GLP-1 Side Effects Have a Side Effect on Pharmacy Costs| AMCP Annual 2025

Glucagon-like peptide 1 (GLP-1) treatment resulted in side effects that often required additional medications, increasing overall pharmacy use and costs among GLP-1 drugs compared with nonusers, according to a real-world claims analysis completed by Blue Cross Blue Shield Association (BCBSA) and Blue Health Intelligence (BHI) that was presented as a poster at the annual meeting of the Academy of Managed Care Pharmacy in Houston this week

When excluding the costs of the GLP-1 drugs themselves, after one year the overall pharmacy costs were $1,449 higher for those prescribed a GLP-1 compared with the matched controls who were not taking one. These trends continued to expand as time went on, with the costs increasing to a $2,390 difference at two years and to $2,812 at three. When including the costs of the GLP-1 medication, the cost differences were $9,200, $8,371, and $8,660 at one, two and three years, respectively.

Henriette Coetzer, M.D.

"GLP-1 treatment-related side effects often require additional medications, increasing overall pharmacy utilization and costs beyond the direct expense of GLP-1 therapy," Henriette Coetzer, M.D., the chief medical officer and senior vice president at BHI, and her colleagues concluded in their poster. “Payers should account for the burden of managing these side effects when assessing the overall cost burden of GLP-1 treatment.”

From "Real-world trends in pharmacy utilization among commercially insured individuals treated with glucagon-like peptide 1 receptor agonists (GLP-1s), 2014-2024," Coetzer H et al., AMCP Annual 2025 meeting poster

"In the research we publish today at AMCP, we show that some side effects of GLP-1 treatment last longer than previously known and that they may be troublesome enough to require ongoing medication and medical care," Coetzer told Managed Healthcare Executive (MHE). "Understanding the full picture of costs and benefits helps payers design payment structures and support programs that ensure that members have the best chance of a successful treatment outcome and that keep medical inflation in check."

Using the claims database, BCBSA and BHI identified over two million insured individuals with a claim for a GLP-1 drug between January 2014 and April 2024. From that group, they narrowed the age to those between 18 and 64 years and those who had coverage for at least six months prior to the study. The exclusion criteria removed individuals with cancer, transplants, dementia, dialysis and psychosis within 2 years prior to the study date from their analysis. The propensity-matching design of the study made the GLP-1 users comparable to their non-GLP-1 counterparts as far as age, gender, obesity, Type 2 diagnosis and other factors. The end result was a study that allowed Coetzer and her colleagues to compare 1,096,209 individuals taking GLP-1s compared with 2,605,842 individuals not taking them.

Persistence of GLP-1 treatment correlated with an increase in gastrointestinal side effects that warranted additional treatment. The occurrence of gastroesophageal reflux disease (GERD) requiring treatment was 25% from months 0 to 12 for those taking a GLP-1. This proportion increased to 28% at months 13-24 and to 32% at month 24 and beyond. Similarly, the proportion of GLP-1 users with constipation or diarrhea increased as time went on, from 11% at months 0-12 to 14% at months 13-24 and to 20% from 24 months and beyond. But rates of nausea and vomiting remained steady at 20%, 22% and 21% for months 0-12, 13-24, and 24 and beyond, respectively.

When comparing the GLP-1 users and nonusers for postinitiation treatment prevalence, there was a 5.8 percentage point difference in the rates of GERD, at 25% for the GLP-1 users versus 19% for the nonusers. There was a 7.1 percentage point difference for nausea and vomiting, at 19% for the GLP-1 users and 12% for the non-users. After rounding, constipation and diarrhea rates were 11% and 10% for GLP-1 users and non-users, respectively.

The GLP-1s that patients used were not specified by Coetzer and her colleagues. Although use of the GLP-1s has taken off in the past several years after they started to be used for weight loss, they were approved as treatment for diabetes 15 years ago. Victoza (liraglutide) was approved by the FDA in 2010 and Trulicity (dulaglutide) in 2014, both of which would have been available during the study. Other GLP-1s, such as Byetta (exenatide) and Adlyxin (lixisenatide), were also available during the period that this study covered, although the latter was discontinued in 2023. Now-famous Ozempic (semaglutide) was initially approved in 2017 and Mounjaro (tirzepatide) in 2022, both of which are the more commonly used GLP-1s in recent years. They have been subsequently approved and marketed explicitly for weight loss, semaglutide under the brand name Wegovy and tirzepatide under the brand name Zepbound.

BCBSA and BHI launched a program of research into the use and effects of GLP-1 medications in the real world two years ago, Coetzer told MHE. "This joint work has already provided valuable insights that help patients, providers and payers understand who these drugs work best for and how to make their cover affordable for those who most need them."