Are Patients On GLP-1s Getting the Right Nutrients?

As the use of glucagon-like peptide 1 receptor agonists (GLP-1 RAs) continues to exponentially expand obesity treatment, concerns have arisen regarding their impact on nutrition in people who take them.

While the medications’ dampening effects on appetite result in an average weight reduction ≥ 15%, they also pose a risk for malnutrition.

“It’s important to eat a balanced diet when taking these medications,” Deena Adimoolam, MD, an endocrinologist based in New York City and a member of the national advisory committees for the Endocrine Society and the American Diabetes Association, told Medscape Medical News. “If someone’s diet is minimal, it’s important they’re keeping up with their need for macronutrients — protein, fat, carbohydrates — as well as micronutrients — vitamins and minerals.”

The decreased caloric intake resulting from the use of GLP-1 RAs makes it essential for patients to consume nutrient-dense foods. Clinicians can help patients achieve a healthy diet by anticipating nutrition problems, advising them on recommended target ranges of nutrient intake, and referring them for appropriate counseling.

Where to Begin

The task begins with “setting the right expectations before the patient starts treatment,” said Scott Isaacs, MD, president-elect of the American Association of Clinical Endocrinology.

To that end, it’s important to explain to patients how the medications affect appetite and how to adapt. GLP-1 RAs don’t completely turn off the appetite, and the effect at the beginning will likely be very mild, Isaacs told Medscape Medical News.

Some patients don’t notice a change for 2-3 months, although others see an effect sooner.

“Typically, people will notice that the main impact is on satiation, meaning they’ll fill up more quickly,” said Isaacs, who is an adjunct associate professor at Emory University School of Medicine, Atlanta. “It’s important to tell them to stop eating when they feel full because eating when full can increase the side effects, such as nausea, vomiting, diarrhea, and constipation.”

A review article, written by lead author Jaime Almandoz, MD, University of Texas Southwestern Medical Center, Dallas, in Obesity offers a “5 A’s model” as a guide on how to begin discussing overweight or obesity with patients. This involves asking for permission to discuss weight and asking about food and vitamin/supplement intake; assessing the patient’s medical history and root causes of obesity, and conducting a physical examination; advising the patient regarding treatment options and reasonable expectations; agreeing on treatment and lifestyle goals; and assisting the patient to address challenges, referring them as needed to for additional support (eg, a dietitian), as well as arranging for follow-up.

Impact of GLP-1 RAs on Food Preferences

Besides reducing hunger and increasing satiety, GLP-1 RAs may affect food preferences, according to a research review published in the International Journal of Obesity. It cites a 2014 study that found that people taking GLP-1 RAs displayed decreased neuronal responses to images of food measured by functional magnetic resonance imaging in the areas of brain associated with appetite and reward. This might affect taste preferences and food intake.

Additionally, a 2023 study suggested that during the weight-loss phase of treatment (as opposed to the maintenance phase), patients may experience reduced cravings for dairy and starchy food, less desire to eat salty or spicy foods, and less difficulty controlling eating and resisting cravings.

“Altered food preferences, decreased food cravings, and reduced food intake may contribute to long-term weight loss,” according to the research review. Tailored treatments focusing on the weight maintenance phase are needed, the authors wrote.

Are Patients Vulnerable to Malnutrition?

A recent review found that total caloric intake was reduced by 16%-39% in patients taking a GLP-1 RA or dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 RA, but few studies evaluated the composition of these patients’ diets. Research that examines the qualitative changes in macronutrient and micronutrient intake of patients on these medications is needed, the authors wrote.

They outlined several nutritional concerns, including whether GLP-1 RA or GIP/ GLP-1 RA use could result in protein intake insufficient for maintaining muscle strength, mass, and function or in inadequate dietary quality (ie, poor intake of micronutrients, fiber, and fluid).

“Although we don’t necessarily see ‘malnutrition’ in our practice, we do see patients who lose too much weight after months and months of treatment, patients who aren’t hungry and don’t eat all day and have one big meal at the end of the day because they don’t feel like eating, and people who continue to eat unhealthy foods,” Isaacs said.

Some patients, however, have medical histories placing them at a greater risk for malnutrition. “Identification of these individuals may help prevent more serious nutritional and medical complications that might occur with decreased food intake associated with AOMs [anti-obesity medications],” Almandoz and colleagues noted in their review.

What Should Patients Eat?

Nutritional needs vary based on the patient’s age, sex, body weight, physical activity, and other factors, Almandoz and colleagues wrote. For this reason, energy intake during weight loss should be “personalized,” they added.

The authors also recommended specific sources of the various dietary components and noted red flags signaling potential deficiencies (Table).

Nutritional needs vary based on the degree of appetite suppression in the patient, Adimoolam said. “I recommend at least two servings of fruits and vegetables daily, and drinking plenty of water throughout the day,” she added.

Protein in particular is a “key macronutrient,” and insufficient intake can lead to a variety of adverse effects, including sarcopenia — which is already a concern in individuals being treated with GLP-1 RAs. Meal replacement products (eg, shakes or bars) can supplement diets to help meet protein needs, especially if appetite is significantly reduced.

“There are definitely concerns for sarcopenia, so we have our patients taking these drugs try to eat healthy lean proteins – 100 g/d — and exercise,” Isaacs said. Exercise, including resistance training, not only improves muscle mass but also potentiates the effects of the GLP-1 RAs in patients with obesity and type 2 diabetes.

Adequate hydration is essential for patients taking GLP-1 RAs. “One of the commonly described side effects is fatigue, but there’s no biological reason why these medications should cause fatigue. My opinion is that these patients are dehydrated, and that may be causing the fatigue,” Isaacs said.

Some patients taking GLP-1 RAs lose interest in food. Isaacs regarded this as an “adverse reaction to the medication, which necessitates either stopping it altogether, changing the dose, or adjusting the diet.” There are “many different solutions, and one size doesn’t fit all,” he said.

Dietary and Behavioral Counseling

The drugs don’t necessarily motivate a person to eat healthier food, only to eat less food, Isaacs noted.

“The person might be eating low-volume but high-calorie food, such as bag of chips or a cookie instead of an apple,” Isaacs said. Patients who are losing weight “may not realize that weight loss isn’t the only important outcome. Because they’re losing weight, they think it’s okay to eat junk food.”

Patients need education and guidance about how to eat while on these medications. Most patients find counseling about meal planning helpful, he said.

Isaacs gives nutritional guidance to his patients when he prescribes a weight loss medication. “But most physicians don’t have time to offer that type of specific counseling on an ongoing basis,” he said. Isaacs refers patients requiring more detailed and long-term guidance to a dietician.

Patients with monotonous diets of poor quality are at increased risk for nutrition deficiencies, and counseling by a registered dietitian could help improve their dietary quality.

Registered dieticians can develop a multifaceted approach not only focusing on medication management but also on customizing the patient’s diet, assisting with lifestyle adjustments, and addressing the mental health issues surrounding obesity and its management.

People seeking obesity treatment often have psychiatric conditions, psychological distress, or disordered eating patterns, and q uestions and concerns have emerged about how GLP-1 RA use might affect existing mental health problems. For example, if the medication suppresses the feeling of gratification a person once got from eating high-energy dense foods, that individual may “seek rewards or pleasure elsewhere, and possibly from unhealthy sources.”

Psychological issues also may emerge as a result of weight loss, so it’s helpful to take a multidisciplinary approach that includes mental health practitioners to support patients who are being treated with GLP-1 RAs. Patients taking these agents should be monitored for the emergence or worsening of psychiatric conditions, such as depression and suicidal ideation.

Achieving significant weight loss may lead to “unexpected changes” in the dynamics of patients’ relationship with others, “which can be distressing.” Clinicians should be “sensitive to patients’ social and emotional needs” and provide support or refer patients for help with coping strategies.

GLP-1 RAs have enormous potential to improve health outcomes in patients with obesity. Careful patient selection, close monitoring, and support for patients with nutrition and other lifestyle issues can increase the chances that these agents will fulfill their potential.

Isaacs declared no relevant financial relationships.

Batya Swift Yasgur, MA, LSW is a freelance writer with a counseling practice in Teaneck, New Jersey. She is a regular contributor to numerous medical publications, including Medscape Medical News and WebMD, and is the author of several consumer-oriented health books, as well as Behind the Burqa: Our Lives in Afghanistan and How We Escaped to Freedom (the memoir of two brave Afghan sisters who told their story).