Time to change the status quo? A look at initial treatment options for type 2 diabetes

This study examined whether initial treatment with three drugs was more effective than the traditional treatment method of adding medications over time for type 2 diabetes.

Type 2 diabetes is a progressive disease. The cells that produce insulin (beta cells) begin to fail well before the disease is diagnosed, and continue to lose function over time. This increases the need for medications and insulin therapy in order to control blood glucose (sugar) levels. Metformin (Glucophage) is generally the first glucose-lowering medication used by type 2 diabetes patients. When that fails to control blood glucose, sulfonylureas (such as glipizide [Glucotrol]), and then insulin are added. However, neither metformin nor sulfonylureas protect beta cells from failure.

Glucagon-like pepetide-1 (GLP-1) agonists (such as exenatide [Bydureon]) increase insulin production and protect beta cells from failing. Thiazolidinediones (such as pioglitazone [Actos]) increase the body’s sensitivity to insulin, and also protect beta cell function. It is not clear whether use of these therapies as initial treatments, along with metformin, can improve beta cell function and blood glucose control in patients with type 2 diabetes.

This study examined whether a triple therapy (metformin, pioglitazone, and exenatide), was as effective at controlling blood glucose as conventional therapy (metformin, followed by the addition of a sulfonylurea and then insulin) in type 2 diabetes. In this study, 157 patients were randomly assigned to receive triple therapy (71 patients) or conventional therapy (86 patients). Patients were treated for 2 years. Every 3 months, HbA1c (average measure of blood glucose over 3 months), fasting blood glucose (glucose levels after a period without food or drink), and body weight were measured.

HbA1c decreased over the first 6 months of treatment in both groups. At 6 months, patients in the triple therapy group had significantly lower HbA1c levels (6.0%) compared to those receiving conventional therapy (6.2%). By 24 months, average HbA1c levels had increased to 6.5% in the conventional therapy group, and had remained at 5.95% for those in the triple therapy group. More than 90% of the patients in the triple therapy group were able to maintain HbA1c levels lower than 7.0%, compared to less than 75% of those in the conventional therapy group.

Fasting blood glucose levels were significantly lower at 6 months and 24 months in the triple therapy group. Patients in the triple therapy group lost an average of 1.2 kg (2.6 lbs), while patients in the conventional therapy group gained 4.1 kg (9 lbs) over 24 months.

Mild hypoglycemia (low blood glucose levels) was experienced by 46% of the conventional therapy group and 14% of the triple therapy group. Patients in the triple therapy group reported more gastrointestinal side effects, as well as swelling in the arms or legs.

This study concluded that initial treatment with three types of glucose-lowering medications led to larger decreases in HbA1c than did conventional therapies.