What is the role of long-acting insulin (LAI) as a first-line therapy in children with type 2 diabetes mellitus (T2DM)?

From the Guidelines

Long-acting insulin (LAI) is not recommended as first-line therapy for children with type 2 diabetes mellitus (T2DM). The current first-line treatment for pediatric T2DM is metformin, often combined with lifestyle modifications including dietary changes and increased physical activity, as supported by the most recent guidelines 1. Insulin therapy, including LAI such as insulin glargine, insulin detemir, or insulin degludec, is typically reserved for specific situations: when the initial presentation includes severe hyperglycemia (blood glucose >250 mg/dL), ketosis or ketoacidosis, or when the distinction between type 1 and type 2 diabetes is unclear. LAI may also be considered when metformin is contraindicated or not tolerated, or when glycemic targets are not achieved with metformin monotherapy.

Key Considerations

• The pathophysiology of pediatric T2DM initially involves insulin resistance rather than absolute insulin deficiency, making metformin a more appropriate first-line treatment 1.
• Metformin offers advantages of weight neutrality and lower hypoglycemia risk compared to insulin therapy, which are particularly important considerations in the pediatric population 1.
• When insulin is needed, the starting dose is usually calculated based on weight (0.5-1 units/kg/day), with adjustments made according to blood glucose monitoring results 1.
• Glycemic goals should be individualized, taking into consideration the long-term health benefits of more stringent goals and risk for adverse effects, such as hypoglycemia 1.

Recommendations

• Initiate pharmacologic therapy, in addition to behavioral counseling for healthful nutrition and physical activity changes, at diagnosis of type 2 diabetes 1.
• In individuals with incidentally diagnosed or metabolically stable diabetes (A1C <8.5% [69 mmol/mol] and asymptomatic), metformin is the initial pharmacologic treatment choice if kidney function is normal 1.
• Consider maximizing noninsulin therapies (metformin, a GLP-1 receptor agonist, and empagliflozin) before initiating and/or intensifying insulin therapy plan 1.

From the FDA Drug Label

Insulin Glargine is a long-acting human insulin analog indicated to improve glycemic control in adult and pediatric patients with diabetes mellitus. (1) Limitations of Use Not recommended for the treatment of diabetic ketoacidosis. (1)

The role of long-acting insulin (LAI) as a first-line therapy in children with type 2 diabetes mellitus (T2DM) is not explicitly stated in the provided drug labels. However, it is indicated that Insulin Glargine is used to improve glycemic control in pediatric patients with diabetes mellitus 2.

• The labels do not provide information on the use of LAI as a first-line therapy in children with T2DM.
• The dosage and administration section of the label provides guidance on individualizing dosage based on metabolic needs, blood glucose monitoring, glycemic control, type of diabetes, and prior insulin use 2.
• Key considerations for the use of Insulin Glargine in pediatric patients include closely monitoring glucose when switching to Insulin Glargine and during initial weeks thereafter, as well as rotating injection sites to reduce the risk of lipodystrophy and localized cutaneous amyloidosis 2.

From the Research

Role of Long-Acting Insulin in Type 2 Diabetes in Children

The use of long-acting insulin (LAI) as a first-line therapy in children with type 2 diabetes mellitus (T2DM) is a topic of interest due to the increasing prevalence of T2DM in pediatric populations.

• Indications for Insulin Therapy: According to 3, indications for exogenous insulin therapy in patients with T2DM include acute illness or surgery, pregnancy, glucose toxicity, contraindications to or failure to achieve goals with oral antidiabetic medications, and a need for flexible therapy.
• Preferred Method of Insulin Initiation: The preferred method of insulin initiation in T2DM is to begin by adding a long-acting (basal) insulin or once-daily premixed/co-formulation insulin or twice-daily premixed insulin, alone or in combination with glucagon-like peptide-1 receptor agonist (GLP-1 RA) or in combination with other oral antidiabetic drugs (OADs) 3.
• GLP-1 Receptor Agonists: GLP-1 receptor agonists, such as exenatide and liraglutide, have been shown to be effective in reducing glycated hemoglobin (A1C) and weight loss in patients with T2DM, with a low risk of hypoglycemia 4.
• Insulin Therapy in Children and Adolescents: While there is limited evidence on the use of LAI as a first-line therapy in children with T2DM, studies on type 1 diabetes mellitus (T1DM) suggest that basal-bolus therapy with multiple daily injections (MDI) or continuous subcutaneous insulin infusion (CSII) can be effective in achieving target glycemic control 5, 6.
• Second-Line Therapy: For patients failing on metformin, GLP-1/DPP-IV inhibitors may be considered as a second-line therapy, with potential benefits including glucose-dependent insulin secretion, glucagon suppression, and minimal hypoglycemia 7.

Overall, while there is limited direct evidence on the use of LAI as a first-line therapy in children with T2DM, the available evidence suggests that insulin therapy, including LAI, can be an effective treatment option for achieving glycemic control in pediatric patients with T2DM.