Six-Month Clinical Trial Reveals Addition of Metformin Fails to Improve Glycemic Control in Adolescents Living with Type 1 Diabetes

BOSTON, Dec. 1, 2015 /PRNewswire/ -- Six months of adjunctive metformin therapy does not improve glycemic outcomes in overweight adolescents with type 1 diabetes, according to new research from T1D Exchange and funded by the JDRF. However, it may have a beneficial effect on measures of obesity, including weight and BMI. The results, published in the current issue of the Journal of the American Medical Association, are from the largest clinical trial to date examining the effect of metformin on overweight and obese adolescents with type 1 diabetes.

Though the body mass composition of type 1 patients has traditionally been normal or underweight, recent data from the T1D Exchange shows that adolescents with type 1 diabetes have not escaped the global obesity epidemic. Metformin, an oral medication used primarily to treat type 2 diabetes by helping control blood sugar levels and improving insulin resistance, has shown significant potential benefits among adults with type 1 diabetes.

However, studies of adolescents have been small, of short duration, produced inconclusive results or did not focus on overweight and obese adolescents. Thus, the researchers sought to assess the efficacy and safety of metformin as an adjunct therapy in overweight adolescents with type 1 diabetes. They studied changes in HbA1c levels – a fundamental measure of diabetes management – as a primary outcome. They also explored changes in total daily insulin and fluctuations in blinded continuous glucose monitors, BMI/body composition, blood pressure and lipids.

"Being overweight or obese with type 1 diabetes has potentially serious metabolic consequences, especially for adolescents," said author Kristen J. Nadeau, MD, a T1D Exchange investigator and pediatric endocrinologist at Children's Hospital Colorado. "They are at higher risk for insulin resistance and cardiovascular disease, which is the leading cause of death for type 1 patients. While metformin did not improve glycemic control in this study population, its effect on improving cardiovascular risk factors makes it a potential resource for tackling the ongoing obesity epidemic." 

Over six months, 140 participants with type 1 diabetes ages 12 to 19 participated in a clinical trial at 26 sites in the T1D Exchange Clinic Network. Participants were assigned either metformin or a placebo randomly; had follow-up visits at six, 13 and 26 weeks, with additional phone contact at 20 weeks. While the researchers observed an initial improvement in HbA1c at three months, the conclusion of the trial showed no statistical or clinical differences in HbA1c from baseline to 26 weeks between the metformin and the placebo groups.

While the addition of metformin to daily insulin therapy did not improve glycemic outcomes in overweight and obese adolescents with type 1 diabetes, researchers did observe beneficial secondary findings. Importantly, they found metformin led to a reduction in insulin doses, suggesting improved insulin sensitivity and improvement in measures of adiposity.

Further, it was associated with reductions in cardiovascular disease risk factors:

• 17 percent of the metformin group and just seven percent of the placebo group experienced a greater than five percent reduction in body weight from baseline to 26 weeks;
• 24 percent and 41 percent of the metformin and placebo groups, respectively, had a greater than 5 percent increase in weight during the study; and
• 24 percent of the metformin and seven percent of the placebo group reduced BMI by at least 10 percent from baseline to 26 weeks.

"The changes in body weight, body composition and insulin requirements may have improved insulin sensitivity, which we consider a beneficial effect," said co-author Ingrid M. Libman, MD, PhD, associate professor in the Division of Pediatric Endocrinology and Diabetes at Children's Hospital of Pittsburgh of UPMC. "The next step for this research is to fully explore the potential benefits of metformin on cardiovascular risk factors in patients with type 1 diabetes."

More research is also needed to determine metformin's impact on diabetic complications, added Nadeau, as the six-month study period may have been too short to show long-term beneficial effects. Another potential limitation of the study was the possibility that the participants' compliance with metformin decreased over time.

Studies such as these provide valuable insight for the type 1 diabetes community, according to Henry Anhalt, DO, chief medical officer at T1D Exchange. "Our goal is to improve standards of care in treatment and management of this disease and that can only be done with strong collaboration among the patient community, clinicians and scientists. All research is important; the results inform and guide the community while opening new pathways for scientists to explore."

Moreover, noted Libman, while there are many options for treatment of type 2 diabetes in adults, insulin continues to be the only effective medication for type 1, irrespective of age.

"Repurposing available drugs is a very promising therapeutic avenue that JDRF is pursuing," said Sanjoy Dutta, PhD, assistant vice president of Translational Development at JDRF. "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."

About T1D Exchange
T1D Exchange, the first program of Unitio, was founded on the premise that finding faster, better therapies for type 1 diabetes (T1D) requires a research model as multi-faceted as the disease itself. T1D Exchange acts as a convener of the many thousands of people working to improve patient outcomes – by connecting them to one another and to the patient community at large. Drawing on decades of earlier research and data, T1D Exchange aims to be the translational engine that enables the entire T1D ecosystem to collaborate in truly novel ways via the integration of a Clinic Network, Clinic Registry, Biobank, and the online patient/caregiver community, Glu.

About JDRF
JDRF is the leading global organization funding type 1 diabetes (T1D) research. Our mission is to accelerate life-changing breakthroughs to cure, prevent and treat T1D and its complications. To accomplish this, JDRF has invested nearly $2 billion in research funding since our inception. We are an organization built on a grassroots model of people connecting in their local communities, collaborating regionally for efficiency and broader fundraising impact, and uniting on a national stage to pool resources, passion, and energy. We collaborate with academic institutions, policymakers, and corporate and industry partners to develop and deliver a pipeline of innovative therapies to people living with T1D. Our staff and volunteers in more than 100 locations throughout the United States and our six international affiliates are dedicated to advocacy, community engagement and our vision of a world without T1D. For more information, please visit jdrf.org or follow us on Twitter: @JDRF.

Contact: Haley Schwartz, 212-715-1573, [email protected]

SOURCE T1D Exchange; JDRF

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