As the popularity of GLP-1 (Glucagon-Like Peptide-1) agonists. including semaglutide – branded as Wegovy or Ozempic, and tirzepatide (dual GIP/GLP-1 receptor agonist) – branded as Zepbound or Mounjaro, for the management of obesity, type 2 diabetes, and other metabolic conditions increases, so too does the need to assess the advantages and potential downsides of long-term use. While these medications can be very effective for weight control and diabetes support, questions around the optimal dietary approach in users remain. This article seeks to consider the nutritional implications of GLP-1 drugs as we await more specific, science-backed dietary guidelines. Additionally, we discuss other benefits and risks of these medications, and how to personalize care to individuals on these medications.
How it Works
GLP-1 agonists mimic the actions of the naturally occurring GLP-1 incretin hormone, released in response to food intake. They play a role in:
- Increasing insulin secretion: helping reduce blood glucose levels in individuals with impaired insulin sensitivity.
- Suppressing glucagon secretion: this helps prevent unnecessary glucose release by the liver.
- Delaying gastric emptying: slowing digestion, which helps to reduce hunger.
- Promoting satiety: by acting on areas of the brain related to appetite control.
GIP
GIP is an incretin hormone and stands for gastric inhibitory polypeptide (renamed: glucose‐dependent insulinotropic polypeptide). It is normally secreted from the intestine upon ingestion of glucose, fatty foods or nutrients to stimulate insulin secretion by pancreas.
One hypothesis is that chronic GIP receptor agonism desensitizes the GIP receptor, creating an antagonism, which ultimately leads to weight loss. This is a topic of further study, however, given that both agonism and antagonism have been observed to play a role in weight loss.
Benefits
Effective Weight Loss: Clinical trials have demonstrated that GLP-1 agonists can lead to significant weight loss, especially in individuals with obesity or overweight conditions. For example, a 2021 study on semaglutide showed an average weight loss of around 15% in obese individuals over 68 weeks on maximum dose of semaglutide, compared to a placebo group’s 2.4%. The 2022 tirzepatide study demonstrated an average body weight reduction of 20% in obese individuals over 72 weeks on maximum dose of tirzepatide. 1
Improved Blood Glucose Control: GLP-1 agonists can reduce HbA1c (a marker of average blood glucose levels over 3 months) by around 1% to 2%, which is comparable to or even exceeds other diabetes treatments. 2
Cardiovascular Benefits: Research has shown that some GLP-1 agonists, such as liraglutide and semaglutide, reduce major adverse cardiovascular events in people with type 2 diabetes. These events include heart attack, stroke and cardiovascular death. This protective effect could be attributed to weight loss, better blood sugar control, or even direct effects on heart function. 3
Reduced “Food Noise”: In our practice, one of the most consistent and profound effects we observe with these treatments is the dampening of “food noise.” Patients across the board report a significant reduction in the constant mental chatter around food—less overthinking about food choices, fewer cravings, and an overall shift in their relationship with eating. This effect alone can be transformative, fostering a more intuitive and less stressful approach to nourishment. The consistency of patient-reported experiences suggests a meaningful impact on appetite regulation and food-related behaviors.
Alcohol Consumption: Emerging research suggests GLP-1 agonists may also influence alcohol consumption, with preliminary findings indicating a potential reduction in binge drinking, alcohol cravings, and desire to drink among users. While the exact mechanisms are still being explored, researchers believe GLP-1’s may impact the brain’s reward pathways, which could have implications for alcohol use disorder. These early insights are promising, but more research is needed to fully understand this connection and how it might be applied in clinical practice. 4
Additionally, GLP-1 medications can lower tolerance to alcohol, which can result in feeling its effects more intensely than usual. It’s important to be aware of this potential side effect and make responsible decisions when drinking, such as consuming alcohol in moderation, staying hydrated, and monitoring how your body responds.
Anti-inflammatory Effects: Beyond appetite regulation, emerging research suggests that GLP-1 therapies may also contribute to lowering CRP (C-reactive protein), a key inflammatory marker. A reduction in CRP has been linked to a lower risk of heart disease, stroke, and metabolic disorders such as insulin resistance and type 2 diabetes. Additionally, lower CRP levels are associated with better outcomes in autoimmune and chronic inflammatory conditions, as well as improved overall longevity and long-term health. While the exact mechanism remains unclear, this reduction could be tied to weight loss, visceral fat reduction, improved glucose control, or potentially an independent anti-inflammatory effect. Studies, including those published in The Lancet, highlight GLP-1’s broader metabolic benefits, reinforcing its role not just in weight management but in systemic inflammation reduction. 5
As we continue to understand the full spectrum of GLP-1’s impact, these findings underscore its potential as a powerful tool in both metabolic and inflammatory health.
Reported Risks and Side Effects
Gastrointestinal Issues: These may include nausea, vomiting, bloating, diarrhea, constipation, and slowed gastric emptying, which can sometimes lead to discomfort or changes in appetite. Symptoms are often dose-dependent and may improve over time as the body adjusts to the medication. These symptoms tend to be heightened upon increase in dose and within the first two days of injection. In our practice, we counsel patients regarding such symptoms and provide strategies to help manage them. However, if any severe symptoms are experienced, such as significant upper abdominal pain with nausea and vomiting, we recommend urgent evaluation given the possibility of pancreatitis or other more acute conditions. 6
Gallbladder Issues: GLP-1 agonists have been associated with an increased risk of gallbladder disease, including gallstones (cholelithiasis) and gallbladder inflammation (cholecystitis). This may be related to rapid weight loss or changes in bile composition. Patients should be aware of potential symptoms such as persistent right upper abdominal pain, especially after eating, nausea, or jaundice. If these symptoms occur, prompt medical evaluation is needed. 7
Hypoglycemia (Low blood glucose) Risk: While GLP-1 agonists have a lower risk of causing hypoglycemia compared to other diabetes medications, the risk increases significantly when they are used in combination with insulin or sulfonylureas, which actively lower blood sugar. Symptoms of low blood sugar can include dizziness, sweating, shakiness, confusion, weakness, and, in severe cases, loss of consciousness or seizures. Patients should monitor for signs of hypoglycemia, especially if taking other glucose-lowering medications, and have a plan in place to quickly correct low blood sugar when needed (such as consuming glucose tablets or a fast-acting carbohydrate). Dose adjustments of insulin or sulfonylureas may be necessary to minimize this risk, and we encourage patients to discuss any concerns with their healthcare provider. 8
Thyroid Tumor Risk: GLP-1 agonists have been shown to cause dose- and duration-dependent thyroid C-cell tumors in rodents.9 While it is unclear if this risk applies to humans, caution is advised. These medications are strictly contraindicated in individuals with a personal or family history of medullary thyroid carcinoma (MTC) or Multiple Endocrine Neoplasia syndrome type 2 (MEN 2), a rare genetic disorder, causing certain endocrine tumours to develop. Patients should be fully informed of the potential risk and advised to seek immediate medical evaluation if they develop symptoms such as a lump in the neck, difficulty swallowing, persistent hoarseness, or trouble breathing. Routine monitoring for thyroid cancer is not recommended by guidelines, but any concerning symptoms should be taken seriously and promptly assessed by a healthcare provider. 10
Potential Impact on Metabolism and Muscle Mass: GLP-1 agonists, while effective for weight loss, contribute to lean muscle mass loss alongside fat reduction. Although not universally observed, studies suggest that individuals taking semaglutide and tirzepatide may experience a significant loss of lean muscle mass, along with fat mass (15-60% of weight loss).11 12 This raises concerns about potential long-term effects on metabolic health, strength, and physical function. Since maintaining muscle mass is essential for metabolic stability, mobility, and overall health, it is important for individuals on GLP-1 therapy to prioritize resistance training and adequate protein intake to help mitigate these effects. Regular monitoring of body composition, rather than just overall weight loss, may also be beneficial in ensuring a balanced and healthy weight reduction.13
Considerations and Questions for Long Term Use
While short-term benefits are clear, the effects of prolonged GLP-1 agonist therapy needs further study. Given the effects on human metabolism, long-term use raises questions about how these treatments may reshape metabolic function, beyond therapy duration.
Recent research suggests GLP-1 medications provide long-term cardiovascular and kidney benefits, even for individuals without type 2 diabetes. 14 However, concerns remain about potential side effects, including an increased risk of thyroid cancer. The FDA includes a warning about medullary thyroid carcinoma and advises against use in individuals with a family history of the disease or a family history of MEN 2 . The FDA has recently approved Ozempic to reduce the risk of kidney failure and cardiovascular events in diabetes patients with chronic kidney disease.
Public opinion remains divided, with about half of U.S. adults supporting GLP-1 medications for obesity treatment in adults but showing less support for adolescent use. Concerns persist about insurance coverage and the importance of maintaining lifestyle changes alongside medication.
Metabolic effects: Will GLP-1 agonists impact natural metabolic rhythms as a result of its role in altered digestive function, insulin, and appetite? We do not yet know if these interventions will disrupt the body’s endocrine-regulatory process over time. We see that the satiety response to GLP-1 agonists seems to wane with prolonged use.
What happens when medication is discontinued: Studies show most people regain some or all weight lost when stopping therapy, suggesting a life-long reliance to maintain results. After 1 year of cessation of semaglutide at maximum dose, people regained, ⅔ of the weight they lost.15 This raises questions about sustainability, accessibility, as well as cost.
Loss of muscle mass: Evidence suggests most individuals experience lean mass loss with these therapies. Loss of muscle can be detrimental to metabolism and aging, affecting strength, mobility, decreasing metabolic rate, increasing risk of insulin resistance, diabetes, cardiovascular health, and overall quality of life. 16
Risk of nutrient deficiencies: GLP-1 agonists significantly reduce appetite, gastrointestinal motility, and nutrient absorption, leading to reduced calorie and protein intake. They may potentially lead to deficiencies in vitamins and minerals like B12, iron, and calcium.17
Current Nutrition Guidelines: There is no standardized “GLP-1 diet plan” for individuals using these medications. However, a 2024 study published in Obesity recommends an evidence-based approach centered on a “healthy dietary pattern” that includes vegetables, fruits, whole grains, lean proteins, low-fat dairy, and healthy fats. Despite this guidance, there remains a notable gap in defined strategies to manage side effects and support the preservation of lean muscle mass and physical strength.18
The Need for Personalized Nutrition
Making changes to address chronic disease management and weight loss requires a multi-faceted and individual approach. Identifying personal barriers, socioeconomic factors, education, and self-efficacy to improve disease risk and weight loss are crucial to the long-term success and benefits these medications provide. Without a strong foundational lifestyle and defined habits, the long term improvements and post-therapy satisfaction may be diminished.
Dietary and Lifestyle Recommendations: Key Takeaways
Protein Intake: Adequate protein intake is critical for maintaining muscle mass during weight loss, especially for individuals on GLP-1 agonists, as appetite suppression effects may inadvertently lead to lower calorie and protein consumption. General guidelines for protein intake are 0.8 grams per kilogram of body weight per day for the average adult. However, for those on GLP-1 agonists, studies recommended increasing protein consumption to 1.2-2.0 grams per kilogram of body weight. Higher protein intake is associated with better preservation of lean muscle mass, improved satiety, and sustained resting metabolic rate. It is advised to work with a knowledgeable nutritionist or health coach who can help calculate individual protein needs and a specific diet plan. Protein sources such as low fat Greek Yogurt, eggs, chicken, turkey, fish, lentils, legumes, nuts and seeds are particularly useful here. 19
Meal Replacements: Meal replacement shakes can be an effective way to meet protein and calorie needs when appetite and desire for food is diminished. The best options for a meal replacement are high in protein with at least 20-30 grams per serving, low in added sugars (ideally less than 10 grams per serving), and fortified with essential vitamins and minerals to support overall nutrition. A trained health professional can help identify which options are best and if a protein powder recommendation is indicated. Shakes including grass fed whey isolate, organic pea protein, and pumpkin seed protein are clean options. It is important to use a reliable brand, given potential for protein powders to contain high levels of heavy metals.
Fiber: Emphasizing a variety of vegetables, low-glycemic fruits, lentils, legumes, whole grains, nuts, and seeds, can help improve motility and diversify the gut microbiome. GLP-1’s delay gastric emptying which can lead to constipation and bloating. The general recommendation for fiber is 25-40 grams daily.
The Role of Exercise in Avoiding Muscle Wasting: Regular exercise and adequate movement is crucial to prevent muscle loss and promote metabolic rate. A 2023 study published in Diabetes, Obesity, and Metabolism demonstrated that GLP-1 agonist users engaging in regular physical activity experienced better weight loss quality, retaining more muscle mass compared to those who did not exercise. Resistance exercises such as weight lifting, bodyweight squats, and pushups stimulate protein synthesis and counteract muscle breakdown while in a caloric deficit. Two – three, 30-45 minute sessions of resistance training per week, targeting all muscle groups is sufficient to stimulate muscle synthesis. Engaging in at least 150 minutes of moderate-intensity aerobic activity per week such as brisk walking, swimming, or cycling aims to complement resistance training by improving cardiovascular health. Yoga and stretching 2-3 times per week can enhance mobility and prevent injury.
Calories and Macronutrient Balance: While GLP-1 agonists reduce appetite, patients must ensure they consume sufficient calories and protein to fuel workouts and stimulate muscle synthesis and prevent fatigue. Undereating can lead to reduced exercise performance and increased risk of muscle wasting. 20 21
Getting the Right Support: As these medications become more popular for the treatment of obesity and diabetes, the integration of professional nutrition and health coaching guidance has emerged as a critical factor in optimizing outcomes and achieving sustained results. Professional guidance allows patients to adopt higher-protein diets and commit to regular physical activity, preventing muscle wasting. A study in the Journal of Nutrition demonstrated how patients were able to maintain weight loss and metabolic improvements 12-months post-therapy when engaged in regular nutrition coaching. These findings show the value of accountability and ongoing behavioral support when taking GLP-1 agonists, even after treatment has stopped. 22
Practical Tips:
- Work with your care team and a qualified nutritionist to help create personalized goals and dietary recommendations you feel confident following.
- Reach for high protein snacks like hard boiled eggs, roasted chickpeas, Greek yogurt, and high quality, minimally processed protein bars, powders/shakes.
- Hydrate! Approximately ½ body weight in ounces is the minimum recommendation. GLP-1’s can cause mild dehydration as a result of slower gastric emptying.
- Consider more frequent, smaller meals to address reduced appetite.
- Eat slowly and mindfully, and avoid meals too close to bedtime.
- Make workout goals attainable and fun!
At our practice, we offer comprehensive support for patients pursuing sustainable weight loss, improved metabolic health and longevity, including those using GLP-1 medications. Our personalized approach focuses on optimizing metabolic health, managing insulin resistance, and addressing key lifestyle factors for long-term success. Through tailored nutrition strategies and individualized fitness guidance, we empower patients to achieve balanced, lasting results. To learn more about how we can support your weight loss journey, contact us at 646.627.8000, fill out this form for a complimentary discovery call, or email Bridget@drbojana.com
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- https://www.sciencedirect.com/science/article/pii/S2161831322006810?via%3Dihub
- https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(24)00054-3/fulltex