Background and Objective <p>The rising global burden of type 2 diabetes mellitus, compounded by the expanding therapeutic landscape, has placed increasing pressure on health systems to generate robust evidence on the long-term value for money of newer antidiabetic drugs (NADs). This systematic review addresses the urgent need for an updated synthesis of evidence on long-term health economic evaluations of NADs for the treatment of type 2 diabetes, including studies on the latest agents such as tirzepatide and finerenone. It aims to synthesise global long-term cost-effectiveness analyses, assess reporting completeness using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) 2022 framework and outline key implications for clinicians, payers and policymakers seeking to optimise type 2 diabetes management within resource-constrained health systems.</p> Methods <p>PubMed, Embase, Cochrane, EBSCOhost, Scopus and Web of Science were systematically searched for studies published between 1 January, 2008 and 20 February, 2025. Eligible studies were long-term incremental cost-effectiveness analyses conducted in adults with type 2 diabetes, comparing NADs with other NAD classes or with standard treatment, and reporting outcomes such as incremental cost-effectiveness ratios. A formal risk of bias assessment using tools designed for clinical trials was not undertaken. Instead, reporting quality and transparency were assessed using the CHEERS 2022 checklist, with modelling-related sources of uncertainty and potential bias examined qualitatively. Given the methodological heterogeneity, results were synthesised narratively. Full-text English articles were included. This review was not prospectively registered.</p> Results <p>The search identified 1481 records, of which 142 studies met the inclusion criteria. Overall, 81% of incremental cost-effectiveness ratio-based analyses reported that NADs were cost effective compared with conventional therapies under country-specific willingness-to-pay thresholds. Using Thailand as an example of a developing country, studies generally found NADs not to be cost effective, largely because willingness-to-pay thresholds (USD 4336–5310 per quality-adjusted life-year) are substantially lower than those in higher income settings. Recently introduced agents (e.g. tirzepatide and finerenone) and early-line use were typically cost effective only at higher willingness-to-pay thresholds (USD 100,000–150,000 per quality-adjusted life-year) or following substantial price reductions (≥&#xa0;70% for sodium glucose cotransporter-2 inhibitors and ≥90% for oral glucagon-like peptide-1 receptor agonists). Most evaluations employed established diabetes models and adopted lifetime horizons from a payer perspective, while reporting quality assessments revealed limited disclosure of stakeholder involvement.</p> Conclusions <p>These findings should be interpreted cautiously given the substantial heterogeneity across studies and methodological limitations inherent to long-term economic modelling. Overall, NADs generally provide favourable long-term cost effectiveness, owing to their cardiovascular and renal benefits; however, recently introduced agents and early-line use tend to be cost effective only at higher willingness-to-pay thresholds or after significant price reductions. Future evaluations should integrate real-world evidence and advanced modelling to capture long-term impacts and incorporate context-specific affordability considerations to support equitable and sustainable adoption of newer antidiabetic therapies.</p>