Are the GLP-1 Agonists "Forever Drugs?" It's an Open Question, According to Jonathan Bonnet, MD, MPH

The question of whether persistent use of GLP-1 receptor agonists (GLP-1s) is required to maintain significant weight loss is a matter of concern for both patients and health care professionals and a topic of ongoing research.

In a recent interview with Patient Care,© Jonathan Bonnet, MD, MPH, an obesity medicine specialist and coauthor of a recently published joint advisory on lifestyle interventions to maintain adequate nutrition during treatment with the antiobesity medications said "at this point, the best evidence that exists out there suggests that [GLP-1 medications] probably are" needed chronically. But there is a tremendous amount of research yet to be done, he added. Bonnet feels the most important area to focus on now is how to optimize nutrition, physical activity and other lifestyle factors during weight loss therapy so that if and when an individual transitions off a GLP-1, the potential for continued success is optimal.

The short video above is part of Patient Care's longer conversation with Bonnet about the joint advisory, Nutritional priorities to support GLP-1 therapy for obesity: A joint Advisory from the American College of Lifestyle Medicine, the American Society for Nutrition, the Obesity Medicine Association, and The Obesity Society. The collaboration is the result of the many issues emerging as GLP-1s are more widely prescribed in the clinical setting, including protein and other nutritional deficiencies and loss of lean muscle mass along with fat mass.

The following transcript has been lightly edited for style and flow.

Patient Care: Where do you see the most important needs for research right now on integrating medical and nutritional management of overweight and obesity, particularly for maintaining weight-loss long term?

Jonathan Bonnet, MD, MPH: Certainly the big question with the GLP-1s is, are these forever drugs? At this point, the best evidence we have suggests they probably are. There are plenty of ideas and strategies for how we might transition people off them—alternate dosing, lower doses of different medications to reduce cost—but there’s no significant, robust data showing that patients who lose weight on GLP-1s can transition to another approach, whether that’s a nutrition plan, lifestyle program, or something else, and maintain all the weight loss. I’m certain those studies are underway, but right now, we don’t have that data.

For me, some clear questions are: How do you optimize nutrition while patients are on these medications? For example, what’s the ideal protein target? There are lots of suggestions and recommendations. In our paper, we included that if you’re not adjusting for body weight, it’s probably 0.8 grams per kilogram per day. If you are adjusting for body weight, it’s likely in the range of 1.2–1.6 grams per kilogram of adjusted body weight. But what’s the actual number? Those are pretty big ranges.

We also need to know the optimal intake of other nutrients that might be important during weight loss, and how these needs vary by individual. And long term, how do you provide good nutrition support to help patients potentially transition off these drugs? What would that diet look like? What would need to be in place for people to come off them successfully without significant weight regain?

Those are the areas that would be most exciting and important—how to use these medications as tools, and then, if possible, transition patients back to a more “normal” physiological state where they can maintain a healthy weight.

Jonathan Bonnet, MD, MPH, is the program director of medical weight loss at the Clinical Resource Hub Weight Management Center at Palo Alto Veteran's Affairs in Palo Alto, California. He is also an associate professor (affiliate) at Stanford University School of Medicine, and serves on the board of the American Board of Lifestyle Medicine. Bonnet is board-certified in family, sports, obesity, and lifestyle medicine.

For more from our conversation with Bonnet, see:

• GLP-1 Medications Need a Permanent Place in Primary Care, Says Obesity Medicine Specialist
• Ready to Prescribe a GLP-1 Medication? Please Dive Deep Into the Patient's History First, Advises John Bonnet, MD,
• Beyond Nutritional Deficiencies: Managing GLP-1 Side Effects With Lifestyle Interventions
• Why 4 Medical Societies Issued a Joint Advisory on Nutrition and GLP-1 Therapy for Obesity