To the Editor: Metformin is a commonly prescribed oral hypoglycaemic agent used to treat type 2 diabetes mellitus. Its major effect is on hepatic glucose production and thereby fasting blood glucose level (f-BGL). Metformin does not commonly cause weight gain, and may be associated with significant weight loss.1

Over the past year, we have prescribed metformin as adjunctive therapy for five patients with type 1 diabetes (T1DM). The patients were selected because of ongoing difficulty controlling f-BGL without hypoglycaemia. T1DM was diagnosed following hyperglycaemia and positive anti-GAD-antibody 56 U/L (normal <9) (patient 1) or ketoacidosis and undetectable C-peptide (patients 2–5). Relevant patient characteristics are shown in the Box. Four patients experienced mild hypoglycaemia as f-BGL was stabilised over 2–4 weeks. No severe hypoglycaemia occurred.

Adjunctive metformin treatment was associated with significantly reduced daily insulin requirements (mean±SD, 0.8±0.1 vs 1.3±0.3 U/kg per day; P = 0.022) and HbA1c (7.4%±1.3% vs 8.4%±1.2%; P = 0.0085).

Controlling f-BGL can be particularly difficult in T1DM. Fasting hyperglycaemia is due to increased hepatic glucose production, related to portal insulin deficiency and counter-regulatory hormones, including growth hormone and cortisol. Therapeutic options to improve f-BGL are limited. Large doses of bedtime intermediate or long-acting insulin increase the risk of hypoglycaemia. Insulin pump-therapy may control glucose levels, but is expensive, associated with weight gain, and is often not preferred by patients.

Obesity is associated with insulin resistance, and intensive insulin treatment is associated with weight gain. Hypoglycaemia can also lead to weight gain if episodes are over-treated. Thus, people with T1DM may become overweight and insulin resistant. Metformin may help to break the spiral of weight gain, hyperglycaemia, increased insulin requirements, and further weight gain.2

Two recent, small studies have examined metformin in T1DM. One study, in patients using insulin pumps, showed decreased daily insulin requirements, but no change in HbA1c.3 These patients were initially receiving a mean dose of 0.72 U/kg per day, suggesting that they were not significantly insulin resistant, unlike our patients. The other study included patients with a high insulin requirement (>1 U/kg per day) and found significant decreases in insulin requirement, f-BGL and HbA1c, consistent with our findings.4

The patients should be carefully selected, as metformin is not routinely indicated for T1DM. The major concern is metabolic acidosis, and metformin is contraindicated where ketoacidosis is an ongoing concern, and in metabolic acidosis or catabolic states. Metformin should be ceased when sick-day management commences.

With these caveats, we believe that metformin can contribute towards improving glycaemic control in patients with T1DM.