Introduction and background

Type 2 diabetes mellitus (T2DM) is a progressive metabolic disorder characterized by varying degrees of insulin resistance, impaired insulin secretion, and progressive β-cell dysfunction [1]. Although conventional treatment strategies have traditionally emphasized stepwise pharmacologic intensification beginning with oral antihyperglycemic agents, increasing attention has been directed toward the potential reversibility of early metabolic dysfunction during the initial stages of disease development. Chronic hyperglycemia contributes to glucotoxic stress, oxidative injury, impaired first-phase insulin secretion, and worsening hepatic insulin resistance, all of which may accelerate β-cell exhaustion over time [2]. Evidence from experimental and clinical studies suggests that a proportion of β-cell dysfunction in newly diagnosed T2DM may remain functionally reversible if metabolic stress is rapidly corrected before irreversible cellular decline becomes established [3].

Short-term intensive insulin therapy (SIIT), commonly delivered through continuous subcutaneous insulin infusion (CSII) or multiple daily injection protocols, has emerged as a potential strategy for achieving rapid glycemic normalization in patients with newly diagnosed T2DM, particularly those presenting with severe hyperglycemia [4]. Beyond its immediate glucose-lowering effects, SIIT has been proposed to reduce glucotoxic burden, improve insulin sensitivity, and temporarily “unload” pancreatic β-cells, thereby facilitating partial restoration of endogenous insulin secretory capacity. Several randomized studies have demonstrated improvements in glycemic control, β-cell function indices, and short-term remission rates following SIIT-based interventions [5]. However, the extent to which these metabolic improvements translate into sustained long-term remission remains uncertain, with variability observed across patient populations, maintenance therapies, and follow-up durations.

More recently, the concept of remission-oriented diabetes management has gained increasing clinical and scientific interest, shifting attention toward early disease modification rather than exclusive long-term pharmacologic escalation. Within this framework, SIIT has been explored not only as a temporary glucose-lowering intervention but also as a potential metabolic induction strategy during periods of marked but potentially reversible glucotoxicity [6,7]. Nevertheless, important uncertainties remain regarding optimal patient selection, remission durability, maintenance treatment requirements, and the relationship between early β-cell recovery and long-term disease trajectory. In addition, heterogeneity in remission definitions and post-induction therapeutic strategies has complicated direct comparisons across studies [8].

Previous reviews have suggested that SIIT may improve glycemic control and β-cell function in newly diagnosed T2DM; however, much of this evidence predates recently published randomized controlled trials evaluating newer induction and post-induction treatment strategies. Important uncertainties also remain regarding the durability of remission, the contribution of maintenance pharmacotherapy, and the clinical characteristics associated with sustained response. An updated synthesis is therefore needed to integrate these recent trials and clarify whether early metabolic improvements translate into durable remission. Accordingly, this systematic review aims to evaluate the effects of SIIT on glycemic remission, β-cell functional recovery, and metabolic outcomes in adults with newly diagnosed or early T2DM. It further examines remission durability and synthesizes current evidence regarding the potential role of SIIT as a phenotype-directed induction strategy in early T2DM management.