First-Line Therapy for Type 2 Diabetes With Sodium–Glucose Cotransporter-2 Inhibitors and Glucagon-Like Peptide-1 Receptor Agonists: A Cost-Effectiveness Study
Open accessAbstract
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.
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The available literature on pharmacoeconomic studies of GLP-1 receptor agonists is conflicting.
“While some pharmacoeconomic studies are available on GLP-1 receptor agonists, the available literature is conflicting and further studies with better economic modeling for data analysis are required.[47][48][49]”
From Tirzepatide: Clinical review of the twincretin injectable (2023) · cites this paper as [49]
The paper discusses existing GLP-1 receptor agonist cost-effectiveness studies and, in the Discussion (page not available), distinguishes its first-line analysis from studies of other treatment strategies. It reports that an earlier evaluation found add-on therapy cost-effective while its own first-line analysis did not, but it does not characterize the literature as conflicting or call for further studies with better economic modeling. (LLM, conf=0.76)
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- Authors
- Choi, J. G., Winn, A. N., Skandari, M. R., Franco, M. I., Staab, E. M., Alexander, J., Wan, W., Zhu, M., Huang, E. S., Philipson, L., & Laiteerapong, N.
- Affiliations
- University of Chicago (US)
- Medical College of Wisconsin (US)
- Imperial College London (GB)
- ORCID
- Venue
- Annals of Internal Medicine
- Publisher
- American College of Physicians
- Published
- 2022-10
- Volume
- 175
- Issue
- 10
- Pages
- 1392-1400
- ISSN
- 0003-4819 (ISSN-L)
- 1539-3704
- PMC
- PMC10155215
- OpenAlex
- W4300773139
- Cited by
- 87
- References
- 56
- Citations by year
- 2026: 16 · 2025: 21 · 2024: 21 · 2023: 27 · 2022: 2
- FWCI
- 13.15
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Annals of Internal Medicine (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (P30 DK092949)
- American Diabetes Association (1-18-JDF-037)
- National Institute on Aging (5T35 AG029795-13)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Social Sciences › Economics, Econometrics and Finance › Economics and Econometrics › Health Systems, Economic Evaluations, Quality of Life
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Failure Treatment and Management
- Keywords
- type 2 diabetes, SGLT2 inhibitors, GLP-1 receptor agonists, first-line therapy, cost-effectiveness, metformin, quality-adjusted life years, congestive heart failure, cardiovascular events, drug-naive patients, oral GLP-1 receptor agonists, lifetime costs, drug prices, health care costs, United States health care system
- MeSH terms
- Glucagon-Like Peptide-1 Receptor, Sodium-Glucose Transporter 2 Inhibitors, Cost-Benefit Analysis, Diabetes Mellitus, Type 2, Glucose, Humans, Hypoglycemic Agents, Metformin, Nutrition Surveys, Sodium, Quality-Adjusted Life Years, Sodium-Glucose Transporter 2, Glucagon-Like Peptide 1
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