M&D Clinical Corner: GLP-1 Agonist Drugs

The Clinical Corner is a monthly feature that highlights a variety of important pharmacist topics that is written by Dr. Jesica Mills, PharmD, ND, MBA, RPh, BCES, BCLS, BCNP.

• How they work
• Why the Shortage?
• Compounded Versions – Legality?
• Results
• Side Effects and Prevention
• Lifestyle factors that affect GLP-1
• Resources for Patients

How they work

• GLP-1 (Glucagon-Like Peptide-1) is a gut hormone that regulates blood sugar by increasing insulin and decreasing glucagon.
• GLP-1 agonists mimic this function, aiding in blood sugar control and weight loss by boosting insulin and slowing gastric emptying.
• They also offer benefits like improved cell survival, reduced oxidative stress, and ehanced cardiovascular health (Drucker, 2016; Beiroa et al., 2014).

Why the Shortage?

• A shortage of GLP-1 agonists in the US stems from disruptions in the supply chain.
• Surging demand driven by social media and rising type 2 diabetes rates, and regulatory and patent issues restricting competition (Sisley, 2014).

Compounded Versions – Legality?

• Due to the shortage, compounded semaglutide or tirzepatide serve as substitutes for FDA-approved options like Ozempic and Mounjaro in diabetes care.
• While offering personalized treatment, these versions pose risks such as potency fluctuations.
• Patients should weigh benefits and risks with their healthcare provider.
• The FDA investigates counterfeit Ozempic and encourages reporting.

How much weight loss is expected?

• Ozempic claims an average weight loss of 9-14 pounds, although it is not approved for weight loss (Jun, 2019).
• For compounded semaglutide and Wegovy, the average weight loss to expect is around 35 pounds or 15% of their body weight.
• For Mounjaro, the weight you expect to lose in 12 months is 20-25% of your body weight.
• 40% of weight loss is from lean body mass.
• Rapid loss of lean body mass can lead to weakness, fatigue, decreased physical performance, and compromised immune function.
• Continued loss of lean body mass can contribute to sarcopenia, a condition characterized by progressive muscle loss and functional decline, which can increase the risk of falls, fractures, and loss of independence in older adults.
• Decreased muscle mass is associated with insulin resistance, metabolic syndrome, and cardiovascular complications, highlighting the importance of preserving lean body mass for overall health and longevity.

How to preserve lean body mass while taking GLP-1 agonists

• Incorporate resistance training: Perform resistance exercises targeting major muscle groups (squats, lunges, deadlifts, chest presses) at least 2-3 times per week.
• Optimize protein intake: Consume 0.7-1 gram of protein per pound of lean body mass from sources like lean meats, poultry, fish, eggs, and plant-based options. Distribute intake evenly throughout the day.
• Monitor calorie intake: Avoid excessive caloric restriction to prevent muscle loss. Work with a healthcare provider or dietitian to create a balanced meal plan that supports metabolism and preserves lean body mass.
• Stay active: Include regular physical activity such as walking, cycling, swimming, or yoga to maintain muscle function and metabolic health.
• Monitor progress and adjust: Track body composition and physical performance. If muscle loss or metabolic changes occur, consult your healthcare provider to adjust your treatment, diet, or exercise routine. Consider DEXA or 3D body scans for assessment.

What side effects to expect and how to mitigate or prevent them

• Gastrointestinal disturbances: Common side effects like nausea, vomiting, diarrhea, and abdominal discomfort often occur initially but may improve over time.
• Dietary adjustments: Eat smaller, frequent meals, avoid high-fat or spicy foods, include fiber-rich foods, and stay hydrated.
• Probiotics: Consider probiotics or probiotic-rich foods to support gut health.
• Hypoglycemia: While GLP-1 agonists alone rarely cause low blood sugar, combining them with insulin or sulfonylureas increases this risk.
• Blood sugar monitoring: Regularly check blood glucose levels and adjust medications as needed, possibly using continuous glucose monitors (CGMs).
• Carbohydrate intake: Maintain balanced carbohydrate intake and carry fast-acting carbs for emergencies.
• Injection-site reactions: Manage redness, swelling, itching, or pain with proper injection techniques, rotating sites, and using new needles.
• Topical treatments: Use over-the-counter creams with corticosteroids or antihistamines for injection-site discomfort.
• Weight loss: Monitor for rapid or excessive weight loss to avoid malnutrition and muscle loss.
• Nutritional support: Work with a dietitian to ensure balanced nutrition, considering protein supplements if needed.
• Strength training: Engage in resistance training 2-3 times a week to maintain or build muscle mass.
• Pancreatitis: Rare but serious risk; watch for severe abdominal pain, nausea, and vomiting.
• Limit alcohol: Reduce or avoid alcohol to lower pancreatitis risk.
• Hydration: Drink plenty of water, avoiding sugary drinks, to prevent dehydration and reduce pancreatitis risk.
• C-Cell Thyroid Tumors: Certain GLP-1 receptor agonists come with a boxed warning about potential medullary thyroid carcinoma (MTC) based on animal studies. While it’s uncertain if this risk translates to humans, healthcare providers should weigh benefits against risks, especially for patients with thyroid cancer history. Monitoring for thyroid abnormalities may be advised during GLP-1 agonist therapy.
• Mental Health and Other Side Effects: Anxiety, Depression, Cognitive Impairment, and Suicidal Ideation are documented side effects of GLP-1 agonists. As of January 2024, the FDA is investigating these drugs for suicidal ideation, hair loss, intestinal blockages, and aspiration. Warnings include changes in vision, kidney failure, gallbladder problems, gastroparesis, and drug interactions due to delayed gastric emptying.

Lifestyle factors that affect GLP-1

• Cannabis Use: Cannabis may lower GLP-1 levels, with acute use possibly increasing secretion temporarily and chronic use potentially desensitizing receptors.
• Diet: A diet rich in fiber, protein, and healthy fats stimulates GLP-1 release. Regular, balanced meals help maintain stable GLP-1 levels.
• Gut Microbiome: Specific gut bacteria like Akkermansia muciniphila and Bifidobacterium enhance GLP-1 production. Imbalances disrupt GLP-1 regulation, contributing to metabolic dysfunction.
• Physical Activity: Regular exercise, especially aerobic or resistance training, boosts GLP-1 secretion and improves metabolic health.
• Sleep: Adequate sleep duration and quality support GLP-1 regulation. Aim for 7-9 hours of quality sleep per night.
• Stress: Chronic stress suppresses GLP-1 secretion. Incorporate stress-reduction techniques like mindfulness or yoga into daily routines.

Recommendations for Patients Unable to Access GLP-1 Agonist Medications:

• Diet: Adopt a low-glycemic, high-fiber diet. Consider intermittent fasting.
• Exercise: Engage in regular physical activity, including both aerobic and resistance training.
• Stress Management: Practice stress-reduction techniques.
• Sleep: Prioritize quality sleep.
• Supplements: Consider probiotics, prebiotics, omega-3 fatty acids, or Calocurb for additional support.
• Medications:
  • DPP-4 Inhibitors: Consider medications such as sitagliptin, saxagliptin, linagliptin, or alogliptin, which inhibit the degradation of endogenous GLP-1, leading to increased circulating levels and improved glycemic control.
  • SGLT-2 Inhibitors: Explore the use of sodium-glucose co-transporter 2 (SGLT-2) inhibitors such as canagliflozin, dapagliflozin, or empagliflozin, which indirectly affect GLP-1 levels by promoting glucose excretion in the urine and improving insulin sensitivity.
  • Acarbose: Consider the use of acarbose, an alpha-glucosidase inhibitor, which delays carbohydrate absorption in the gut, resulting in more gradual glucose release and potentially enhancing GLP-1 secretion.

Patient Assistance Programs and Education from Manufacturers

• Remember the patient-assistance programs and education offered by medication manufacturers.
• These resources encompass dietary guides, savings cards, and access to health coaches.
  • Ozempic: https://www.ozempic.com/savings-and-resources
  • Mounjaro: https://mounjaro.lilly.com/diabetes-lifestyle
  • Wegovy: https://www.wegovy.com/tools-and-resources/tips-for-getting-started.html

References:

Drucker, D. J. (2016). The cardiovascular biology of glucagon-like peptide-1. Cell Metabolism, 24(1), 15-30. https://doi.org/10.1016/j.cmet.2016.06.009

Beiroa, D., Imbernón, M., Gallego, R., Senra, A., Herranz, D., Villarroya, F., … & Nogueiras, R. (2014). Glp-1 agonism stimulates brown adipose tissue thermogenesis and browning through hypothalamic ampk. Diabetes, 63(10), 3346-3358. https://doi.org/10.2337/db14-0302

Sisley, S., Gutiérrez-Aguilar, R., Scott, M. M., D’Alessio, D. A., Sandoval, D. A., & Seeley, R. J. (2014). Neuronal glp1r mediates liraglutide’s anorectic but not glucose-lowering effect. Journal of Clinical Investigation, 124(6), 2456-2463. https://doi.org/10.1172/jci72434

Sellers, S. and Utian, W. H. (2012). Pharmacy compounding primer for physicians. Drugs, 72(16), 2043-2050. https://doi.org/10.2165/11640850-000000000-00000

Jun, J. K. (2019). Focus on new diabetes treatment options with cardiovascular benefits. Journal of Contemporary Pharmacy Practice, 66(3), 34-40. https://doi.org/10.37901/jcphp18-00029

Dirks, M. L., Wall, B. T., & Loon, L. J. C. v. (2018). Interventional strategies to combat muscle disuse atrophy in humans: focus on neuromuscular electrical stimulation and dietary protein. Journal of Applied Physiology, 125(3), 850-861. https://doi.org/10.1152/japplphysiol.00985.2016