Abstract
Type 2 diabetes mellitus (T2DM) is a global health priority, with an estimated 629 million people projected to be affected by the year 2045. T2DM significantly increases the risk of atherosclerotic cardiovascular disease and other complications. Hyperglycaemia imprints early molecular and cellular changes, often termed "metabolic memory", predisposing individuals to long-term microvascular and macrovascular complications, even after glycaemic normalisation. T2DM remission is increasingly recognised as an achievable target, offering substantial benefits such as reduced morbidity, improved quality of life, and preservation of beta-cell function. Among therapeutic options, metabolic surgery (MS) demonstrates the most significant impact, particularly for long-term outcomes. MS induces profound hormonal changes, including increased glucagon-like peptide 1 (GLP-1) levels and improved bile acid metabolism, alongside reductions in ectopic fat in the liver and pancreas, which improve insulin sensitivity and secretion. However, intensive lifestyle and pharmacological interventions, such as GLP-1 receptor agonists and glucose-dependent insulinotropic polypeptide/glucagon-like peptide 1 dual agonists like tirzepatide, also show promise, particularly when implemented early in the disease course. Predictors of sustained remission include younger age, shorter diabetes duration, lower baseline HbA1c, absence of insulin use, fewer medications and greater total weight loss percentage. Emerging tools such as the DiaRem score, machine learning models, and biomarkers like FGF-21 enhance patient stratification and predict remission likelihood. This narrative review explores the mechanisms and therapeutic options for T2DM remission, evaluates their impact on long-term outcomes and highlights the importance of early, multidisciplinary, and personalised interventions to optimize remission and improve metabolic health.
Authors
Corrao, Salvatore; Falcone, Fabio; Mirarchi, Luigi; Amodeo, Simona; Calvo, Luigi