• Jin G Choi, Aaron N Winn, M Reza Skandari, Melissa I Franco, Erin M Staab, Jason Alexander, Wen Wan, Mengqi Zhu, Elbert S Huang, Louis Philipson, and Neda Laiteerapong.
• Section of General Internal Medicine, Department of Medicine, University of Chicago, Chicago, Illinois (J.G.C., M.I.F., E.M.S., J.A., M.Z.).
• Ann. Intern. Med. 2022 Oct 1; 175 (10): 139214001392-1400.

BackgroundGuidelines recommend sodium-glucose cotransporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP1) receptor agonists as second-line therapy for patients with type 2 diabetes. Expanding their use as first-line therapy has been proposed but the clinical benefits may not outweigh their costs.ObjectiveTo evaluate the lifetime cost-effectiveness of a strategy of first-line SGLT2 inhibitors or GLP1 receptor agonists.DesignIndividual-level Monte Carlo-based Markov model.Data SourcesRandomized trials, Centers for Disease Control and Prevention databases, RED BOOK, and the National Health and Nutrition Examination Survey.Target PopulationDrug-naive U.S. patients with type 2 diabetes.Time HorizonLifetime.PerspectiveHealth care sector.InterventionFirst-line SGLT2 inhibitors or GLP1 receptor agonists.Outcome MeasuresLife expectancy, lifetime costs, incremental cost-effectiveness ratios (ICERs).Results Of Base Case AnalysisFirst-line SGLT2 inhibitors and GLP1 receptor agonists had lower lifetime rates of congestive heart failure, ischemic heart disease, myocardial infarction, and stroke compared with metformin. First-line SGLT2 inhibitors cost $43 000 more and added 1.8 quality-adjusted months versus first-line metformin ($478 000 per quality-adjusted life-year [QALY]). First-line injectable GLP1 receptor agonists cost more and reduced QALYs compared with metformin.Results Of Sensitivity AnalysisBy removing injection disutility, first-line GLP1 receptor agonists were no longer dominated (ICER, $327 000 per QALY). Oral GLP1 receptor agonists were not cost-effective (ICER, $823 000 per QALY). To be cost-effective at under $150 000 per QALY, costs for SGLT2 inhibitors would need to be under $5 per day and under $6 per day for oral GLP1 receptor agonists.LimitationU.S. population and costs not generalizable internationally.ConclusionAs first-line agents, SGLT2 inhibitors and GLP1 receptor agonists would improve type 2 diabetes outcomes, but their costs would need to fall by at least 70% to be cost-effective.Primary Funding SourceAmerican Diabetes Association.

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