A Systematic Review of Cost-Effectiveness Studies of Newer Non-Insulin Antidiabetic Drugs: Trends in Decision-Analytical Models for Modelling of Type 2 Diabetes Mellitus

Background We performed a systematic overview of the cost-effectiveness analyses (CEAs) comparing Non-insulin antidiabetic drugs (NIADs) with other NIADs for the treatment of type 2 diabetes mellitus (T2DM), using decision-analytical modelling (DAM), focusing on both the economic results and the underlying methodological choices. Methods Eligible studies were CEAs using DAM to compare NIADs within the glucagon-like peptide-1 (GLP1) receptor agonists, sodium-glucose cotransporter-2 (SGLT2) inhibitors, or dipeptidyl peptidase-4 (DPP4) inhibitor classes with other NIADs within those classes for the treatment of T2DM. The PubMed, Embase and Econlit databases were searched from 1 January 2018 to 15 November 2022. Two reviewers screened the studies for relevance by titles and abstracts and then for eligibility via full-text screening, extracted the data from the full texts and appendices, and then stored the data in a spreadsheet. Results The search yielded 890 records and 50 studies were eligible for inclusion. The studies were mainly based on a European setting (60%). Industry sponsorship was found in 82% of studies. The CORE diabetes model was used in 48% of the studies. GLP1 and SGLT2 products were the main comparators in 31 and 16 studies, respectively, while one study had DPP4 and two had no easily discernible main comparator. Direct comparison between SGLT2 and GLP1 occurred in 19 studies. At a class level, SGLT2 dominated GLP1 in six studies and was cost effective against GLP1 once as part of a treatment pathway. GLP1 was cost effective in nine studies and not cost effective against SGLT2 in three studies. At a product level, oral and injectable semaglutide, and empagliflozin, were cost effective against other within-class products. Injectable and oral semaglutide were more frequently found cost effective in these comparisons, with some conflicting results. Most of the modelled cohorts and treatment effects were sourced from randomised controlled trials. The following model assumptions varied depending on the class of the main comparator: choice of and reasoning behind risk equations, the time until the treatment switch, and how often the comparators were discontinued. Diabetes-related complications were emphasised on par with quality-adjusted life-years as model outputs. The main quality issues were regarding the description of alternatives, the perspective of analysis, the measurement of costs and consequences, and patient subgroups. Conclusion The included CEAs using DAMs have limitations that hinder their ability to inform decision makers on the cost-effective choice: lack of updated reasoning behind the choice of key model assumptions, over-reliance on risk equations based on older treatment practices, and sponsorship bias. The question of which NIAD is cost effective for the treatment of which T2DM patient is a pressing one and the answer remains unclear.