Counteracting insulin resistance with metformin

There are many type 1 diabetes patients who, despite insulin therapy, have poor metabolic control and high HbA1c values. This is often due to increased insulin resistance, which requires high doses of insulin. Could the additional oral administration of metformin be an option?

Options for patients with type 1 diabetes and poor blood glucose control

Patients with type 1 diabetes who, despite insulin therapy, have poor metabolic control with clearly too high HbA1c values are frequently encountered. This is often due to increased insulin resistance, which requires high doses of insulin. Could the additional administration of the oral antidiabetic metformin be a possible option?

There are many reasons for the rise in insulin resistance in type 1 diabetes. Standard insulin therapy can promote weight gain and dyslipidemia, which are known risk factors for increasing insulin resistance. If this leads to a full evolution into a metabolic syndrome, it is also referred to as "double diabetes". In addition to obesity, lack of exercise also contributes to insulin resistance in type 1 diabetes. Insulin resistance (in this case due to hormones) is also blamed for the poorer diabetes control during puberty.

Insulin resistance promotes weight gain and hypoglycemic risk

The higher insulin doses required for insulin resistance significantly increase body weight and the risk of hypoglycemia, which often leads to non-compliance and thus to a deterioration in blood glucose control.

Metformin, previously mainly used in type 2 diabetes, can counteract insulin resistance through various mechanisms. It increases insulin sensitivity in the liver by inhibiting hepatic glucose production - in skeletal muscle and adipocytes it promotes glucose uptake. Both lead to improved insulin efficacy and thus to better blood sugar control. This effect has long been used in patients with type 2 diabetes in addition to insulin therapy - it has not yet been officially recommended for type 1 diabetes and is only used in individual cases.

12 months metformin in addition to insulin therapy

Selvihan Beysel et al. from the Eiskisehir State Hospital, Turkey, retrospectively evaluated 29 such individual cases with 12-month metformin therapy and compared them with as many patients with type 1 diabetes without additional metformin therapy. Care was taken to ensure that the two groups did not differ significantly in age, sex, weight, required insulin dose, duration of diabetes, blood pressure, obesity, glucose and lipid levels. The rate of metabolic syndrome did not differ before therapy began (44.8 vs. 41.4%). All patients included had an HbA1c value > 7.5% before therapy, were on average 29.01 years old, had a BMI of 24.18 kg/m2 and an average diabetes duration of about 12 years. Most of them were treated with intensified insulin therapy, a few in the metformin group had an insulin pump (3.4%).

Reduction of patients with metabolic syndrome

After 12 months of metformin therapy, the proportion of patients with metabolic syndrome (-9.8% vs. -2.5%) decreased significantly compared to insulin alone. Mean insulin requirements were significantly lower in the metformin group and fasting blood glucose and post-meal blood glucose levels had decreased significantly more. The changes in body weight, waist circumference, and lipid values did not differ between the two groups and the differences in the improvement in HbA1c (-0.8% vs. -0.3%) were not significant either.

Lower insulin requirements under metformin

The authors concluded that the additional administration of metformin to insulin therapy over 12 months can significantly improve blood sugar levels in patients with poorly adjusted type 1 diabetes and reduce insulin requirements - irrespective of the development of body weight and lipid levels. The proportion of patients with metabolic syndrome as an expression of insulin resistance is declining significantly. This effect should now be further investigated in larger controlled trials in patients with type 1 diabetes, poor blood sugar control, and high insulin requirements.

Selvihan Beysel et al; The effects of metformin in type 1 diabetes mellitus; BMC Endocrine Disorders (2018); 18:1; DOI 10.1186/s12902-017-0228-9.

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