The clinical benefits of good glycaemic control are well established . However, the traditional stepwise approach beginning with diet and exercise and sequentially adding and titrating does not address the multifactorial nature of T2DM and the critical value of early intervention to avoid progressive beta-cell failure . The most recent modification of the American Diabetes Association (ADA) recommendations goes beyond the evidence-based target HbA1c of less than 7% for diabetes populations at large and calls for individualized goals for patients to attempt to achieve a HbA1c target as close to normal as possible without significant hypoglycaemia and/or unwanted adverse events (AEs) . This recommendation implies that patients with T2DM will require multiple pharmacological combinations much earlier to accomplish these goals, with careful therapy selection to avoid AEs and hypoglycaemia. Indeed, most recent guidelines for the pharmacological management of T2DM have become more aggressive, with specific recommendations on the progressive use of combination strategies if HbA1c remains more than 7% in an attempt to attain and sustain the increasingly stringent glycaemic targets .
However, clinical inertia with failure to advance therapy despite persistently elevated HbA1c levels above target has been a major problem [5,6], but perhaps the increasing use of combination therapy as a first-line intervention in T2DM may facilitate resolution of this compliance issue.
Initial combination therapy using two Oral Antidiabetic Drug (OAD) with complementary mechanisms of action is an alternative approach that may provide better or more sustained glycaemic control, or allow the use of lower doses of the component OADs to minimize any dose-related AEs.
Vildagliptin is a selective dipeptidyl peptidase (DPP)-4 inhibitor that improves glycaemic control in patients with T2DM by increasing both α- and β-cell responsiveness to glucose [7,8]. Vildagliptin has been shown to decrease HbA1c when given as monotherapy [9,10] or in combination with metformin , but its effects in combination with a thiazolidinedione (TZD) remain to be determined.
The present study compared the efficacy and tolerability of initial combination therapy with vildagliptin, which improves islet function, and the TZD pioglitazone, which enhances insulin sensitivity, to the monotherapy components. For the monotherapy arms, doses of 100 mg q.d. for vildagliptin and 30 mg q.d. for pioglitazone were chosen and compared with the combination of vildagliptin/pioglitazone (100/30 mg q.d.) and to a low-dose combination of 50/15 mg q.d.