How beneficial is the addition of metformin to insulin therapy for adolescents with type 1 diabetes?

This study assessed the effectiveness and safety of adding metformin (Glucophage) to insulin therapy in the treatment of adolescents with type 1 diabetes (T1D). The study showed that the use of metformin in these patients resulted in improved blood glucose control and body mass index (BMI) with an increased risk of hypoglycemia (dangerously low blood glucose) and gastrointestinal side effects (GISE).

T1D is the most common form of diabetes occurring in children and adolescents. The inability of the pancreas to produce the hormone insulin results in high blood glucose (sugar) levels. Insulin therapy is typically the standard of care for these patients. However, therapeutic goals are not always met. Additionally, considerable weight gain associated with insulin therapy can increase the risk of heart disease.

Metformin is a drug that has been used to control blood glucose levels in patients with type 2 diabetes (T2D). Metformin decreases glucose production by the liver and assists with its uptake into muscles, improving the sensitivity of tissues to insulin. Metformin has been shown to improve patient outcomes for heart-related complications.

Based on this, metformin is currently under investigation for potential use in T1D. Although previous analyses have investigated the effect and safety of adding metformin to insulin therapy in adolescents with T1D, definitive conclusions were not reached. There is a need for an updated, comprehensive analysis of available study results.

This analysis included 10 studies with 539 adolescents with T1D. 4 studies involved obese or overweight adolescents. 6 studies included general adolescents. Patients received either metformin or a placebo in addition to insulin therapy. Metformin daily doses ranged from 500 mg to 2000 mg. Glycated hemoglobin (HbA1c; a measure of blood glucose control over the past 2-3 months) levels, BMI (a measure of weight in relation to height), total insulin daily dose (TIDD), and side effects were evaluated. Duration of treatment ranged from 3 months to 12 months.

At 12 months, a significant decrease in the HbA1c level was observed in the metformin group compared to placebo. At 6 months, BMI was significantly reduced in the metformin group. The TIDD was significantly decreased in the metformin group at 3, 6, and 12 months.

There was a significantly higher risk of developing very low blood glucose levels and digestive side effects with the addition of metformin to insulin treatment.

The study concluded that the addition of metformin to insulin therapy in adolescents with T1D may decrease HbA1c levels, BMI, and TIDD but can increase the risk of very low blood glucose levels and side effects related to the digestive tract.

This analysis included many studies with very small patient numbers which may result in an overestimation of the therapeutic effect.