Short-Term Intensive Insulin Therapy as a Remission Induction Strategy in Newly Diagnosed Type 2 Diabetes Mellitus: A Systematic Review.

Type 2 diabetes mellitus (T2DM) is characterized by progressive β-cell dysfunction, insulin resistance, and glucotoxicity, some of which may remain reversible early in the disease course. Short-term intensive insulin therapy (SIIT) may rapidly normalize hyperglycemia and facilitate β-cell recovery in newly diagnosed T2DM. This systematic review evaluated the effects of SIIT on glycemic control, drug-free remission, β-cell function, durability, and safety. PubMed/MEDLINE, Scopus, and Web of Science were searched for English-language randomized controlled trials published during the five-year period ending in April 2026. Four trials met the eligibility criteria. Because interventions, remission definitions, maintenance strategies, and follow-up periods differed substantially, study-level effect estimates, 95% confidence intervals, and p values were synthesized without statistical pooling. SIIT consistently improved early glycemic control, β-cell function, and insulin sensitivity. In one 245-participant trial, medication-supported hemoglobin A1c (HbA1c) below 6.5% at three months was achieved by 78.7% of participants receiving SIIT plus metformin-pioglitazone versus 59.0% receiving SIIT alone (adjusted p < 0.05); however, 12-month drug-free remission rates were similar at 50.0% and 50.6%, respectively (p = 0.972). Another trial found that linagliptin-metformin maintenance after SIIT increased the adjusted odds of achieving HbA1c below 7.0% at 48 weeks (odds ratio 2.78, 95% confidence interval 1.37-5.65; p = 0.005), although this represented medication-supported glycemic control rather than remission. In a two-year trial, induction SIIT improved β-cell function and insulin sensitivity (all p ≤ 0.0004), but repeated intermittent SIIT did not improve the Insulin Secretion-Sensitivity Index-2 (adjusted difference -35, 95% confidence interval -66 to -3; p = 0.03). Severe hypoglycemia was not reported in trials providing detailed safety data, and transient weight gain was not consistently demonstrated. SIIT may therefore serve as a selective metabolic induction strategy in early T2DM, but durable remission remains uncertain and may depend on effective sequential treatment. Standardized remission definitions, validated response predictors, and longer comparative trials are required before routine implementation.