Should the last be first? Questions and dilemmas regarding early short-term insulin treatment in Type 2 Diabetes Mellitus

ABSTRACT

Introduction: Early short-term insulin treatment (STIT), defined as insulin administration shortly after diabetes diagnosis for only a brief period of time, is an alternative concept, aiming to entirely revise the perspective of type 2 diabetes (T2DM) management.

Areas covered: The present review intends to summarize what is already known regarding early STIT in T2DM and highlight questions and dilemmas from the clinician’s point of view, with a discourse on future research agenda.

Expert opinion: STIT has the potential to modify the natural history of T2DM, resulting in improved drug-free remission rates by favorably affecting the underlying pathophysiology of the disease. Existing data in the field manifest significant weaknesses, mainly being the small number of trials and patients included, the lack of control groups in most studies and the wide heterogeneity between study designs and explored outcomes, which limit definitive conclusions. Therefore, before such a therapeutic strategy is incorporated into daily practice, important issues require further clarification by future trials. These issues include the optimal time point for the intervention, the ideal insulin type, the identification of patients being most likely to benefit, the STIT effects on cardiovascular and other clinical outcomes and the cost-effectiveness evaluation of this therapeutic strategy.

Abbreviations: T2DM: Type 2 Diabetes Mellitus; HbA_1C: Hemoglobin A_1c; OHA: Oral Hypoglycemic Agents; STIT: Short-term Insulin Treatment; CSII: Continuous Subcutaneous Insulin Infusion; MDI: Multiple Daily Injections; PPG: Postprandial Plasma Glucose; FPG: Fasting Plasma Glucose; HOMA-b: Homeostasis Model Assessment of beta-cell function; TDD: Total Daily Insulin Dose; DI: Disposition Index; HOMA-IR: Homeostasis Model Assessment of Insulin Resistance; ROS: Reactive Oxygen Species; TNF: Tumor Necrosis Factor; GLP-1: Glucagon-like peptide-1; GIP: Glucose-dependent Insulinotropic Polypeptide; BMI: Body Mass Index; CV: Cardiovascular; DR: Diabetic Retinopathy; SU: Sulfonylurea; IGI: Insulinogenic Index

KEYWORDS:

• Beta-cell
• glucotoxicity
• insulin
• pleiotropic actions
• type 2 diabetes mellitus

Article highlights

• Insulin is often considered as the last treatment option in T2DM

• Early short-term insulin treatment (STIT) results in improved remission rates by favorably affecting T2DM pathophysiology

• These optimal effects on glucose homeostasis are facilitated by the pleiotropic actions of insulin

• Specific issues regarding STIT require further clarification by future trials

This box summarizes key points contained in the article.

Declaration of Interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

This manuscript is not funded.