First-Line Therapy for Type 2 Diabetes With Sodium-Glucose Cotransporter-2 Inhibitors and Glucagon-Like Peptide-1 Receptor Agonists : A Cost-Effectiveness Study

Abstract

Background: Guidelines 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.

Objective: To evaluate the lifetime cost-effectiveness of a strategy of first-line SGLT2 inhibitors or GLP1 receptor agonists.

Design: Individual-level Monte Carlo-based Markov model.

Data sources: Randomized trials, Centers for Disease Control and Prevention databases, RED BOOK, and the National Health and Nutrition Examination Survey.

Target population: Drug-naive U.S. patients with type 2 diabetes.

Time horizon: Lifetime.

Perspective: Health care sector.

Intervention: First-line SGLT2 inhibitors or GLP1 receptor agonists.

Outcome measures: Life expectancy, lifetime costs, incremental cost-effectiveness ratios (ICERs).

Results of base-case analysis: First-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 analysis: By 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.

Limitation: U.S. population and costs not generalizable internationally.

Conclusion: As 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 source: American Diabetes Association.

Figure.

Medication treatment algorithms. * A₁c = hemoglobin A₁c; ASCVD = atherosclerotic cardiovascular disease; CKD = chronic kidney disease; CKD4 = chronic kidney disease stage 4; eGFR = estimated glomerular filtration rate; DPP-4 = dipeptidyl peptidase-4 inhibitor; GLP1 = glucagon-like peptide-1 receptor agonist; SGLT2 = sodium-glucose cotransporter-2 inhibitor; SU = sulfonylureas; TZD = thiazolidinediones. * The same population was compared using each of the 3 medication treatment algorithms. † Patients with CKD4 should not start an SGLT2, and should stop one that has been started; SGLT2 should be stopped and not started. ‡ DPP-4 inhibitors were added in the first-line GLP1 receptor agonist strategy only if the GLP1 receptor agonist was discontinued due to adverse events.