What is the most appropriate treatment for a 17-year-old male with type 2 diabetes mellitus (T2DM), presenting with hyperglycemia, polyuria, polydipsia, and significant weight loss, after discontinuing metformin (Metformin) therapy 6 months prior?

From the Guidelines

The most appropriate treatment for this 17-year-old male with poorly controlled type 2 diabetes would be starting subcutaneous insulin, specifically long-acting insulin, while metformin is initiated and titrated. This patient presents with significant hyperglycemia, markedly elevated HbA1c, and symptoms of uncontrolled diabetes including polyuria, polydipsia, weight loss, and fatigue. While he previously took metformin, his current clinical presentation indicates severe decompensation requiring more aggressive therapy. Insulin is the preferred treatment in this scenario because it provides rapid and effective glucose control needed for someone with such profound hyperglycemia and symptoms, as recommended by the most recent guidelines 1.

Key Considerations

• The patient's significant hyperglycemia and symptoms of uncontrolled diabetes necessitate immediate and effective glucose control, which can be achieved with insulin therapy.
• Metformin alone would be insufficient given the severity of his presentation, but it can be initiated and titrated in conjunction with insulin therapy.
• The use of long-acting insulin is recommended for youth with marked hyperglycemia without acidosis at diagnosis who are symptomatic, as stated in the 2023 standards of care in diabetes 1.
• After stabilization with insulin, the patient would benefit from diabetes education, regular monitoring, and potentially adding oral agents as adjunctive therapy once glucose levels are better controlled.

Treatment Approach

• Initiate long-acting insulin while metformin is initiated and titrated, as recommended by the 2023 guidelines 1.
• Monitor the patient's glucose levels closely and adjust the insulin dose as needed to achieve glycemic targets.
• Consider adding oral agents, such as metformin, as adjunctive therapy once glucose levels are better controlled, but prioritize insulin therapy for immediate glucose control.

From the FDA Drug Label

The mean age of the trial population was 56.6 years and mean duration of diabetes was 12. 7 years. Sixty-three percent were male. Seventy-six percent were Caucasian, 9% were Black and 15% were Other. The mean BMI was approximately 29. 7 kg/m2. Insulin Aspart was administered by subcutaneous injection immediately prior to meals and regular human insulin was administered by subcutaneous injection 30 minutes before meals. NPH insulin was administered as the basal insulin in either single or divided daily doses. Changes in HbA1c were comparable for the two treatment regimens.

Table 5 Subcutaneous Insulin Aspart Administration in Type 2 Diabetes (6 months; n=176) Insulin Aspart + NPH (n=90) Regular Human Insulin + NPH (n=86) Baseline HbA1c (%)* 8.1 ± 1.2 7.8 ± 1.1 Change from Baseline HbA1c (%) -0.3 ± 1.0 -0.1 ± 0.8 Treatment Difference in HbA1c, Mean (95% confidence interval) - 0.1 (-0.4,0.1)

The most appropriate treatment for a 17-year-old male with Type 2 Diabetes Mellitus (T2DM), presenting with hyperglycemia, polyuria, polydipsia, and significant weight loss, after discontinuing metformin therapy 6 months prior, is not directly addressed in the provided drug label. However, based on the available information, insulin aspart can be considered as a treatment option for Type 2 Diabetes.

• Key points:
  • The drug label provides information on the efficacy of insulin aspart in adults with Type 2 Diabetes.
  • The study results show that insulin aspart can be effective in improving glycemic control in adults with Type 2 Diabetes.
  • However, the drug label does not provide specific information on the treatment of Type 2 Diabetes in pediatric patients, particularly those who have discontinued metformin therapy.
• Clinical decision: Considering the patient's age and diagnosis of Type 2 Diabetes, insulin aspart may be considered as a treatment option, but it is essential to consult the patient's healthcare provider to determine the best course of treatment, as the drug label does not provide direct guidance on this specific scenario 2.

From the Research

Treatment Options for Type 2 Diabetes Mellitus (T2DM)

The patient in question is a 17-year-old male with T2DM, presenting with hyperglycemia, polyuria, polydipsia, and significant weight loss, after discontinuing metformin therapy 6 months prior. Considering his condition, the following treatment options can be explored:

• Insulin therapy is considered alone or in combination with oral agents when HbA1c is ≥ 7.5% (≥ 58 mmol/mol) 3.
• 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.
• If the desired glucose targets are not met, rapid-acting or short-acting (bolus or prandial) insulin can be added at mealtime to control the expected postprandial raise in glucose 3.

Insulin Regimens

The following insulin regimens can be considered for the patient:

• Basal-bolus insulin strategy, which resulted in better glycemic control than sliding scale insulin and lower risk of hypoglycemia than premixed insulin regimen 4, 5.
• Continuous intravenous insulin infusion, which is the best method for achieving glycemic targets in critically ill patients, but may not be necessary for this patient 4, 5.
• Scheduled subcutaneous (SC) basal-bolus insulin regimens supplemented with correction doses as needed and adjusted daily with the guidance of frequent blood glucose monitoring 5.

Glycemic Targets

The target glycated hemoglobin A1c (HbA1c) for patients with T2DM is recommended to be < 7.5% (< 58 mmol/mol) 3.

• Target glucose range of 110-180 mg/dL may be appropriate for most patients, with glucose targets near 140 mg/dL recommended as being the most appropriate for all patients 4, 5.

Insulin Types

The following types of insulin can be considered for the patient:

• Long-acting basal insulin analogs (glargine, detemir) are suitable and preferred for the basal component of therapy 5, 6.
• Rapid-acting insulin analogs (aspart, lispro, glulisine) are recommended for bolus and correction doses 5, 6, 7.
• Insulin degludec is an ultra-long-acting insulin analogue with a flat and stable glucose-lowering profile, and can be used in combination with prandial insulin aspart (insulin degludec/insulin aspart) 6.