A new research study revealed that six-month adjunct therapy with metformin does not improve glycemic control in overweight and obese teenagers with type 1 diabetes (T1D), despite showing a beneficial effect on cardiovascular risk factors such as reduced weight and body mass index (BMI). The clinical trial was developed by a partnership between T1D Exchange, whose goal is to find new and better therapies for T1D, and JDFR, the leading global organization funding T1D research. The study’s results were published in The Journal of the American Medical Association in a research article entitled “Effect of Metformin Added to Insulin on Glycemic Control Among Overweight/Obese Adolescents With Type 1 Diabetes”.
Metformin is an antidiabetic drug used in the treatment of type 2 diabetes patients, in particular obese or overweight, due to its ability to control blood sugar levels and improve resistance to insulin. Metformin has also shown potential benefits in T1D adult patients; however, previous studies assessing glycemic control in adolescents with T1D have been inconclusive regarding the drug’s effects.
In order to assess the efficacy and safety of metformin in treating overweight adolescents with type 1 diabetes, researchers conducted a placebo-controlled clinical trial with 140 adolescents (12 to 19 years old) with T1D for a mean duration of 7.0 years, from 26 pediatric endocrinology clinics. The enrolled adolescents were split into two groups receiving either the drug or the placebo for over 6 months. Follow-up visits were made at 6, 13 and 26 weeks. The primary outcome of the trial was change in HbA1c levels, a measure that refers to glycated hemoglobin and indicates the average blood sugar levels. Secondary outcomes included changes in total daily insulin, BMI, continuous glucose monitor indices, waist circumference, body composition, blood pressure, and lipids.
The results showed that, despite an initial reduction in HbA1c with metformin at the 13-week follow-up, there was no significant differences between the two groups at the 26th week. Despite the lack of lasting beneficial effect in glycemic control, the addition of metformin resulted in a 25% (at least) reduction of total daily insulin per kg of body weight in a larger proportion of the adolescents in the metformin group when compared to the placebo group (23% vs 1% of participants, respectively), 5% or greater reduction in weight in 17% of the metformin group and 7% of the placebo group, and reduced BMI by at least 10% in 24% of the patients receiving metformin and 7% of the placebo group participants. Despite these positive results in insulin sensitivity improvement and adiposity measures, metformin treatment resulted in an increased risk for gastrointestinal adverse events.
Researchers concluded that more research is needed to further confirm the positive effects of metformin on the cardiovascular risk of patients with T1D, and to determine the drug’s impact on diabetes complications in long-term treatment. Since metformin was not effective in controlling glycemia levels, insulin administration is still the only effective treatment option for T1D patients.
Sanjoy Dutta, PhD, assistant vice president of Translational Development at JDRF, commented on the study in a press release, “Repurposing available drugs is a very promising therapeutic avenue that JDRF is pursuing. While this initial study of metformin didn’t have the glycemic benefits we’d hoped for, JDRF and others are exploring its potential long-term cardiovascular benefits. The possibility of extending an available drug’s label indication would offer a speedy and affordable way to get new therapies into the hands of people with T1D when those drugs prove effective in clinical trials.”