ICER Finds GLP-1 Drugs Cost-Effective but Warns of Major Budget Strain

Treatment with Wegovy (semaglutide), the investigational oral semaglutide and Zepbound (tirzepatide) was deemed cost-effective with increased quality of life and fewer cardiovascular events, according to a preliminary draft evidence report from The Institute for Clinical and Economic Review (ICER) on comparative effectiveness and value.

But researchers raised concerns about the affordability of these three GLP-1 drugs to treat patients with obesity. Although the prices of the three drugs studied fall within accepted cost-effectiveness thresholds, widespread demand creates enormous budget pressures on payers, employers, and patients. At current prices, ICER researchers estimate that fewer than 1% of eligible patients could be treated before crossing the ICER budget impact threshold of $880 million annually.

With up to 40% of the U.S. population potentially eligible for treatment with GLP-1 drugs for obesity, payers and policymakers and other experts question how they provide coverage that is affordable for patients. The demand for GLP-1 drugs for weight loss is increasing. A PwC survey in October 2024 found that 8% to 10% of Americans are currently taking GLP-1 drugs, and 30% to 35% of Americans are interested in using them.

Related: ICER Finds Insurers Struggled to Provide Fair Access for Obesity Drugs

Coverage decisions for GLP-1 drugs that treat obesity remain complicated. Many payers acknowledge the drugs’ clinical value but struggle to balance them against other healthcare priorities.

In this review, ICER evaluated the available clinical evidence for Zepbound, Wegovy and oral semaglutide — which is currently being reviewed by regulators with an expected decision in December 2025 — in people with obesity and without diabetes compared with lifestyle interventions or no specific intervention. In cost-effectiveness analyses, researchers used estimated net prices from SSR Health of $6,830 for Wegovy and $7,973 for Zepbound. They assumed the price of oral semaglutide would be the same as Wegovy.

All three drugs generally improved health-related quality of life and metabolic risk factors such as blood pressure, blood glucose and lipids. Researchers found that treatment with all three drugs resulted in substantial weight loss compared with placebo, with a mean difference in weight loss compared with placebo of -17.8% with Zepbound treatment, -13.1% with Wegovy treatment, and -11.4% with oral semaglutide treatment. Greater weight loss with Zepbound than with Wegovy was also seen in head-to-head trials.

David Rind, M.D.

“We know tirzepatide works better and has likely fewer side effects than semaglutide, but to be able to say which is the better drug for cardiovascular disease, we don’t really know yet,” David Rind, M.D., ICER’s chief medical officer, said in an interview.

Adherence issues

Keeping patients on treatment remains challenging, and those who discontinue their treatment regain weight and lose the gains seen with improved metabolic function. “I don’t think we understand adherence for these drugs; the studies that we have looked at had to deal with the fact that cost insurance coverage was changing and there were shortages,” Rind said.

Side effects may be one reason that some patients stop taking these weight loss drugs. Gastrointestinal symptoms, including nausea and constipation, are common with the GLP-1 drugs. The ICER analysis found that three-quarters of patients taking either injectable Wegovy or oral semaglutide reported gastrointestinal (GI) side effects. For Zepbound, 20% to 40% of patients reported nausea, diarrhea, or constipation in the clinical trials. Physicians manage them by gradually titrating doses, advising hydration and encouraging dietary adjustments.

But what is seen in clinical trials may not match what happens in the real world. “People in clinical trials always do better than people in the real world on average,” Rind said. “People who enroll in clinical trials are healthier. They live longer, and they just do better. There are nurses calling up and making sure they don’t forget doses.”

Other patients may stop taking the medications after reaching their goal weight, but Rind emphasized that GLP-1 drugs should be considered chronic therapies, similar to the statins that are used to lower and maintain cholesterol, rather than short-term interventions.

“We don’t have any evidence that these drugs can be taken for a period of time to lose weight and then stopped,” Rind said. “We certainly don’t know if the large benefits that you get from these drugs on cardiovascular endpoints are maintained if patients stop taking them.”

Obesity is a complex disease with psychological and biological factors playing roles. Depression can contribute to weight fluctuations, and mental health can be a factor. While some studies suggest GLP-1s improve mental health, relationship dynamics and emotional challenges remain important considerations, Rind said.

Rind described obesity as partly a disorder of brain “set points” that drive persistent hunger signals, which GLP-1s appear to reset, making sustained weight loss possible for more patients.

“I don’t think we totally understand obesity,” Rind said. “Some signals are in the brain, some are in the gut, and some are in the fat cells. It’s right to think about obesity as a disorder or disease and to treat it as such. But it’s not like this came out of nowhere. It's the combination of evolutionary pressures and a world situation where you have lots of access to calories.”

ICER will be accepting comments on this draft until Oct. 6, 2025, with an evidence report issued Oct. 29. The final evidence report will be available on Dec. 19, 2025.