Glucagon-like peptide (GLP)–1 inhibitors are being studied for the treatment of obesity-related comorbidities such as obstructive sleep apnea (OSA), substance use disorder (SUD), heart failure, chronic kidney disease (CKD), and more. A session at the AMCP 2025 Annual Meeting provided an overview of the research pipeline and how these therapies may affect the treatment paradigm.
In OSA, the SURMOUNT trials assessed tirzepatide versus placebo for change in apnea-hypopnea index (AHI) score. The 52-week, phase 3 study included adults with an average BMI of 39 kg/m2. In the first trial (n=234), tirzepatide resulted in a –25.3 change in AHI compared with –5.3 with placebo (P<0.001). In the second trial (n=236), change in AHI was –29.3 and –5.5, respectively (P<0.001).
In these 2 trials, tirzepatide also resulted in greater percent change in weight (–17.7 and –19.6, respectively) compared with placebo (–1.6 and –2.3, respectively). Health plans may need to consider a pathway for GLP-1s for OSA that do not require other weight loss drugs.
Only 4.5% of people aged 12 years and older received SUD treatment in the last year; thus, new treatment options are needed. Several studies have assessed the effect of GLP-1s on tobacco, alcohol, and cocaine use disorders. The exact mechanism of impact is unknown, but positive effects are likely due to nonspecific anti-consummatory properties, according to the presentation. Ongoing studies will provide more insights into the future utilization of GLP-1s for SUDs.
Three studies have assessed the use of tirzepatide and semaglutide for the treatment of heart failure with preserved ejection fraction (HFpEF). The SUMMIT trial showed that tirzepatide improved clinical outcomes in terms of decreased cardiovascular death or worsening heart failure events. The STEP HFpEF trials found that semaglutide improved quality of life and functional end points and resulted in greater weight loss than placebo. Obesity is a driving factor for HFpEF development, and health plans should ensure clear guideline-supported therapies for HFpEF are followed first.
Type 2 diabetes is the most common cause of CKD, with 40% of patients affected. Chronic kidney disease also increases costs in this patient population by 50%. There is a relationship between obesity in CKD, as progression to end-stage renal disease occurs more quickly in those with obesity and CKD. A twin study of nearly 30,000 individuals estimated that nearly a third (32%) of CKD cases are attributed to a BMI greater than 25 kg/m2.
The FLOW trial assessed the use of semaglutide versus placebo in adults with type 2 diabetes and CKD. Patients treated with semaglutide (n=1,767) had 331 (18.7%) major kidney events compared with 410 (23.2%) in placebo-treated patients (n=1,766; P=0.0003), demonstrating a −24% reduction in major kidney disease outcomes in patients with type 2 diabetes.
Payers should continue to closely monitor the GLP-1 pipeline, which may result in approvals for GLP-1s for these and other conditions in 2025 and beyond.
Reference
Lugo A, Allerman A, Patti K. GLP-1’s for everything! The gift that keeps on giving – an evidence review and managed care implications. Presented at: AMCP 2025; March 31-April 3, 2025; Houston, TX. Session K2.
