Effect of Adjunct Metformin Treatment in Patients with Type-1 Diabetes and Persistent Inadequate Glycaemic Control. A Randomized Study
Original source: PLoS ONE 3(10): e3363
Authors: Søren Søgaard Lund (corresponding author), Lise Tarnow, Anne Sofie Astrup, Peter Hovind, Peter Karl Jacobsen, Amra Ciric Alibegovic, Ida Parving, Lotte Pietraszek, Merete Frandsen, Peter Rossing, Hans-Henrik Parving, Allan Arthur Vaag
Publication date: October 9, 2008
DOI (digital document ID): 10.1371/journal.pone.0003363
Requires subscription? No
Publicly-available abstract: Yes
Synopsis:
Despite intensive insulin use, many people who have had Type 1 (autoimmune) diabetes for a long period of time have trouble maintaining adequate glucose control and achieving an HbA1c of under 7%, which is considered a threshold beneath which the risk of developing complications of diabetes is reduced. There are a number of reasons -- physiological (medical), environmental, and psychological -- for poor control. One of the physiological reasons may be the development of insulin resistance over time. This study looks at the potential for adding the use of metformin -- an initial drug of choice in treating Type 2 (metabolic) diabetes (which often includes insulin resistance) -- to the use of insulin to improve blood glucose control in Type 1 diabetes.
The study included 100 Type 1 diabetes patients with poorly-controlled blood glucose levels (defined as HbA1c over 8%). A one-month period in which all of them received identical placebo pills was followed by a three-week period in which the pills of half of the patients was gradually changed to include 1000 mg metformin, twice daily. The other patients continued to receive placebo pills. The patients were followed at one- to three-month intervals, for a period of a year after maximum/target dose was achieved.
The study was conducted as a double-blind study, which means that neither the investigators nor the patients knew who was taking metformin and who was not.
At each clinic visit before and during the study, patients were tested for HbA1c, c-peptide levels (a protein used as an indicator of remaining beta-cell function), and blood glucose level. Their body mass index (BMI -- a comparison of weight to height) was also measured. They were asked to estimate the average of the blood glucose measurements they took themselves at home. They were also requested to report serious adverse effects (including life-threatening events requiring hospitalization, or which resulted in persistent or significant loss of physical abilities, or which caused an adverse reaction due to a birth defect, and hypoglycemic events which resulted in unconsciousness or which required the intervention of a third party) and minor adverse effects (including hypoglycemia mild enough for the patient to be able to treat himself). They were also asked to report any changes to their insulin prescriptions and treatments (change of type of insulin, number of injections per day, sites used, and dosage).
In addition to analyzing the HbA1c measurements of the entire groups (metformin and placebo), researchers counter-checked changes in HbA1c with changes in patient weight and insulin dosage. They also analyzed the measurements from overweight and obese patients separately from those of normal weight, and the results from those taking higher amounts of insulin daily from those taking smaller amounts, since insulin resistance is often treated with higher doses of insulin; it is also associated with overweight and obesity.
The results of the analysis showed no significant changes in HbA1c level for either group. However, the metformin users lost, on average, a little more than a kilogram of body weight and were able to reduce their daily insulin usage by, on average, 0.03 units per kilogram of body weight. By comparison, those patients on placebo did not lose weight and, on average, needed to increase their insulin usage by 0.03 units per kilogram of body weight. (This corresponds to average total daily insulin use of 3 units less per day for the metformin group, and about 2.5 units more per day for the placebo group.)
The results of this study were compared to the results of previous studies, and the strengths and limitations of both this study and those were examined.
Reliability:
The authors are professionals in the fields of endocrinology and diabetes care, associated with accredited institutions. The results were published in a peer-reviewed journal.
The study size was small, so there is some potential for skew.
The use of double-blinding and placebos removed the variables of being able to attribute all good effects to the use of the drug, as well as that of all positive effects being due to the suggestion of the pills being effective.
The duration of the study was long enough to determine whether metformin would have any effect on HbA1c; however, the reduction in insulin use among the metformin patients may have counteracted the drug's effects on lowering HbA1c. The authors note that had they specified that the patients not drop their insulin dosages, there may have been a greater risk of serious hypoglycemic events.
Practical Applications:
The authors suggest that the mild weight reduction and apparent improved insulin sensitivity among the patients treated with metformin may lower these patients' diabetes-related cardiovascular risks; however, metformin does not appear to be a useful tool for improving glycemic control in patients with long-duration Type 1 diabetes.
This synopsis was based on the entire article.
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