Focus on Diabetes and Weight-Loss Medications

In this issue of Worst Pills, Best Pills News, there are four articles about semaglutide (OZEMPIC, RYBELSUS, WEGOVY), a glucagon-like peptide-1 (GLP-1) receptor agonist, and tirzepatide (MOUNJARO, ZEPBOUND), a dual glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 receptor agonist.

Semaglutide, first approved by the Food and Drug Administration (FDA) in 2017, and tirzepatide, first approved in 2022, are widely used for type 2 diabetes, as well as for chronic weight management by people who are obese or overweight. Wegovy was first approved for weight loss in 2021, and Zepbound in 2023.

One article reviews semaglutide; another article reviews tirzepatide. The third article reviews Wegovy for metabolic dysfunction-associated steatohepatitis (MASH), a serious liver disease characterized by chronic inflammation and scarring, an indication approved in 2025.

The fourth article reports on a 2025 cohort study comparing the gastrointestinal safety of dulaglutide (TRULICITY, another GLP-1 receptor agonist), semaglutide and tirzepatide in adults with type 2 diabetes.[1] The study found that the medicines had similar safety profiles for severe gastrointestinal adverse events, defined as a composite of acute pancreatitis, biliary disease, bowel obstruction, gastroparesis (delayed stomach emptying) and severe constipation. The most common adverse reactions to semaglutide and tirzepatide are gastrointestinal. Moreover, because the drugs delay emptying of the stomach, they can affect the absorption of oral medications.

Previously, Public Citizen’s Health Research Group has classified the family of GLP-1 receptor agonist drugs as Do Not Use, most recently in 2023.[2],[3],[4] Based on the evidence at the time, we were concerned about the benefits of the drug class for type 2 diabetes and serious adverse effects.

More recent evidence, however, has established the effectiveness of semaglutide and tirzepatide for type 2 diabetes. Evidence has also established the effectiveness of the medications for chronic weight management, in conjunction with a reduced-calorie diet and increased physical activity. Moreover, the drugs have additional FDA-approved indications: Ozempic for cardiovascular and kidney disease risk reduction in adults with type 2 diabetes, Wegovy for cardiovascular disease risk reduction in adults with obesity or overweight and for MASH, and Zepbound for moderate to severe sleep apnea in adults with obesity.

Although GLP-1 drugs must be taken continuously (perhaps indefinitely) to maintain their beneficial effects and there are important safety concerns to consider, we are removing the Do Not Use designation for semaglutide, tirzepatide and the GLP-1 drug class.

Public Citizen’s Health Research Group continues to recommend that you Do Not Use compounded semaglutide, tirzepatide or other GLP-1 products.[5] Compounded drugs, regardless of how they are manufactured or marketed, are subject to a lower regulatory standard than FDA-approved products.

In February 2026 the FDA announced it was taking “decisive steps to restrict GLP-1 active pharmaceutical ingredients (APIs) intended for use in non-FDA-approved compounded drugs that are being mass marketed by companies including Hims & Hers and other compounding pharmacies as similar alternatives to FDA-approved drugs.”

As the agency “cannot verify quality, safety or efficacy” of unapproved medications, the FDA’s regulatory actions are urgently needed. Moreover, the FDA must continue its crackdown on illegal marketing of compounded GLP-1 drugs. In March 2026 the FDA sent 30 warning letters to telehealth companies for claims about compounded GLP-1 products offered on their websites that the agency considered “false or misleading.”

If you are taking or considering taking a GLP-1 medication for diabetes or weight loss, there are important things you should know, as discussed in a recent article in JAMA Internal Medicine. First, because the medications cause loss of muscle and fat, your diet should include sufficient protein. Second, because the medications reduce appetite, smaller meals and snacks may be preferred, as well as carbohydrates that are slowly digested, such as sweet potatoes or oatmeal. Third, the digestive side effects of nausea and vomiting can be minimized by avoiding high-fat foods, including foods that are fried. Fourth, because GLP-1 medications can cause dehydration, drinking sufficient fluids each day is important: two to three liters (8-12 cups) of mainly water but also soups, vegetables and fruits. Fifth, extreme calorie restriction should be avoided in combination with GLP-1 drugs because this can lead to excessive weight loss, fatigue, dehydration and kidney problems. Finally, the best way to maintain weight loss if you stop taking the medications is to continue lifestyle changes such as regular physical activity and healthy eating, including adequate protein in the diet.
 

References

[1] Crissafulli S, Alkabbani W, Paik JM, et al. Comparative gastrointestinal safety of dulaglutide, semaglutide, and tirzepatide in adults with type 2 diabetes. Ann Intern Med 2026;179(1); 1-11. doi: 10.7326/ANNALS-25-01724.Epub 2025 November 4, 2025.

[2] “Do Not Use” type 2 diabetes gliptin drugs also raise risk of gallbladder inflammation. Worst Pill, Best Pills News. March 2023. https://www.worstpills.org/newsletters/view/1521. Accessed February 18, 2026.

[3] Semaglutide (WEGOVY) for weight loss: substantial risks, including weight regain. Worst Pills, Best Pills News, August 2023. https://www.worstpills.org/newsletters/view/1545 Accessed February 19, 2025.

[4] Tirzepatide (MOUNJARO): Another diabetes drug seeking FDA approval for weight loss. Worst Pills, Best Pills News. October 2023. https://www.worstpills.org/newsletters/view/1558. Accessed February 18, 2026.

[5] Compounded injectable semaglutide and tirzepatide: bad choices for any use. Worst Pills, Best Pills News. December 2024.