December 02, 2015
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Metformin fails to improve HbA1c in adolescents with type 1 diabetes, overweight

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Adolescents with type 1 diabetes and overweight or obesity did not see an improvement in their HbA1c levels after 26 weeks of metformin therapy vs. those randomly assigned a placebo, although less weight gain occurred in the metformin group, according to research in JAMA.

Ingrid M. Libman, MD, PhD, associate professor in the division of pediatric endocrinology and diabetes at Children’s Hospital of Pittsburgh of UPMC, and colleagues analyzed data from 140 adolescents aged 12.1 to 19.6 years with type 1 diabetes and either overweight or obesity who visited the T1D Exchange Clinic Network (mean age, 15.3 years; mean diabetes duration, 7 years; 66% girls; 75% white). Within the cohort, the mean HbA1c was 8.8%; mean BMI z score was 1.6; mean total daily insulin was 1.1 U/kg per day. Researchers randomly assigned participants daily metformin therapy in addition to basil-bolus insulin therapy (n = 71) or placebo plus insulin therapy (n = 69) for 6 months. Metformin doses were gradually increased from one tablet daily for 7 days to two tablets in the morning and two tablets in the evening (2,000 mg); participants visited clinics at 6, 13 and 26 weeks, and 4 to 6 weeks after the study concluded, and wore a blinded continuous glucose monitor for 3 to 7 days at baseline, 13 and 26 weeks.

After 13 weeks, participants in the metformin group saw a slightly greater decrease in HbA1c vs. placebo (–0.2% vs. 0.1%; P = .02); however, the difference was not apparent at 26 weeks, when both groups saw a mean 0.2% increase. Continuous glucose monitoring and subsequent sensitivity analyses showed no significant treatment group differences for the change in HbA1c, according to researchers.

Total daily insulin dose fell by 25% or more for 16 participants in the metformin group after 26 weeks vs. just one participant in the placebo group (P = .003), and fewer participants in the metformin group experienced weight gain of 5% or more during the study period (24% vs. 41%; P = .04). Researchers observed no significant between-group differences for blood pressure, lipid levels, C-reactive protein or C-peptide. Three participants in the metformin group experienced diabetic ketoacidosis vs. two participants assigned placebo; five metformin participants experienced severe hypoglycemia vs. no cases in the placebo group. Gastrointestinal adverse events were more common in the metformin group vs. placebo (80% vs. 57%; P = .003).

“The lack of benefit on glycemic control at 6 months is unlikely [the result of] bias because study completion was nearly 100%, the treatment discontinuation rate was low, and blinding of treatment assignment was maintained” the researchers wrote. “It does not seem likely that different glycemic control results would have been achieved with a longer treatment period.”

The researchers noted that although observed changes in body weight composition and daily insulin requirements may have improved insulin sensitivity, there were no concomitant improvements in cardiovascular risk factors. – by Regina Schaffer

Disclosure: Libman reports receipt of a grant from the JDRF and of grants to the institution from Novo Nordisk. Please see the full study for the other authors’ relevant financial disclosures.