Combination Therapy with Metformin plus Gliclazide in Patients with Type 2 Diabetes

Type 2 diabetes is a chronic, degenerative disease, which requires management of the symptoms via lifestyle modification and anti-diabetic pharmacotherapies. If glycaemic targets are not maintained, patients can often require the addition of a second drug to help achieve glycaemic control. Polypharmacy represents a substantial problem in some patient groups, reducing adherence and potentially impacting on clinical outcomes. Patients with type 2 diabetes may be taking a number of concomitant medications. For this reason, a single-tablet, combined therapy is an attractive prospect for achieving and maintaining glycaemic targets, reducing complexity and burden on patients, while promoting adherence. Metformin is widely used as a monotherapy, acting to improve insulin sensitivity, reducing glucose production and increasing uptake and utilisation of glucose in tissues. Gliclazide, a second generation sulfonylurea, stimulates the production of insulin. Combination of metformin and gliclazide is an appealing dual therapy option due to their complementary modes of action. The efficacy and safety of a range of combination therapies have been investigated in a number of clinical trials. In patients with inadequate glycaemic control, combination of metformin and gliclazide has consistently demonstrated favourable efficacy in clinical trials, reducing glycated haemoglobin, fasting blood glucose and post-prandial glucose. Both therapies are well-tolerated and show comparable, if not favourable safety profiles, including hypoglycaemia, weight loss, cardiovascular measures, and some evidence of benefits to oxidative status. In this review, we evaluate the efficacy and safety evidence supporting combined metformin and gliclazide therapy for the treatment of type 2 diabetes and consider the wider benefits of combining these drugs as a single tablet.