carries similar risks to any rapid weight loss approach, it distinguishes itself from the fat-phobia of the 1990s and the carb-insulin panic of the 2010s through its established mechanisms of action and a biological regulation narrative. It also frames obesity more as a chronic disease requiring chronic treatment.
Weight regain and reversal of benefits
According to a review published earlier this year in the British Medical Journal (BMJ), the average rate of weight regain is 0.4 kg (.88 lbs)/month after stopping treatment at an average of 39 weeks, with weight and risk markers for diabetes and heart disease predicted to return to pre-treatment levels in less than two years. It also reported that weight returns nearly four times faster than after diet and physical activity changes, regardless of the amount lost during treatment.
“This evidence suggests that despite their success in achieving initial weight loss, these drugs alone may not be sufficient for long term weight control,” the researchers from the University of Oxford noted. “These findings suggest caution in short-term use of these drugs without a more comprehensive approach to weight management.”
In an associated editorial, Qi Sun, associate professor of medicine at Brigham and Women’s Hospital and Harvard Medical School, highlighted that obesity is not a disease that can be easily treated and managed and that the BMJ study findings cast doubt on the notion that GLP-1 receptor agonists are a perfect cure.
He also noted that individuals with a healthy body mass index who turn to GLP-1s run the risk of “fat overshooting,” whereby they lose more lean mass than people with obesity and, upon regaining weight, experience a faster increase in fat mass than lean mass.
“GLP-1 receptor agonists should not be relied on as a magic cure for treating obesity,” he recommended. “While considerable weight loss, even if temporary, may still bring some health benefits for those with obesity, people using GLP-1 receptor agonists should be aware of the high discontinuation rate and the consequences of cessation of medications. Healthy dietary and lifestyle practices should remain the foundation for obesity treatment and management, with medications such as GLP-1 receptor agonists used as adjuncts.”
With an estimated half of people with obesity discontinuing weight loss drugs within 12 months, both academia and industry are taking a closer look at not only how best to support nutrient needs during the weight loss journey but how to help people adjust or transition to a new, healthier lifestyle.
Prevalence and consequence of obesity
Obesity is a chronic and relapsing condition affecting amost two billion adults and 160 million children (age 5 to 19) worldwide, according to the most recent World Health Organization fact sheet. In the United States, the prevalence of obesity has reached over 40% in U.S. adults and nearly 23% of children, with over 50% of adults worldwide predicted to be obese or overweight by 2050.
It is recognized as a complex disease influenced by genetics, environment, high-calorie food availability, physical inactivity, stress and lack of sleep and is a key risk factor for chronic diseases, including hypertension and diabetes
Prepping during the GLP-1 training window
Successful off-ramping and long-term outcomes also depend on addressing the other perils that present as nutrient deficiency induced by suppressed eating and calorie reduction during the GLP-1 journey.
According to a recent narrative review in Clinical Obesity, which synthesized data from some 460,000 adults on GLP-1 receptor agonists, 2.1 % experienced muscle loss and 12.7% had a new nutritional deficiency diagnosis at six months. Deficiencies identified included vitamin D (7.5%), iron (1.6%), thiamine (.02%), with percentages increased at 12 months.
This creates opportunities not just for industry-darlings protein and fiber to benefit from the uplift of GLP-1 nutritional support positioning but for micronutrients to fill gaps and avoid serious consequences of reduced food intake, slower gastric emptying, altered absorption and dangerous deficiency.
Research published by GNC within the last year explored both vital nutrient deficiencies in GLP-1 users and what supplements they should be taking.
The deficiency study, conducted in a sample of 69 GLP-1 users, reported that participants consumed too many calories and too much saturated fat and sodium but not enough calcium, iron, magnesium, potassium, vitamin A, C, D, E, K, and choline. Fiber, protein, fruits and vegetables were also lacking. Just over half of the study participants indicated that they did not intend to stay on GLP-1s for the long term.
“Participants on a GLP-1RA are not meeting the daily recommended intake for several vital nutrients through their diet or higher protein needs during weight loss,” the GNC researchers wrote in the journal Frontiers in Nutrition. “Patient-centered nutritional guidance is essential to optimize health outcomes and prevent unintended health consequences.”
In April 2024, vitamin and supplement retailer became the first major retailer to launch a GLP-1 support program to fill nutritional gaps and support gastrointestinal, muscle and bone health—the areas most affected by these weight loss drugs.
Speaking at the Weight Management Summit in February, Rachel Kreider, MPH, RD, vice president of product innovation and science at GNC, highlighted the inflammatory state associated with excess fat accumulation in muscle tissue as an important area of opportunity.
“That’s something that is going to allow people to move better so that they can really just get into a healthier space,” she said. “So, when they go off medication, they’re in the habit, they’ve started to protect their lean mass already, and then we can have a better off ramp by making sure we’re instituting those changes during the treatment.”
The GNC research also identified the need for a paradigm shift from adequate intake to optimal intake—where adequate nutrient intake represents the level required to prevent deficiencies and chronic disease and optimal nutrient intake “extends beyond those requirements and considers levels necessary to achieve peak physiological function, provide health benefits and further disease prevention.”
Key GNC takeaways on the potential of supplement strategies to support GLP-1 patients
- Multivitamins, vitamin D and omega-3 or fish oil supplements can fill nutrient gaps from dietary intake, increase suboptimal serum nutrient levels and potentially offer long term health benefits.
- Protein, whey, creatine and HMB supplementation can preserve lean mass while building muscle strength during weight loss.
- Thermogenic, antioxidants and anti-inflammatory dietary supplements can support metabolic function and reduce oxidative stress and inflammatory markers.
- Fiber and probiotic supplements can reduce constipation and improve stool consistency, a common side effect of GLP-1RA.
Supplementing the off-ramp
In response to the rate of discontinuation identified from real-world observation, the BMJ review cautioned against short-term use of weight management medication and emphasized the need for further research into cost effective strategies for long term weight control.
While discussions at the Weight Management Summit highlighted gradually tapering the dose or increasing time between injections as strategy to manage patient withdrawal symptoms and reduce susceptibility to weight regain and sudden appetite spikes, the consensus was that sustaining metabolic change requires additional effort and assistance.
Reverting to previous habits
A year-long Cornell University analysis of 150,000 U.S. households published late last year in The Journal of Marketing Research that linked survey responses with transaction level grocery data found that GLP-1 users initially changed how they shopped for food. Within six months of starting the medication, grocery spending fell 5.3%, with a noticeable curbing of snack, sweet and fast-food purchases.
But the effect proved fragile. Roughly one-third of users who stopped taking GLP1s during the study reverted to their previous spending habits and even ended up with slightly less healthy grocery baskets than before they started, marked by increased spending on candy and chocolate—suggesting that cravings come back stronger.
Brittany Johnson, PhD, RDN, lead author on the GNC studies, noted that although GLP-1 drugs deliver significant weight loss, long-term success depends on sustainable lifestyle support. In that context, supplementation at meaningful doses for meaningful endpoints can play a meaningful role both during and after GLP-1 treatments.
“Supplements can serve as a great tool by helping reinforce support for physiological pathways, such as regulating appetite and blood sugar control which may promote better weight maintenance after GLP-1 drugs,” she said, noting that protein, fiber, thermogenics, caffeine, ALA, berberine and cinnamon have strong meta-analyses data for endpoints including satiety and glycemic control.
In a perspective published this month in The Journal of Nutrition, Johnson focused on the potential complementary—but still to be properly studied—role of fiber-rich foods or supplementation to help reduce side effects during GLP-1 treatment and support appetites, glycemic control and healthy body weight during the off ramp.
“The GLP-1 era has made it clear that there is no lasting solution without long-term lifestyle changes,” she said. “As pharmaceuticals become more powerful, the supplement industry has an even greater responsibility to emphasize sustainability, adherence and lifestyle integration. Neither a drug or dietary supplements work in isolation, and both require consistent habits to support long-term health. I think this challenges our industry to think outside the box to offer protocols alongside supplements to support sustainable habits and invest in high-quality clinical trials.”
Discussing the off-ramp opportunity, Dr. Jacques emphasized that the supplement industry should continue to position products as support products for weight loss maintenance rather than drug alternatives, noting that the pharmaceutical industry is moving aggressively into maintenance and long-term obesity management.
“If we don’t do the science and claim this territory with credibility, it will be taken from us, not because we couldn’t, but because we didn’t,” she said, again highlighting that weight regain is a chronic condition. “The most powerful opportunity for the natural products industry is not competing with drugs on acute weight loss but owning the long-term space of ‘helping to maintain a healthy weight’. Don’t be a drug alternative, be an off-ramp solution/partner.”
Areas of opportunity include supporting increased resting metabolic rate, exercise tolerance, endurance, muscle and bone health, appetite regulation, satiety and micronutrient sufficiency, as well as addressing hormonal, liver, gut, sleep and baseline nutritional issues that can also impair metabolic health.
“Take a page from sports and active nutrition,” Dr. Jacques added, highlighting a white space for endurance, energy and recovery products. “As people start to lose weight, movement becomes easier. I would love to see a new positioning of pre- and post-workout products that are designed for our modern obesity medication users.”
