Adding Metformin to Insulin Did Not Improve Glycemic Control in Adolescents with Type 1 Diabetes

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Adolescents with type 1 diabetes did not experience improved glycemic control with metformin.
Adolescents with type 1 diabetes did not experience improved glycemic control with metformin.

Adding metformin to insulin therapy did not improve glycemic control in overweight adolescents with type 1 diabetes after 6 months, new research published in the Journal of the American Medical Association suggests.

Approximately 24% of adolescents in the United States with type 1 diabetes are overweight, and an additional 15% are obese. Adolescents with type 1 diabetes who are overweight are at increased risk for developing metabolic problems, and as a result, these individuals must take higher doses of insulin to overcome the insulin resistance associated with obesity and puberty, according to background information in the study.

Metformin, a drug commonly used to lower glucose in type 2 diabetes, has been tested in adolescents with type 1 diabetes to improve glycemic control, but results have been inconclusive, the researchers noted.

Kellee Miller, PhD, of the Jaeb Center for the Health Research in Tampa, Florida, and colleagues conducted a multicenter, double-blind trial that included 140 adolescents with type 1 diabetes aged 12.1 to 19.6 years. The participants were randomly assigned to receive metformin (n=71) or placebo (n=69). The participants received increasing daily doses of metformin or placebo for 26 weeks.

Mean BMI z score was 1.6, mean HbA1c was 8.8%, and mean total daily insulin 1.1 U/kg per day.

After 13 weeks, the researchers saw a reduction of –0.2% in HbA1c in the metformin group vs 0.1% in the placebo group.  But at 26 weeks, the average change in HbA1c was 0.2% for both groups.

At 26 weeks, the total daily insulin per kg of body weight was reduced by 25% in 16 of the patients in the metformin group vs 1 patient in the placebo group.

Seventeen of the patients in the metformin group and 5 in the placebo group also experienced an at least 10% reduction in BMI z score at 26 weeks.

More patients in the metformin group reported gastrointestinal adverse events than in the placebo group, according to the data.

“Of multiple secondary end points, findings favored metformin only for insulin dose and measures of adiposity; conversely, metformin resulted in an increased risk for gastrointestinal adverse events,” the researchers concluded. “These results do not support prescribing metformin to adolescents to improve glycemic control.”

The researchers noted that it is unlikely that metformin could improve glycemic control with a longer period of treatment. The metformin group did experience a reduction in weight gain, BMI, body fat, and total daily insulin dose, but the clinical implications of the differences between treatment groups is unknown.

Reference

  1. Libman IM, Miller KM, DiMeglio LA, et al; for the T1D Exchange Clinic Network Metformin RCT Study Group. Effect of Metformin Added to Insulin on Glycemic Control Among Overweight/Obese Adolescents With Type 1 Diabetes: A Randomized Clinical Trial. JAMA. 2015;314(21):2241-2250.
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