Drugs like semaglutide (Wegovy) and tirzepatide (Zepbound) are changing the game in obesity care. In clinical trials, they helped people lose as much as 15 to 20% of their body weight over the course of about a year -- and we've seen similar results in the real world since the drugs were approved for chronic weight management. That's great news considering the estimates that obesity will affect nearly half of the adult U.S. population by 2030. These drugs have the potential to significantly improve Americans' health -- but they're not without limitations.
People taking GLP-1s eventually tend to reach plateaus, points at which they can't seem to lose any more weight, even if they still carry excess fat. That shouldn't come as much of a surprise since plateaus commonly occur with all weight loss interventions, whether diets, surgery, or weight loss medications.
Plateaus aren't a problem of willpower -- they're intimately connected to brain chemistry and metabolism. Hunger hormones kick in to resist calorie restriction at the same time that a slower metabolism burns fewer calories.
Every treatment or behavior change eventually plateaus. Knowing that plateaus are inevitable, it's important to set patient expectations. Physicians should educate their patients at the outset of treatment that no intervention is a "cure-all" and that they'll still have to adopt a healthy diet and an active lifestyle to make lasting change. Should the patient reach a GLP-1 plateau before reaching their desired weight or target health indicators, the physician and patient should have a conversation about what other interventions might make sense.
Simply writing GLP-1 prescriptions isn't going to solve the obesity crisis, especially since the drugs' hefty price tags limit access. We need to approach obesity from all angles to help patients understand or break through plateaus when they happen.
Support Patients in Lifestyle Changes
Many people battling obesity have tried numerous fad diets without lasting success. However, few have received personalized support from registered dietitians and health coaches. If given the choice, some people may opt to work with a registered dietitian before turning to medications like GLP-1s.
Regardless of whether patients have previously worked with a registered dietitian, we should be offering them dietary support when taking GLP-1s. In fact, GLP-1s are only FDA-approved for weight loss when used as an adjunct to behavior modification. Dietitians can help patients handle side effects and prevent malnutrition while on the drugs, and provide medical nutrition therapy to help people lose weight in a healthy, sustainable way. That might look like prioritizing protein to help prevent muscle loss or suggesting certain eating times and nutrients (like increasing fiber intake) that can help people break through weight loss plateaus.
Health coaches can also support people with new exercise routines like strength training or jogging. Studies show that moderately exercising for 150 minutes per week when on a GLP-1 results in greater fat loss and weight loss maintenance than when taking the drugs alone.
Try Different Drug Combinations
There are many alternatives to GLP-1s that can work as anti-obesity medications, disrupting different parts of the brain. While GLP-1s stimulate insulin secretion and delay gastric emptying to reduce appetite, other drugs like phentermine (Lomaira) stimulate the release of norepinephrine to reduce appetite. Topiramate (Topamax), traditionally used to manage epilepsy and chronic migraines, also suppresses appetite and prolongs a feeling of fullness. And there are more drugs -- like metformin (Fortamet), bupropion/naltrexone (Contrave), and zonisamide (Zonegran) -- that all target different hormones and receptors to induce weight loss.
If a patient reaches a plateau on one drug and is still struggling to meet metabolic indicators of health or desired weight loss, switching to another drug that targets a different area of the brain can help. This makes it harder for the body to acclimate to one type of drug.
Treat Underlying Mental Health Conditions
Obesity and depression often go hand-in-hand. Data from a meta-analysis show that people with obesity have a 55% elevated risk of developing depression, while those with depression have a 58% higher risk of developing obesity. Other mental health conditions like anxiety and disordered eating can also contribute to obesity.
Depression is linked to a sedentary lifestyle and emotional eating that can make it harder to break through weight-loss plateaus. And while losing weight on GLP-1s may lift depression for some, it may worsen it for others. It's essential that we get to the root of mental health issues tied to obesity. Cognitive behavioral therapy (CBT) is designed to change harmful thought patterns, help provide structure, and determine priorities, increasing patients' sense of control and autonomy.
While GLP-1s can help with binge-eating or night-eating, they may also trigger other disordered eating behaviors. Just like we often require therapists to work with patients undergoing bariatric surgery and the transformation that comes after, it's important to offer mental health support for those undergoing their own transformations with GLP-1s. The last thing we want is to break through a plateau at the cost of trading obesity for anorexia or another life-threatening eating disorder.
Obesity Is a Chronic Condition
At the end of the day, we have to remember that obesity is a chronic condition. The American Medical Association has recognized it as a disease state with "multiple pathophysiological aspects" for over 10 years now. It shouldn't be surprising that many people will face a resistance to weight loss -- no matter the intervention.
Even if people reach a seemingly unbreakable plateau, that doesn't mean the GLP-1s aren't "working." We're now discovering that GLP-1s benefit heart and renal health too. The number on the scale doesn't tell the whole story. Just 5% to 10% weight loss can produce meaningful outcomes in overall health. It's important to make sure patients understand this from the outset.
While plateaus are an expected part of the journey with GLP-1s, we can navigate those challenges with proactive strategies and comprehensive approaches to ensure progress and patient feelings of success.
Fatima Cody Stanford, MD, MPH, MPA, MBA, is an internist, pediatrician, and obesity medicine physician scientist at Massachusetts General Hospital (MGH) and Harvard Medical School. She is the director of Equity for the Endocrine Division of Medicine for MGH, the director of Diversity for the Nutrition Obesity Research Center at Harvard, and the director of Anti-Racism Initiatives for the Neuroendocrine Unit. Richard Frank, MD, MHSA, is chief medical officer at Vida Health, a virtual care platform.
Disclosures
Stanford has served as a consultant or advisor to Novo Nordisk, Eli Lilly, Boehringer Ingelheim, Pfizer, Currax, Rhythm, Gelesis, Vida Health, Calibrate, GoodRx, Coral Health, Sweetch.