Complication Prevention Beyond Glycaemic Control in Type 2 Diabetes: Cumulative Metabolic Exposure, Organ Vulnerability and Treatment Durability
Endocrinology, Diabetes & Metabolism · 2026-11 · 9 (6)
DOI: 10.1002/edm2.70383 ↗Rezumat
ABSTRACT Introduction Type 2 diabetes is a progressive multisystem disorder in which long‐term complication burden reflects more than contemporaneous glycaemic control. Age at onset, previous metabolic exposure, obesity‐related risk, organ injury, treatment safety and the capacity to sustain effective care interact across the disease course. Methods This critical narrative review synthesised targeted PubMed/MEDLINE searches, international guidance, landmark and contemporary randomised trials, longitudinal cohorts, validated risk models and clinically influential reviews. A targeted update search was completed through 22 September 2026. Results The evidence supports a clinically ordered approach in which immediate treatment‐related hazards are considered first, followed by established organ disease or a dominant preventable outcome, residual modifiable cardiometabolic exposure, treatment durability and the care systems required to translate evidence into sustained benefit. Historical trials established the importance of glycaemic, blood‐pressure and lipid management and coordinated multifactorial intervention. Contemporary SGLT2 inhibitor and incretin‐based trials add direct cardiovascular, heart‐failure and kidney outcome evidence in defined populations, while MASH trials provide emerging histological evidence. HbA1c, validated risk equations and organ‐specific pathways retain their established roles. Conclusions The proposed framework is interpretive rather than predictive. It does not assign numerical weights or treatment thresholds but aims to identify the preventable outcome that should take priority, the intervention supported by the most relevant evidence and whether that intervention can be implemented safely and durably.
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