Evaluating the efficacy and safety of alogliptin in combination with pioglitazone in patients with type 2 diabetes mellitus uncontrolled with metformin

This study tested the efficacy of the drug combination containing alogliptin and pioglitazone in patients with type 2 diabetes mellitus (T2DM) uncontrolled with high doses of metformin. The results showed that the combination of the two drugs was able to better control blood glucose levels than metformin alone.

In T2DM, either the pancreas does not produce enough insulin, or the body does not use the insulin properly (a process called insulin resistance). Insulin is necessary for the body to use glucose for energy. Initial treatment for T2DM typically involves lifestyle changes and metformin. When these methods fail to control glucose levels, doctors will often add insulin or other oral anti-diabetic drugs (OAD). Alogliptin (Nesina) is an OAD approved by the U.S. FDA as therapy for patients with T2DM that works by stimulating the release of insulin after a meal. Pioglitazone (Actos) is another OAD approved by the U.S. FDA for the treatment of T2DM that works by increasing the body’s sensitivity to insulin, thus helping to reduce insulin resistance. Studies suggest that combining various OAD with different mechanisms of action may be the key to best control glucose levels in patients with T2DM.

This study included 1554 T2DM patients who were being treated with metformin. In addition to metformin, the patients were randomly assigned to one in four therapy options: alogliptin alone, pioglitazone alone, alogliptin with pioglitazone and placebo (a substance with no medical effect, used as a control in testing new drugs). The main parameter measured was the value of glycated hemoglobin or HbA1c (a test that shows an average of the blood sugar control of the last 2 to 3 months). After 26 weeks of treatment, patients treated with the combination of alogliptin and pioglitazone in addition to metformin had a significant lower HbA1c compared to patients treated with the drugs alone. The drug combination also caused an improvement in insulin secretion from the pancreas and in the body’s sensitivity to insulin, both indicators of an effective treatment for T2DM. The drug combination did not appear the influence body weight and hypoglycemia (low blood sugar) was uncommon during the treatment period.

In summary, this study showed that the combination of alogliptin and pioglitazone in addition to metformin was well tolerated and was associated with a significant improvement in blood sugar control.

A limitation of this study is its short follow up period. Future studies should assess the effects of this drug combination for longer periods of time.