Cost-effectiveness of semaglutide for secondary prevention of cardiovascular disease in the United States

Abstract Background In the SELECT trial, semaglutide produced a 20% reduction in the composite of cardiovascular death, non-fatal myocardial infarction (MI), and non-fatal stroke in individuals with overweight or obesity who did not have diabetes but had established pre-existing cardiovascular disease (CVD). Cost is an important barrier to widespread uptake of semaglutide, particularly in the US, and the cost-effectiveness for the secondary prevention of CVD is uncertain. Purpose To evaluate the cost-effectiveness of semaglutide vs. no obesity treatment for the secondary prevention of CVD from a US healthcare sector perspective. Methods The CVD Policy Model is an established, validated simulation model of fatal and non-fatal CVD outcomes and costs in the US population. Using data from the National Health and Nutrition Examination Survey, we created a nationally representative cohort of SELECT-eligible individuals (age ≥45, BMI ≥27kg/m2, no diabetes, pre-existing CVD). Healthcare costs associated with acute and chronic CVD were estimated from national survey and claims data and inflated to 2023 US dollars. The simulated control arm received usual care; the intervention arm received weekly semaglutide 2.4mg injections (assuming 8% discontinuation, which occurs year one). We reproduced the effectiveness of semaglutide based on results of the SELECT trial primary cardiovascular composite endpoint (non-fatal MI, non-fatal strokes and CVD death). The base case assumed 7% of patients receiving semaglutide developed injection-site reactions. Monthly cost of semaglutide was assumed to be $717 (US price net of rebates and discounts), but this was varied in sensitivity analyses. The analysis adopted a health system perspective over lifetime horizon. Results Approximately 4.7 million US adults would meet SELECT trial eligibility criteria. Over a lifetime horizon, semaglutide is projected to avert 538,000 major adverse cardiovascular events (241,000 nonfatal MIs; 80,000 nonfatal stokes, and 217,000 cardiovascular deaths) at an incremental cost of $613 billion. The incremental cost effectiveness ratio for semaglutide was $443,000 per quality-adjusted life year (QALY) gained. In order to meet cost-effectiveness thresholds of $50,000/QALY, $100,000/QALY, $150,000/QALY, drug costs would have to decline 90%, 79%, and 69% respectively. In sensitivity analyses, lowering drug cost to the current UK price (~ $220 per patient per month) would improve the incremental cost-effectiveness of semaglutide to <$150,000 per QALY gained, a potential upper threshold for cost-effectiveness in the US. Conclusion Widespread uptake of semaglutide in the SELECT-eligible U.S. population would prevent a large number of cardiovascular events, but its use would be low economic value at current US prices. Lowering prices in line with those in Europe (e.g., monthly price from $717 to $223) would make the therapy cost-effective at a threshold of $150,000 per QALY gained.