While obesity isn’t new, the obesity epidemic is
The latest data (2024) suggest that nearly 40% of U.S. adults and 20% of children are overweight or obese. For several decades, researchers and pharmaceutical companies have tried to find a pharmacological treatment for obesity with marginal success. Until now. A whole new class of weight-loss drugs has come on the market and taken the weight-loss industry by storm.
Anti-obesity drugs
Early anti-obesity medications included appetite suppressants, like Phentophrine, which is still available, that belong to a class of drugs called sympathomimetic amines. More recent anti-obesity medications include drugs that block dietary fat absorption and/or curb hunger. The newest anti-obesity drug, Semaglutide, belongs to a class of medications that mimic the actions of the hormone GLP-1, which is released in the gut in response to eating. Another name for this medication is Glucagon-like peptide-1 receptor agonists: GLP-1 RAs.
The most popular and effective semaglutide drugs are Ozempic and Wegovy, and most recently Zepbound, containing Terzepatide, which reduces appetite and slows digestion. Wegovy contains a higher Semaglutide dose and is specifically designed for weight loss. Physicians use the lower-dose Ozempic to treat diabetes, with weight loss as a side effect. Other anti-obesity medications are currently in late-phase clinical trials and will likely become available soon. For example, monoclonal antibodies are another “hot” anti-obesity drug category, including the monoclonal antibody Bimagrumab. This infusion medication promotes increased muscle mass and loss of excess fat tissue. Bimagrumab also improves insulin resistance.
Who should (and should not) take Semaglutide
The FDA recommends Wegovy for weight loss if a person meets one of the following criteria:
- Have a body mass index (BMI) of 27 or greater and at least one weight-related co-morbidity (suffering from a disease or medical condition), such as high blood pressure, type 2 diabetes, or high cholesterol.
- Have a BMI of 30 or greater for women and men.
Individuals should avoid Semaglutide if they have a history of medullary thyroid cancer, gallbladder disease, pancreatitis, or multiple endocrine neoplasia syndrome type 2 (MEN2).
How do GLP-1 agonists work?
To understand how GLP-1 agonists work, it helps to know how the naturally occurring GLP-1 hormone works. The GLP-1 hormone is secreted by the small intestine and helps regulate blood sugar levels and manage weight by:
- Triggering the pancreas to release insulin.
- Slowing the movement of food from the stomach into the small intestine (known as delayed gastric emptying), which makes a person feel full longer.
- Promoting hormone secretions that increase feelings of fullness.
- Improving insulin signaling.
- Possibly stimulating thermogenesis (heat production resulting in increased energy expenditure) in brown adipose tissue.
In essence, GLP-1 agonists work primarily by regulating hormones in the brain, digestive system, and adipose tissue. They suppress appetite and food cravings, slow the rate of gastric emptying, and promote fullness. For some people, GLP-1 agonists also lower blood pressure, improve blood-lipid disorders, improve fatty liver disease, and reduce the risk of heart and kidney diseases.
GLP-1 agonists currently available in the U.S. include Dulaglutide (trade name Trulicity®); Exenatide (Byetta®) and Exenatide extended-release (Bydureon®); Liraglutide (Victoza®); Lixisenatide (Adlyxin®); and Semaglutide — in injections or in pill form (i.e., Ozempic® and Wegovy®). There is a similar class of medications called dual GLP-1/GIP receptor agonists like Tirzepatide (Zepbound® and Mounjaro®).
Possible complications
(Image: iStock.)
Common side effects include:
- Nausea
- Vomiting
- Diarrhea
- Constipation
- Abdominal pains
Serious side effects include:
- Pancreatitis (swelling and inflammation of the pancreas)
- Gastroparesis (weakening of the digestion muscles, causing food to remain in the stomach longer)
- Bowel obstruction (small or large intestine are blocked, preventing food and stool from passing)
- Acute kidney failure
- Diabetic retinopathy (a chronic eye condition that occurs when high blood sugar levels damage blood vessels in the retina, leading to blindness)
- Thyroid cancer and gallstone attacks that cause bile duct blockage
Semaglutide effectiveness
Research shows that Semaglutide-GLP-1 medications are safe (depending on how one reacts to side effects). They are most effective as part of a comprehensive treatment plan that includes increasing physical activity and transitioning to a more healthful diet.
According to clinical studies, the amount of weight loss possible with Semaglutide can be significant.
A 2022 study of 175 individuals showed 5.9% weight loss at three months and 10.9% at six months. A more extensive study published in the New England Journal of Medicine showed even more significant average loss — 14.9% of body weight. In a recent 2024 meta-analysis of studies in patients with overweight or obesity without diabetes, once-weekly subcutaneous Semaglutide injections significantly decreased body weight without risk of serious adverse events when compared to a placebo. The analysis showed individuals discontinued their medication due to gastrointestinal side effects.
How long do GLP-1 medications need to be taken?
American adults usually take GLP-1s for an average of six months or longer. Discontinuation is generally associated with gastrointestinal side effects and high out-of-pocket costs. Users may regain weight after stopping the medication.
Costs
GLP-1 weight-loss drugs are expensive. Without insurance, according to manufacturers’ list prices, Ozempic costs $968.52 per 28-day supply, or more than $12,600 per year. Wegovy costs about $1,349.02 per 28-day supply, or more than $17,500 annually! Only a few insurers cover the cost with a doctor’s Rx. Medicare does not cover the cost at this time. It is possible to obtain GLP-1 prescriptions online with some cost savings. Providers offer yearly sign-up programs to obtain GLP-1 medicines with different pricing plans.
The bottom line
For many individuals, GLP-1 weight-loss medications are a dream come true. They regulate blood sugar, curb appetite and food cravings, slow digestion, and, in some individuals, lower blood pressure. They also improve lipid disorders and fatty liver disease, reduce the risk of heart disease and kidney disease, and delay the progression of diabetes-related nephropathy without requiring major changes in diet or exercise habits.
But … buyer, beware
GLP-1 drugs are not without serious side effects that can include nausea, vomiting, diarrhea, constipation, muscle loss, pancreas inflammation, allergic reactions, and weight regain after stopping the medication. Most importantly, there is limited research on long-term effects and consequences. Be sure to work with a physician if you are planning to try them.
References
- Apovian, C.M., et al. Endocrine Society. “Pharmacological management of obesity: An Endocrine Society clinical practice guideline.” The Journal of Clinical Endocrinology & Metabolism 2015;100(2):342.
- Aronne, L.J., et al. “Continued treatment with Tirzepatide for maintenance of weight reduction in adults with obesity: The Surmount-4 randomized clinical trial.” JAMA 2024;331(1):38-48.
- Ghusn, W., et al. “Weight loss outcomes associated with semaglutide treatment for patients with overweight or obesity.” JAMA Network Open 2022;5(9):e2231982.
- Hampl, S.E., et al. “Clinical practice guideline for the evaluation and treatment of children and adolescents with obesity.” Pediatrics 2023;151(2):e2022060640.
- Henderson, K., et al. “Effectiveness and safety of drugs for obesity.” BMJ. 2024;384:e072686
- Kommu, S., Berg, R.L. “Efficacy and safety of once-weekly subcutaneous semaglutide on weight loss in patients with overweight or obesity without diabetes mellitus-A systematic review and meta-analysis of randomized controlled trials.” Obesity Reviews 2024;25(9):e13792.
- Moiz, A., et al. “Long-term efficacy and safety of once-weekly semaglutide for weight loss in patients without diabetes: A systematic review and meta-analysis of randomized controlled trials.” The American Journal of Cardiology 2024;222:121.
- U.S. Food & Drug Administration. “FDA approves treatment for chronic weight management in pediatric patients aged 12 years and older.” June 27, 2022.
- Weghuber, D., et al. “Once-weekly semaglutide in adolescents with obesity.” New England Journal of Medicine 2022;387:2245–2257.
- Wilding, J.P.H., et al. “Once-weekly Semaglutide in adults with overweight or obesity. New England Journal of Medicine 2021;18:384(11):989.
- Wilding J.P.H., et al. “Weight regain and cardiometabolic effects after withdrawal of semaglutide: The STEP 1 trial extension.” Diabetes, Obesity & Metabolism 2022;24(8):1553.
- Yanovski, S.Z., Yanovski, J.A. “Long-term drug treatment for obesity: A systematic and clinical review.” JAMA 2014;311(1):74.
- Yanovski S.Z., Yanovski, J.A. “Progress in pharmacotherapy for obesity.” JAMA 2021;326(2):129.
Lauren Oshman
I appreciate the inclusion of an article about weight management in Michigan Today. I am a family physician board certified in obesity medicine and I care for patients as part of the Weight Navigation Program, a specialty center dedicated to comprehensive obesity care at the University of Michigan Medical Group (https://www.uofmhealth.org/conditions-treatments/weight-navigation-program).
The author describes older medications as having “marginal success.” For many people living in larger bodies, weight loss is not indicated. When we take a weight inclusive approach to health care, we utilize treatment to focus on a person’s health, not just their weight. We know that 5% weight loss can lead to durable health improvements.
I find the characterization of weight loss as an “industry” and drugs as “hot” concerning. As with any treatment, patients should work with a physician or advance practice provider that they trust and who is knowledgeable about their health condition. We show in our recent article that patients who see an obesity medicine specialist at U of M have better outcomes than those who receive care in general settings. (https://pubmed.ncbi.nlm.nih.gov/38771575/)
The author mischaracterizes the side effects of incretin mimetics. Particularly, people with multiple endocrine neoplasia syndrome 2 and medullary thyroid cancer should not be prescribed incretin mimetics, but data thus far do not support a link between incretin mimetics and thyroid cancer (https://www.bmj.com/content/385/bmj-2023-078225).
The author uses the term Semaglutide-GLP-medications. This is “not a thing” and incretin mimetics or the newer term NUSH (nutrient stimulated hormones) better characterize the generic category of these medications. Incretin mimetics are unaffordable for many of my patients. President Biden listed brand name Wegovy as a possible medication for price negotiation for Medicare (https://www.npr.org/sections/shots-health-news/2025/01/17/nx-s1-5262886/drugs-medicare-price-negotiation-biden-ozempic) and I sincerely hope that the Trump administration will continue to work to reduce price gouging by pharmaceutical companies like Novo Nordisk and Lilly, the maker of tirzepatide.
The article describes few insurances as covering these medications. Partly due to the advocacy of a small group of physicians in Michigan, Medicaid now covers incretin mimetics for obesity and overweight with comorbidities, but has a number of utilization requirements to help manage the very high costs of these medications with their benefit for selected patients (https://deepblue.lib.umich.edu/handle/2027.42/172493).
Medicare covers incretin mimetic, the more generic term for medications such as semaglutide, tirzepatide, and liraglutide, for certain conditions, hence raising the possibility of price negotiation.
We recently surveyed physicians about Blue Cross Blue Shield of Michigan eliminating coverage for incretin mimetics and are actively researching mechanisms to help patients reduce weight regain. (https://deepblue.lib.umich.edu/handle/2027.42/195203)
Finally the author states “plan to work with a physician if you are planning to try them.” I cannot state more strongly that patients should not utilize any prescription medication without a prescription from a physician. There are reported deaths from patients using non-FDA approved compounded GLP medications (https://www.reuters.com/business/healthcare-pharmaceuticals/novo-nordisk-says-it-is-aware-10-deaths-compounded-weight-loss-drug-copies-2024-11-06/) and our professional societies advise against the use of non-FDA approved options.
I greatly appreciate the inclusion of this topic in Michigan Today and the opportunity to both correct some factual errors and tie this important topic to the work our Weight Navigation Team is doing to help patients every day.
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