Diabetes Dialogue: STEP HFpEF DM and Fair Allocation of Incretin-Based Therapies

In this episode of Diabetes Dialogue: Technology, Therapeutics, & Real-World Perspectives, hosts Diana Isaacs, PharmD, an endocrine clinical pharmacist, director of Education and Training in Diabetes Technology, and codirector of Endocrine Disorders in Pregnancy at the Cleveland Clinic, and Natalie Bellini, DNP, program director of Diabetes Technology at University Hospitals Diabetes and Metabolic Care Center, tackle a pair of related topics: what the STEP HFpEF DM trial from ACC.24 means for the diabetes community and the need for fair and equitable allocation of incretin-based therapies in the face of ongoing drug shortages and overwhelming demand.

STEP HFpEF DM

Presented at ACC.24 and simultaneously published in the New England Journal of Medicine, STEP HFpEF DM was a randomized, double-blind, placebo-controlled trial that randomized 616 participants in a 1:1 ratio to semaglutide 2.4 mg or placebo therapy for 52 weeks. Conducted across 108 sites in 16 countries across Asia, Europe, and North and South America, inclusion criteria for the study required patients to have a left ventricular ejection fraction of 45% or greater, a BMI of 30 kg/m2 or greater, and type 2 diabetes.¹

Like the original STEP HFpEF trial, STEP HFpEF DM had dual primary endpoints, which were change from baseline in Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS) and change in body weight. STEP HFpEF DM also included multiple secondary confirmatory endpoints, these included change in 6-minute walk distance, a hierarchical composite end point of death, heart failure events, and differences in the change in the KCCQ-CSS and 6-minute walk distance, and the change in the C-reactive protein (CRP) level.¹

Results of the trial indicated use of semaglutide 2.4 mg was associated with a mean change from baseline KCCQ-CSS of 13.7 points compared to a 6.4-point change with placebo therapy (Estimated treatment difference [ETD], 7.3 points; 95% CI, 4.1 to 10.4; P < .001). Analysis of body weight suggested the mean change from baseline was −9.8% with semaglutide 2.4 mg and −3.4% with placebo therapy (ETD, −6.4 percentage points; 95% CI, −7.6 to −5.2; P < .001). Further analysis indicated pointed to benefit withsemaglutide 2.4 mg over placebo therapy for change in 6-minute walk distance (estimated between-group difference, 14.3 meters; 95% CI, 3.7 to 24.9; P = .008), the hierarchical composite endpoint (win ratio, 1.58; 95% CI, 1.29 to 1.94; P < .001), and change in CRP level (estimated treatment ratio, 0.67; 95% CI, 0.55 to 0.80; P < .001).¹

Fair and Equitable Allocation of Incretin-Based Therapies

Aptly timed and also published in the New England Journal of Medicine, an editorial penned by a group of 5 from the Department of Medical Ethics and Health Policy at the Perelman School of Medicine of the University of Pennsylvania and the Bergen Center for Ethics and Priority Setting at the University of Bergen brought forth ethical perspectives on the fair allocation of GLP-1 receptor agonists and dual GLP-1/GIP receptor agonists in the face of overwhelming demand and changing coverage of these agents.²

In their editorial, the group proposes a 4-tiered system for allocation based on objectives of care and specified distribution criteria. In hierarchical order, these objectives are: to minimize potential years of life lost, prevent imminent medical complications, prevent future medical complications, and improve quality of life. In their discussion, Isaacs and Bellini discuss their real-world experience in balancing this issue as new data and indications continue to emerge.²

References:

1. Campbell P. Step HFPEF DM: Semaglutide 2.4 mg improves functional status, symptoms in patients with diabetes, HFPEF. HCP Live. April 6, 2024. Accessed April 17, 2024. https://www.hcplive.com/view/step-hfpef-dm-semaglutide-2-4-mg-improves-functional-status-symptoms-in-patients-with-diabetes-hfpef.
2. Emanuel EJ, Dellgren JL, McCoy MS, Persad G. Fair Allocation of GLP-1 and Dual GLP-1–GIP Receptor Agonists. N Engl J Med. Published online April 17, 2024. doi:10.1056/NEJMp2400978