GLP‑1s: benefits and tradeoffs

These drugs mimic gut hormones that slow stomach emptying and curb appetite, and the strongest weight-loss results keep coming from semaglutide and tirzepatide. (ajmc.com) A November 18, 2025 American Journal of Managed Care report summarized a Journal of Obesity review of 22 randomized trials lasting at least 40 weeks in more than 40,000 adults. It said semaglutide 2.4 mg and tirzepatide 5 mg, 10 mg, and 15 mg delivered the largest weight losses in adults with and without type 2 diabetes. (ajmc.com) The review also found liraglutide trailed those newer drugs on weight loss but could become a cheaper option as patent protection winds down. In the same roundup, gastrointestinal problems such as nausea and vomiting were common, while pancreatitis and serious adverse events were similar to placebo across the trials reviewed. (ajmc.com) The basic tradeoff is simple: the medicines that move the scale the most also come with side effects that many patients feel week to week. The Food and Drug Administration labels for Wegovy and Zepbound list nausea, diarrhea, vomiting, constipation, and abdominal pain among the most common reactions. (accessdata.fda.gov, accessdata.fda.gov) Head-to-head data sharpened that picture in 2025. In SURMOUNT-5, published in the New England Journal of Medicine on May 11, 2025, adults with obesity but without diabetes lost 20.2% of body weight on tirzepatide over 72 weeks, versus 13.7% on semaglutide. (news.weill.cornell.edu, investor.lilly.com) That trial enrolled 751 people at 32 sites in the United States and Puerto Rico, and about 32% of patients on tirzepatide lost at least a quarter of their body weight, compared with 16% on semaglutide. Investigators also reported similar side-effect patterns in both groups, with nausea affecting about 44% in each arm and abdominal pain about 25%. (news.weill.cornell.edu, investor.lilly.com) The drugs’ reach now extends beyond clinic visits and insurance claims into relationships and family planning. A SELF article published April 20, 2026 described women hiding Wegovy pens in hotel fridges, food containers, and supplement bottles to keep their use from partners and relatives. (health.yahoo.com) In that article, Jacksonville obesity-medicine physician Kia Mitchell said patients in her practice have concealed the medication from partners, and one 34-year-old Montreal woman described restarting Wegovy at a maintenance dose after regaining 10 pounds in a month when she stopped. The piece also noted pregnancy concerns, with Mitchell saying fertility can increase as weight falls and cycles normalize. (health.yahoo.com) Another new line of concern is sexual side effects in men with diabetes, though the evidence is early and limited. A Medindia report published April 20, 2026 said an observational study linked glucagon-like peptide-1 receptor agonists to a modest increase in erectile dysfunction risk in men with type 2 diabetes, and outside experts in follow-up coverage said the evidence is not conclusive. (medindia.net, msn.com) For patients and doctors, the current map is clearer than it was a year ago: tirzepatide and semaglutide lead on pounds lost, liraglutide may matter more on price, and the real-world decision now includes nausea, privacy, pregnancy planning, and the possibility of side effects that trials may only partly capture. (ajmc.com, accessdata.fda.gov, accessdata.fda.gov, health.yahoo.com, medindia.net)