Addition of insulin glargine to combination therapy with oral anti-diabetic drugs: a promising therapeutic option for type 2 diabetes

This study compared the effects of adding insulin glargine treatment  to metformin (Glucophage), glimepiride (Amaryl) or their combination in patients with uncontrolled type 2 diabetes mellitus.

Hyperglycemia (high blood glucose) in type 2 diabetes mellitus arises from a combination of insufficient insulin production and insulin resistance (failure of the cells to respond to insulin). Patients with type 2 diabetes mellitus are often treated using oral anti-diabetic drugs. However, the use of these drugs does not always achieve effective glycemic (blood glucose) control. Glimepiride and metformin are examples of oral anti-diabetic drugs used to treat type 2 diabetes mellitus. Glimepiride increases insulin release from the pancreas while metformin increases the body's response to insulin.

Insulin glargine (Lantus) is a manufactured type of insulin that replaces the insulin that is normally produced by the body. This study aimed to examine the administration of oral anti-diabetic drugs with insulin glargine in patients failing almost maximum doses of oral anti-diabetic drugs.

This study included 99 patients with uncontrolled type 2 diabetes mellitus (blood sugar levels above recommended target ranges) who had failed to achieve glycemic control while taking almost maximal doses of oral anti-diabetic drugs for 4 weeks. After 4 weeks, 33 patients were randomly assigned to receive insulin glargine plus metformin, 34 to receive insulin glargine plus glimepiride while 32 patients received insulin glargine plus glimepiride plus metformin. Glycated hemoglobin or HbA1c (a test that measures an average blood glucose concentration over 2 to 3 months) and fasting blood glucose levels (glucose levels before meals) were used to indicate the efficacy of the treatments.

After 24 weeks of treatment, the glycated hemoglobin levels significantly improved with insulin glargine / glimepiride / metformin compared with insulin glargine / metformin and insulin glargine / glimepiride. The glycated hemoglobin levels were reduced from an average of 8.5% to 7.7% with insulin glargine / metformin, from 8.4% to 7.7% with insulin glargine / glimepiride and from 8.7% to 7.3% with insulin glargine / glimepiride / metformin.

75% of patients treated with insulin glargine / glimepiride / metformin reached a glycated hemoglobin level of 7.5% or less compared to 43.8% in the insulin glargine / metformin group and 56.3% in the insulin glargine / glimepiride group.

Fasting blood glucose levels reduced from 9.0 to 6.9mmol/l with insulin glargine / metformin, from 8.9 to 7.6mmol/l with insulin glargine / glimepiride, and from 9.2 to 6.8mmol/l with insulin glargine / glimepiride / metformin.

The risk of adverse events (harmful and undesired effects resulting from the medication) and hypoglycemia (abnormally low blood glucose levels) was similar among all treatment groups.

In summary, this study concluded that the combination therapy of metformin and glimepiride plus insulin glargine in patients failing therapy with almost maximal doses of oral anti-diabetic drugs resulted in significant improvement in blood glucose control compared with the combination therapy of metformin plus insulin glargine or glimepiride plus insulin glargine.

This study had short treatment duration, as well as a small number of participants in each group. Larger studies are needed in order to confirm the findings of this study.