Semaglutide for the secondary prevention of cardiovascular disease in people with overweight or obesity, but without diabetes: a cost-effectiveness analysis
Authors: Zomer E , Zhou J , Nelson A J , Nicholls S J , Stub D , Zoungas S 
Published: October 2024

Abstract

Background
The recently published trial, SELECT (Semaglutide Effects on Cardiovascular Outcomes in People with Overweight or Obesity) [1], was the first study to demonstrate that the glucagon-like peptide 1 receptor agonist, semaglutide, was superior to placebo in reducing the risk of major cardiovascular events in people with existing cardiovascular disease (CVD) and a body mass index of ≥27kg/m² but without diabetes. Despite the promising clinical benefits, the high cost of the medication has raised concerns about its financial viability and accessibility within healthcare systems.

Purpose
To explore whether use of semaglutide in addition to standard care (background use of lipid lowering, anti-hypertensive and/or anti-platelet therapies) for the secondary prevention of CVD in people with overweight or obesity is cost effective from the Australian healthcare perspective.

Methods
A Markov model was developed based on the SELECT trial, to evaluate the clinical outcomes and costs of a hypothetical population treated with semaglutide versus placebo over 20 years. With each annual cycle, subjects were at risk of having non-fatal CVD events (MI or stroke) or dying. Treatment efficacy, transition probabilities, and utilities were derived from the SELECT trial and published literature. Costs were obtained from Australian sources. The cost of semaglutide at a dosage of 2.4 mg/week (in line with SELECT) was estimated to be ~A$80 per week or A$4175 per year. The main outcome of interest was the incremental cost-effectiveness ratio (ICER) in terms of cost per year of life saved (YoLS) and cost per quality-adjusted life year (QALY) gained. All outcomes and costs were discounted by 5% per year. Costs are reported in 2023 Australian dollars (A$).

Results
Over a 20 year time horizon, treatment of 1000 hypothetical subjects with overweight or obesity and existing CVD with semaglutide compared to placebo prevented 126 non-fatal CVD events and 81 deaths, and yielded an additional 0.46 discounted life years and 0.48 discounted QALYs per person. The difference in total discounted costs was A$43,955 per person. This equated to ICERs of A$99,853 per YoLS and A$96,055 per QALY gained.

Conclusions
Assuming a willingness-to-pay-threshold of A$50,000 per QALY gained, semaglutide would not be considered cost-effective for the secondary prevention of CVD in people with overweight or obesity in Australia at current prices. A price reduction of 52% to less than A$2000 per year would be required for it to be considered a cost-effective treatment strategy in this setting. Given the modest event rates reported in SELECT, cost-effectiveness is likely to improve if use of semaglutide is targeted to higher risk groups. Moreover, SELECT primarily focused on cardiovascular benefits, however data supporting the impact of semaglutide on a number of other weight-related complications are anticipated and will inform a more holistic understanding of its cost effectiveness.