Intermittent Intensive Insulin Therapy for Type 2 Diabetes: Effects on Hypoglycemia, Weight Gain, and Quality of Life Over 2 Years

Abstract

Objective: In early type 2 diabetes (T2DM), the administration of short-term intensive insulin therapy (IIT) can induce glycemic remission for a year thereafter, but this effect ultimately wanes. In this context, intermittently repeating short-term IIT could provide a strategy for maintaining the otherwise transient benefits of this intervention. However, the viability of this strategy would be contingent upon not inducing undesirable effects of insulin therapy such as excessive hypoglycemia and fat deposition. We thus sought to evaluate the effect of administering short-term IIT every 3 months on hypoglycemia, weight gain, and quality of life in early T2DM. Methods: In this 2-year pilot trial, 24 adults with T2DM of 2.0 ± 1.7 years duration and hemoglobin A1c of 6.4 (46 mmol/mol) ± 0.1% were randomized to 3 weeks of IIT (glargine, lispro) followed by either (1), repeat IIT for up to 2 weeks every 3 months or (2), daily metformin. IIT was titrated to target near-normoglycemia (premeal glucose 4 to 6 mmol/L; 2-hour postmeal <8 mmol/L). Participants were assessed every 3 months, with quality of life (QOL) evaluated annually. Results: The rate of hypoglycemia (<3.5 mmol/L) was low in the metformin and intermittent IIT arms (0.37 versus 0.95 events per patient-year; P = .28). There were no differences between the groups in changes over time in overall, central, or hepatic fat deposition (as reflected by weight [P = .10], waist-to-hip ratio [P = .58], and alanine aminotransferase [P = .64], respectively). Moreover, there were no differences between the groups in QOL at 1- and 2-years. Conclusion: Intermittent short-term IIT may be safely administered in early T2DM without excessive adverse impact on hypoglycemic risk, anthropometry, or QOL. Abbreviations: ALT = alanine aminotransferase; HbA1c = hemoglobin A1c; IIT = intensive insulin therapy; ISSI-2 = insulin secretion-sensitivity index-2; OGTT = oral glucose tolerance test; QOL = quality of life; SF-36 = medical outcomes study 36-item short-form health survey; T2DM = type 2 diabetes.