GLP-1s Only Opening Act: Experts Unveil Diet-Exercise Guide

The weight loss seen with GLP-1 receptor agonists is only half the story. Long-term success hinges on integrating medication with individualized nutrition and physical activity counseling, a trio of experts remind clinicians in a new paper.

GLP-1 medications and dual receptor agonist medications are “very effective in terms of weight loss, achieving about 20% weight loss or more,” JoAnn Manson, MD, MPH, professor of medicine, Harvard Medical School and Brigham and Women’s Hospital, both in Boston, told Medscape Medical News.

However, the loss of muscle mass and lean body mass is also “quite common, sometimes accounting for 25% or more of the total weight loss.” Lifestyle factors are “crucial” to optimize outcomes for patients on GLP-1 medications, Manson said.

She and her coauthors offered advice on integrating diet and physical activity and managing potential side effects in patients with obesity starting a GLP-1 medication in a brief two-page “Clinical Insights” article in JAMA Internal Medicine. There is also companion “Patient Page.”

Monitor Weight Loss 

Clinicians should track weight monthly during GLP-1 dose escalation and at least quarterly thereafter, intervening if patients lose too little or too much weight, the authors advised.

For those with < 5% weight loss after 12-16 weeks, options include continuing standard dose escalation and documenting progress, given that standard titration periods (at least 17 weeks) may not work for all individuals; checking for missed doses and adjust dose titration as needed to maximize adherence; or switching to an alternative GLP-1 drug if the maximum tolerated dose is not effective, they said.

It’s also important to monitor for excessive weight loss, the authors said. Indications that weight loss may be excessive or harming overall health include a BMI < 18.5, anorexia (consuming < 800 calories/d), or very low protein intake.

In a patient with excessive weight loss, it’s important to rule out secondary causes such as eating or endocrine disorders or malignant tumors, assess for correlated harms including nutrient deficiencies and hormonal imbalances, assess psychological function with referrals to specialists as needed, and consider dose reduction or stopping the medication temporarily, the author advised.

Assess Diet, Manage Nutrient Intake 

If available, patients should see a registered dietitian initially, with follow-up visits every 2-3 months during dose escalation. If this is not feasible, clinicians can administer the Rapid Eating Assessment for Participants-Shortened, a brief nutritional assessment tool.

The authors emphasized that nutrient quality is more important than rigid calorie counting. However, patients may also benefit from periodic tracking of their food and fluid intake through smartphone applications, manual food logs or taking photos of their food to help guide dietary adjustments. For patients comfortable with tracking their calories, target calorie ranges should be individualized based on weight goals and activity level.

To minimize muscle loss, patients should be advised to maintain adequate protein intake of 60-75 g/d (1.0-1.5 g/kg; > 1.5 g/kg for older or post-bariatric surgery patients) and engage in structured physical activity (aerobic and strength training).

To maintain energy balance, smaller, nutrient-dense meals rather than calorie restriction is advised. Whole grains for satiety and sustained energy and healthy fats to support fat-soluble vitamin absorption and reduce cholestasis are recommended.

Manson noted that “gastrointestinal symptoms — such as nausea, constipation, and reflux — can limit the use of these medications, lead to drug discontinuation, and subsequently results in weight regain.” 

To help ward off constipation, patients should be advised to increase fiber intake and take in more than 2-3 L of fluid a day and use over-the-counter laxatives if needed. For nausea, they should avoid fried foods and carbonated drinks. For reflux, eating smaller portions, not lying down for 2-3 hours after meals and limiting high-fat and irritating spices may help.

Because appetite suppression induced by GLP-1 medications can unmask hidden micronutrient deficiencies, clinicians could consider assessment of vitamin D, iron, B-vitamins, and other micronutrients and add a multivitamin when intake is chronically low, the authors said.

Physical Activity: Start Slow and Add-On

The authors recommend a three-step approach to counseling patients on physical activity.

First, introduce regular movement gradually and work up to 150 minutes of moderate (or 75 min of vigorous) activity weekly. Second, incorporate resistance training, aiming for 60-90 min/wk. Third, maintain 30-60 minutes per day of aerobic exercise combined with resistance training two to three times per week for optimal long-term weight and metabolic outcomes.

Balance and mobility training for older adults can be especially helpful, the author said. Clinicians may also consider assessing muscle strength and function, such as the grip strength or 6-minute walk test, the authors said.

Weight Regain 

Patients who discontinue GLP-1 therapy may regain weight and this should be discussed with patients at the start of treatment, the authors said.

Specifically, in randomized controlled trials, weight rebound of roughly 7%-12% has been observed within 1 year of stopping GLP-1 therapy and that lifestyle habits put in place early will be the main defense if dose reductions or discontinuation are attempted.

The authors noted that all patients will reach a weight-loss plateau, but weight maintenance protocols for GLP-1 drugs have yet to be established. “Clinicians should base treatment decisions on the premise that obesity is a chronic condition typically requiring long-term management, similar to hypertension,” they advised.

When a decision to taper the medication is made, options include reducing the dose or frequency of injections or tapering off treatment completely with progressively less monitoring (weekly to biweekly, followed by monthly, then quarterly) over at least 20 weeks.

“Clinicians should continue to assess weight, metabolic health, diet and activity levels, appetite, sleep patterns, mood changes, and muscle strength. Medication reinitiation or dose increase should be considered if weight regain exceeds 5%,” they advised.

Manson told Medscape Medical News she hopes this information will be a “good resource that will result in better care for patients on GLP-1 medications and better outcomes.”

This research had no commercial funding. The authors had no relevant disclosures.