Effect of Metformin Added to Insulin on Glycemic Control Among Obese Adolescents with Type 1 Diabetes

Studies currently show that 24% of children and adolescents with Type 1 Diabetes are overweight and 15% are obese. The need for high doses of insulin may further promote weight gain. Additionally, insulin resistance has been associated with increased risk for cardiovascular risk factors. Metformin lowers glucose and was associated with low insulin doses without having an effect on A1C.

A trial was conducted using patients aged 12 to 19 diagnosed with Type 1 Diabetes for at least one year who had an insulin pump or administered at least 3 injections of insulin each day. The patients had an A1C between 7.5% and 9.9% and were in the 85th percentile for BMI. The patients were given 500 mg of metformin that was titrated over 4 weeks to reach 2000mg daily. The rest of the patients were given a placebo.

The baseline A1C was 8.8% in each both groups. At 13 weeks, the mean change in the metformin group was -0.2% and 0.1% in the placebo group. However at 26 weeks, the mean change in the metformin group was 0% and 0.3% in the placebo group. There was no significant difference for glycemic control. However, the patients in the metformin group used less insulin throughout the 26 weeks than the patients on the placebo and more patients in the metformin group maintained or lost weight.

In conclusion, metformin did not improve glycemic control in children or adolescents with Type 1 Diabetes. A few outcomes were favored but not significantly. Additionally, taking metformin increases the risk of GI adverse effects. Therefore, it is not indicated to prescribe metformin to this patient population.

This is interesting because many people do not fully understand the difference between Type 1 and Type 2 Diabetes and the medications to treat each. It is important to know what medications are indicated for each to educate children and parents. Thoughts on another oral medication that may be better suited for this patient population?

JAMA. 2015;314(21):2241-2250. 

Effect of Insulin Glargine Up-titration vs Insulin Degludec/Liraglutide on Glycated Hemoglobin Levels in Patients With Uncontrolled Type 2 Diabetes: The DUAL V Randomized Clinical Trial

In this interesting study the researchers looked to see if degludec /liraglutide was noninferior to continued titration of glargine in patients with uncontrolled type 2 diabetes treated with insulin glargine and metformin. The study occurred at 75 sites in 10 countries with 557 participants with A1Cs of 7% to 10%.  The study measure A1c over a 26 week period with a nonineriority margin of 0.3%. This study is very important because even with insulin therapy, managing blood glucose is a very difficult task in patients with type 2 diabetes.

The study ended up showing the two medications did not show a reasonable difference in achieve A1c after 26 week. However, both medications showed reduction in A1c over the 26 weeks. The researchers did call for more long term studies to determine long term efficacy and safety. These findings could be very important in the future treatment of type 2 diabetes and as the authors said it is very difficult to achieve glycemic control in patients with type 2 diabetes.

With so many people getting diagnosed with type 2 diabetes and it being so difficult to control I wonder how much of it has to do with the patient and how much of it has to do with the medical providers and medication. Diet and personal health plays a role in type 2 diabetes so that much is on the patient. Also I have the feeling that patients with type 2 diabetes don’t see the severity of the disease in comparison to patients with type 1 which leads to adherence problems. On the other hand is the drug therapy not effective enough or the medication being prescribed for individual patients not effective enough?  Either way I hope medical providers will find a way to effectively control type 2 diabetes in the majority of patients.

Lingvay I, Manghi FP, Garcia-Hernandez P, et al. Effect of Insulin Glargine Up-titration vs Insulin Degludec/Liraglutide on Glycated Hemoglobin Levels in Patients With Uncontrolled Type 2 Diabetes: The DUAL V Randomized Clinical Trial. JAMA. 2016;315(9):898-907.

JAMA. 2016;315(9):898-907.

Metformin vs. Insulin Treatment in Gestational Diabetes: Developmental Outcomes

Gestational diabetes has been primarily treated with insulin, which does not cross the placental barrier. However, the use of metformin, which does cross the placental barrier, to treat gestational diabetes is becoming increasingly more common. The researchers in this study aim to examine the offspring of these women treated with either insulin or metformin during their pregnancy, and compare the safety of these two treatment methods.

The study design was a prospective follow-up study, involving children whose mothers had been treated for gestational diabetes with either metformin for gestational diabetes. In the original trial, 751 women from either Australia or New Zealand were participants who were randomly assigned to either insulin or metformin to treat their gestational diabetes. 373 of these women were assigned to take metformin, while 378 were assignment to take insulin. The mothers in this study had consented to be contacted for follow-up after their child’s second birthday. The final number of children included in this follow-up study was 211. The children in the study were evaluated using the Bayley Scales of Infant Development (BSID-II), which consists of three different elements: the Mental Developmental Index (MDI), the Psychomotor Developmental Index and the Behaviour Rating Scale (BRS).

The results of this study concluded that there was no significant difference between the developmental outcomes of children whose mothers had been treated with insulin vs. those whose mothers had been treated with metformin for gestational diabetes. The researchers in the study acknowledge that long-term developmental outcomes have not been studied, and should be in order to get a better idea of the long-term safety of these medications for gestational diabetes.

This study is important because it offers a possible different treatment option for women with gestational diabetes. People typically don’t enjoy giving themselves injections, so with metformin as an option, they won’t have to deal with the needles associated with insulin.

Wouldes TA, Battin M, Coat S, Rush EC, et al. Neurodevelopmental outcome at 2 years in offspring of women randomised to metformin or insulin treatment for gestational diabetes. Arch Dis Child Fetal Neonatal Ed. doi:10.1136/archdischild-2015-309602. (Published 24 February 2016).