Findings suggest that Metformin may help overcome pubertal insulin resistance and aid in better glycemic control.
The role of an insulin sensitizer such as metformin, with respect to glycemic control, in overweight or obese youth suffering from type 1 diabetes is unclear. Insulin resistance is one of the main reasons why this population of diabetics has poor glycemic control. Prior research has shown inconsistent results. Therefore, researchers set out to study the effects of metformin on hemoglobin A1c (HbA1c), total daily dose (TDD) of insulin, and other parameters in overweight or obese youth with T1DM.
The study conducted was a nine-month randomized, double blind, placebo controlled trial. There were 28 participants, 13 male and 15 female, aged between 10 to 20 years with HbA1c of >8%, BMI >85%, and diagnosed type-1 diabetes for more than 12 months. All subjects used a self-directed treat-to-target insulin regimen, which was titrated using an algorithm to adjust their long-acting insulin to achieve FPG between 90-120 mg/dL. It was important to have this uniform insulin treatment protocol, as previous studies have failed to account for this standardization among their patients. Participants of the study underwent a 3-month initial phase with the new insulin treatment regimen, and then received either 1,000 mg of metformin, or a placebo once daily for 9 months.
Over the course of the study, researchers found minor improvements that were clinically significant; however, did not reach statistical significance. A reduction in HbA1c of 0.4% was found in the treatment group compared to the placebo group (9.46% vs. 9.85%; P=0.903). A lower FPG was observed in the treatment group compared to placebo group (170.5 mg/dL vs. 189.4 mg/dL; P=0.927). A lower TDD of long acting insulin was also observed in the treatment group compared to placebo group (0.90 units/kg/day vs. 1.15 units/kg/day; P=0.221). Researchers also found that there was no difference in the occurrence of hypoglycemia between the groups.
The authors conclude that clinical significance was exhibited by the study; however, due to type-2 error associated with the small sample size, the study may not have been able to achieve statistical significance. Nonetheless, researchers claim that longer duration of treatment with addition of metformin could result in a clinically significant reduction in HbA1c in overweight or obese youth suffering from type-1 diabetes.
- The use of metformin as adjunctive therapy to an appropriate long-acting insulin regimen has shown a trend in reduction of HbA1c among overweight/obese youth with type-1 diabetes.
- While the results of this study displayed clinical significance in reduction of HbA1c, it did not show statistical significance.
- In order to achieve statistical significance, future studies with a larger sample size may be necessary so that results can be validated and generalized among this population of type-1 diabetics.
Nwosu B. U., et al “A randomized, double-blind, placebo controlled trial of adjunctive metformin therapy in overweight/obese youth with type 1 diabetes.” PLOS ONE (2015).