medwireNews: Addition of metformin to insulin treatment does not improve glucose control in obese adolescents with Type 1 diabetes, show findings from a randomised trial.
The researchers hoped that metformin, commonly used in Type 2 diabetes, would help to overcome the increased insulin resistance caused by obesity and adolescence in patients with Type 1 diabetes. They recruited 140 patients, aged between 12.1 and 19.6 years, who had a body mass index (BMI) at or above the 85th percentile for age and gender.
There was the appearance of benefit after 13 weeks of treatment. From a starting haemoglobin (HbA1c) level of 8.8%, the 71 patients randomly assigned to take metformin 2000 mg/day in addition to insulin had a 0.2% reduction, compared with a 0.1% increase in the 69 patients assigned to take insulin alone, which was a significant difference.
But after 26 weeks, both groups had a 0.2% increase in HbA1c from baseline, report Kellee Miller (Jaeb Center for Health Research, Tampa, Florida, USA) and co-workers.
“It does not seem likely that different glycemic control results would have been achieved with a longer treatment period”, they write in JAMA.
The team did find some evidence of benefit with metformin, in terms of adiposity and insulin dose. For instance, the weight of patients taking metformin remained stable throughout treatment, whereas that of the placebo group increased by an average of 2 kg, and 24% versus 7% had a BMI reduction of at least 10%.
Also, by week 26, the average daily insulin dose in the metformin group was 0.1 U/kg lower than at baseline, whereas it did not change in the placebo group. In the metformin group, 23% of patients had at least a 25% reduction in average daily insulin dose, whereas just 1% of the placebo group achieved this endpoint.
All these differences were statistically significant; however, the researchers say that the “clinical relevance of these treatment group differences is uncertain.”
Metformin was associated with more adverse events, specifically gastrointestinal events, which occurred in 70% of the metformin-treated patients versus 35% of the placebo group. In addition, there were five episodes of severe hypoglycaemia in the metformin group but none among the placebo-treated patients.
Miller et al say that four of these five events occurred during the first 6 weeks of treatment, during which metformin was increased from 500 mg to 2000 mg per day, and the insulin dose was adjusted accordingly.
“This is noteworthy and suggests careful monitoring during the first few weeks following initiation of any noninsulin drug prescribed for glycemic control”, they write.
By Eleanor McDermid, Senior medwireNews Reporter
JAMA 2015; 314: 2241–2250
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