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GLP-1 Weight Loss Medications: What You Need to Know.

I’m confident you’ve heard about semaglutide (Ozempic, Wegovy, Rybelsus) or tirzepatide (Mounjaro, Zepbound) from a friend, a podcast, or your social feed by now. The before-and-after photos are quite dramatic. Perhaps you’ve wondered, “Is this my answer?” The popularity of these drugs has skyrocketed, and it’s easy to see why. They promise dramatic weight loss results and other health benefits, and many places offer them at a discounted price online with little medical oversight once prescribed. But here’s the catch: these medications are not benign.

I am a fan and prescriber of these medications. However, I make sure to have lengthy discussions with my patients, so they can make informed decisions about starting this class of medication. Many people getting them online do not receive that same level of attention to detail. So today, I want to talk about what these medications do, who can and cannot be on them, and all the things you need to know to have a healthy weight loss journey.

What are GLP-1 Medications?

GLP-1 stands for glucagon-like peptide 1, which is a hormone secreted from intestinal cells in response to eating glucose and fat. It stimulates insulin secretion, suppresses glucagon release, slows gastric emptying, promotes satiety, and reduces food intake, all of which contribute to postprandial glucose regulation and appetite control.1,2 Semaglutides and tirzepatide are known as GLP-1 agonists, which means they mimic the GLP-1 hormone our body naturally makes. They were originally developed to treat type 2 diabetes and later approved for obesity treatment. And yes, they work. The figure below offers a visual of the process.

Who Should (and Should Not) Consider a GLP-1?

While these medications to work, they have different United States Food and Drug Administration (FDA) indications.

Medication

Indication

Semaglutide

Ozempic (injectable)

Approved as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus, and to reduce the risk of major adverse cardiovascular events in adults with type 2 diabetes and established cardiovascular disease.3

Wegovy (injectable)

Approved for chronic weight management in adults with obesity (BMI ≥30 kg/m²) or overweight (BMI ≥27 kg/m²) with at least one weight-related comorbidity*, as an adjunct to a reduced-calorie diet and increased physical activity.4

Rybelsus (oral)

Approved for glycemic control in adults with type 2 diabetes mellitus, as an adjunct to diet and exercise.5

Tirzepatide

Mounjaro (injectable)

Approved as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.6-8

Zepbound (injectable)

Approved for chronic weight management in adults with obesity or overweight (with at least one weight-related comorbid condition*), as an adjunct to a reduced-calorie diet and increased physical activity. In 2025, tirzepatide also received FDA approval for the treatment of moderate to severe obstructive sleep apnea in adults with obesity.3,9

* High blood pressure, high cholesterol, or type 2 diabetes

 

It’s also important to note who should avoid these medications as well. People with a personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2 (MEN2), or those with a serious allergic reaction to these drugs should not use them.9-13 These medications are also contraindicated in patients with significant gastroparesis, recurrent ileus, or bowel obstruction.9,14-18 Caution is advised in those with a history of pancreatitis or current gallbladder disease, as the medications can worsen both, as well as in those with diabetic retinopathy or kidney disease.15,18-20 GLP-1 agonists should also be avoided in pregnancy and breastfeeding due to the potential for birth defects observed in animal studies and lack of safety information in humans.14,16

While there are clear indications for the medications, there is a very long list of patients who should not be on them, which is why a thorough medical evaluation matters before starting.

Baseline Testing Before You Start

While it is not written in stone that baseline testing is required before starting these medications, I want this data. This consists of getting vital signs, a body composition scan in my office, and blood work, and I have good reasons for all of this. First, I want to evaluate for the presence of any condition that would prohibit or warrant caution with the use of these medications. Next, I want to look for the presence of a secondary condition that would help get the medications covered by a patient’s drug plan. In my experience thus far, no insurance plans will cover the medications for obesity alone no matter how high the BMI, but they often will if either type 2 diabetes, high cholesterol, high blood pressure and/or sleep apnea are present. Lastly, I want to track fat loss versus skeletal muscle mass loss. If patients are not on a proper nutrition and exercise plan, a lot of the weight loss is also from skeletal muscle loss which is a problem. This step is often skipped with online purchases of the medications. That is basically flying blind, in my opinion.

Lifestyle Modifications Still Matter

Nutrition and Caloric Intake

Most people do not know the basics of nutrition, such as optimal caloric intake, nutrition requirements, and macronutrients. The standard American diet consists of high-calorie, nutrient-poor, processed foods (see blog post on processed foods). GLP-1 agonists help reduce the overall intake of these foods, but if patients do not learn to transition their diet to one that incorporates more nutrient-dense, lower-calorie foods, all of the weight will return once the medications are discontinued. Additionally, patients must be on high-protein diets while taking the medications, or they risk losing significant skeletal muscle mass. Nutrition education and coaching is essential for achieving long-term goals.

Exercise

I’ve said it before, and I’ll say it again: I do not like to exercise. I am always finding ways to motivate myself, but the fact is, if we don’t use it, we will lose it. We also lose out on a major way to influence our metabolism. That’s especially true while on these medications. Caloric restriction will lead to some amount of skeletal muscle mass loss no matter what.21 When you exercise, you can reduce the amount of skeletal muscle mass loss22,23 which is a more favorable long term goal (see sarcopenia post for more information). Exercise must be a central part of GLP-1 therapy, including both cardiovascular and resistance training. Having a structured program not only helps the body preserve skeletal muscle mass but also helps develop the habit of exercising, which is one of the most powerful tools we possess against the hallmarks of aging and for overall health.

Sleep

Every single one of my patients fills out a detailed sleep intake when we first meet. This provides me with the information I need to help optimize sleep for each of them. Sometimes we unmask undiagnosed sleep apnea. Sometimes we find areas to improve sleep hygiene. Sometimes we determine the patient may benefit from a vitamin supplement to help with sleep. If you don’t solve your sleep issues, then you will be too fatigued to exercise. If you don’t exercise, you will have poor body composition and just gain all the weight back in the long term.

Stress and Mindfulness

I have so many patients who emotionally eat or stress eat. They have constant food noise. When they’re on the medications, the food noise disappears. But if we don’t address the underlying issues, it all comes back when the medication is stopped. Teaching mindfulness to this specific group of patients provides them with the skill to determine whether they’re actually hungry, experiencing food noise, or simply stressed. It also gives them tools to address each of these scenarios.

Substances

So many of my patients do not realize how many calories they consume through alcohol. Educating patients about alcohol’s caloric content helps keep the weight off. Some of my patients rely on marijuana for sleep, and many of them feel too fatigued to exercise and binge eat while using it. If we don’t address these issues, we’re far less likely going to reach long-term goals.

Social connections

I also have patients who are lonely or lack a support system. Every weight loss and health journey should include support for those who don’t have one. Creating a buddy system or accountability partner enhances long-term success.24,25

All of these lifestyle pillars are connected and work synergistically. While the medications accelerate the process, lifestyle modifications remain paramount for long-term success. And yes, it is true that some people cannot come off these medications and need them to treat obesity as a chronic condition. But many patients can come off them and stay off them when lifestyle modifications are part of the prescription.

What are the Side Effects and Adverse Consequences of GLP-1 Agonists?

We’ve discussed a lot of the benefits of these medications, but every new medication decision requires a thorough discussion of the adverse effects as well. The good news is the most common adverse consequences are gastrointestinal side effects (nausea, vomiting, diarrhea, constipation, and abdominal pain) that are typically dose-dependent, temporary, and often improve with continued therapy or slow dose escalation.6,15,26-29 Nausea occurs up in up to 44% of patients on semaglutide and 28% for those on higher doses of tirzepatide.26 Other notable adverse effects include gallbladder disease, pancreatitis, hypoglycemia, worsening of diabetic retinopathy, gastroesophageal reflux disease, acute kidney injury, and hypersensitivity reactions.6,15,26-30 The GI symptoms are the most common cause of discontinuation of therapy.26

Cost, Access, and the Problem with Compounding

Cost is one of the biggest barriers. Insurance coverage is hit-or-miss, and the retail price can be more than a thousand dollars a month. Some people turn to compounded semaglutide or tirzepatide from online pharmacies because it’s cheaper, but this comes with risks.

The FDA has issued warnings about compounding pharmacies selling incorrect formulations, contaminated products, or semaglutide “salts” that aren’t the same as the FDA-approved drug. If you’re not getting your medication from a reputable pharmacy with a prescription, you could be getting something ineffective or unsafe. You can read more about this topic here.

Bottom Line

GLP-1 agonists are very helpful medications that work, but patients taking them need to be under the direct care of a physician or other healthcare provider. Patients should have a proper work up prior to starting the medication, an attainable lifestyle modification that is regularly reviewed and tweaked, and have someone monitoring for adverse effects. Is it possible to go the emergency department when experiencing adverse effects? Of course, but waits are often long and waiting rooms are stressful. My patients call me and either meet me in my office for treatment, including intravenous fluids, or I go to their house to treat them. You can’t get that kind of care from an asynchronous visit online.

Disclaimer: Even though I’m a doctor, I’m not your doctor—and reading this blog does not establish a doctor–patient relationship. This information is intended for general educational purposes only and should not be taken as personalized medical advice. Always speak with your own healthcare provider before making decisions about your health.

References

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  2. Holst JJ. The physiology of glucagon-like peptide 1. Physiol Rev. Oct 2007;87(4):1409-39. doi:10.1152/physrev.00034.2006
  3. FDA Orange Book. FDA Orange Book.
  4. Mares AC, Chatterjee S, Mukherjee D. Semaglutide for Weight Loss and Cardiometabolic Risk Reduction in Overweight/Obesity. Current Opinion in Cardiology. 2022;37(4):350-355. doi:10.1097/HCO.0000000000000955
  5. Andersen A, Knop FK, Vilsbøll T. A Pharmacological and Clinical Overview of Oral Semaglutide for the Treatment of Type 2 Diabetes. Drugs. 2021;81(9):1003-1030. doi:10.1007/s40265-021-01499-w
  6. Davies MJ, Aroda VR, Collins BS, et al. Management of Hyperglycemia in Type 2 Diabetes, 2022. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care. 2022;45(11):2753-2786. doi:10.2337/dci22-0034
  7. De Block CEM, Dirinck E, Verhaegen A, Van Gaal LF. Efficacy and Safety of High-Dose Glucagon-Like Peptide-1, Glucagon-Like Peptide-1/Glucose-Dependent Insulinotropic Peptide, and Glucagon-Like Peptide-1/Glucagon Receptor Agonists in Type 2 Diabetes. Diabetes, Obesity & Metabolism. 2022;24(5):788-805. doi:10.1111/dom.14640
  8. Syed YY. Tirzepatide: First Approval. Drugs. 2022;82(11):1213-1220. doi:10.1007/s40265-022-01746-8
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  10. American Diabetes Association Professional Practice Committee. Obesity and weight management for the prevention and treatment of type 2 diabetes: standards of care in diabetes–2025. Diabetes Care. 2025;48(Supplement_1):S167-S180.
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  13. Health NIf. RYBELSUS. FDA Drug Label. 2024. 2024-12-09.
  14. Committee ADAPP. Older Adults: Standards of Care in Diabetes-2025. Diabetes Care. 2025;48(Supplement_1):S266-S282. doi:10.2337/dc25-S013
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  16. Burke B, Conlin PR, Giles A. Management of Type 2 Diabetes Mellitus (2023). 2023.
  17. Honigberg MC, Chang LS, McGuire DK, et al. Use of Glucagon-Like Peptide-1 Receptor Agonists in Patients With Type 2 Diabetes and Cardiovascular Disease: A Review. JAMA Cardiology. 2020;5(10):1182-1190. doi:10.1001/jamacardio.2020.1966
  18. Wang L, Volkow ND, Kaelber DC, Xu R. Semaglutide or Tirzepatide and Optic Nerve and Visual Pathway Disorders in Type 2 Diabetes. JAMA Network Open. 2025;8(8):e2526327-e2526327. doi:10.1001/jamanetworkopen.2025.26327
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  21. Karakasis P, Patoulias D, Fragakis N, Mantzoros CS. Effect of glucagon-like peptide-1 receptor agonists and co-agonists on body composition: Systematic review and network meta-analysis. Metabolism. Mar 2025;164:156113. doi:10.1016/j.metabol.2024.156113
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  25. Wing RR, Jeffery RW. Benefits of recruiting participants with friends and increasing social support for weight loss and maintenance. Journal of consulting and clinical psychology. 1999;67(1):132.
  26. Mozaffarian D, Agarwal M, Aggarwal M, et al. 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 American Journal of Clinical Nutrition. 2025;122(1):344-367. doi:10.1016/j.ajcnut.2025.04.023
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  28. Davies MJ, D’Alessio DA, Fradkin J, et al. Management of Hyperglycemia in Type 2 Diabetes, 2018. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care. 2018;41(12):2669-2701. doi:10.2337/dci18-0033
  29. Chiang CH, Jaroenlapnopparat A, Colak SC, et al. Glucagon-Like Peptide-1 Receptor Agonists and Gastrointestinal Adverse Events: A Systematic Review and Meta-Analysis. Gastroenterology. 2025;doi:10.1053/j.gastro.2025.06.003
  30. Long B, Pelletier J, Koyfman A, Bridwell RE. GLP-1 Agonists: A Review for Emergency Clinicians. The American Journal of Emergency Medicine. 2024;78:89-94. doi:10.1016/j.ajem.2024.01.010

 

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