Use of Oral Metformin Therapy for Therapy-Induced Hyperglycemia in Pediatric Patients With Acute Lymphoblastic...

Hyperglycemia during treatment for pediatric acute lymphoblastic leukemia (ALL) is often induced by corticosteroids and asparaginase. Although insulin remains the standard therapy, oral metformin presents a promising alternative due to its ease of use, lower risk of hypoglycemia, and noninvasive route of administration-factors that can significantly enhance patient comfort and quality of life.

To evaluate the efficacy and safety of oral metformin in managing therapy-induced hyperglycemia (TIH) in children with ALL.

An ambispective analysis was conducted over 6 years (September 2018-August 2024) in pediatric ALL patients who developed hyperglycemia during induction or re-induction. We assessed the effectiveness of metformin in controlling hyperglycemia and the need for insulin in cases of suboptimal response.

Out of 281 ALL patients, 54 (19.2%) developed TIH, with a median age of 12 years (range 5-16). Most cases (57.4%, n = 31) occurred in the preadolescent/adolescent group. Pre-B ALL accounted for 85.2% (n = 46), and T-ALL for 14.8% (n = 8). A WBC count >20 × 10⁹/L was noted in 44.4% (n = 24). BMI was normal in 63% (n = 34), whereas 22.2% (n = 12) were overweight. Extremes of BMI (underweight/obese) were seen in 7.4% (n = 4) each. Most cases occurred during induction (49 patients), with 17 experiencing recurrence during re-induction. Hyperglycemia typically appeared within a week of initiating steroids. The mean baseline glucose was 240 mg/dL (range: 201-338 mg/dL), which declined to 137 mg/dL at Day 7 (range: 110-174 mg/dL), with a mean reduction from baseline of 103 mg/dL. Metformin (up to 1500 mg/day) successfully controlled blood glucose in 36 induction-phase patients (73.4%, 95% CI 59.7-83.8), whereas 13 (26.5%) required insulin. During re-induction, seven patients needed dual therapy. Insulin was added for glucose >300 mg/dL, signs of ketoacidosis, or poor response to metformin. In the TIH group, febrile neutropenia and culture-positive sepsis occurred in 42.6% (n = 23) and 24.1% (n = 13), respectively-higher than in non-hyperglycemic patients. All patients reverted to euglycemia after steroid tapering, with no long-term hypoglycemic therapy needed. Metformin was well-tolerated, with no adverse effects warranting discontinuation. Glycemic management did not interfere with leukemia remission or treatment completion.

Oral metformin proved to be a safe and effective first-line option for managing TIH in pediatric ALL. Insulin therapy could be avoided in majority of the patients (73.4% in induction, 68.1% in re-induction), making this drug an attractive first-line option for children with treatment-induced non-severe hyperglycemia.