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Sitagliptin: results from clinical practice

Accepted: 14 August 2013; published online: 4 September 2013 Citation: Curr Med Res Opin 2013; 29:1483–5 According to the latest American Diabetes Association (ADA) guidelines, lowering glycated hemoglobin (HbA1c) to below or around 7% has been shown to reduce microvascular and neuropathic complications of diabetes and, if implemented soon after the diagnosis of diabetes, is associated with long-term reduction of macrovascular disease. To help in achieving this goal, in recent years the new class of incretins has been developed as an additional option for the treatment of type 2 diabetes mellitus. Incretins are secreted by intestinal L-cells, mainly in response to food intake; the most important incretin, glucagon-like peptide-1 (GLP-1), has everal actions including stimulation of insulin secretion and reduction of glucagon secretion, both in a glucose-dependent manner, resulting in reduced hepatic glucose production, delayed gastric emptying, and increased sense of satiety. GLP-1 is rapidly degraded by dipeptidyl peptidase-4 (DPP-4), that limits GLP-1 time of action in the blood. Actually two classes of drugs based on the incretin system are available: GLP-1 receptor agonists such as exenatide and liraglutide, resistant to DPP-4 cleavage, and DPP-4 inhibitors that delay endogenous degradation of GLP-1. The first DPP-4 inhibitor released for use in clinical practice was sitagliptin, followed by vildagliptin, saxagliptin and linagliptin. Sitagliptin can be used either as monotherapy or in combination. As monotherapy, sitagliptin is indicated in the USA as an adjunct to diet and exercise to improve glycemic control in patients with type 2 diabetes mellitus, whereas in Europe, it is indicated as monotherapy in patients who have inadequate glycemic control with diet and exercise and in whom metformin is inappropriate due to contraindications or intolerance. Sitagliptin is also indicated, both in the USA and in Europe, in combination with metformin, sulfonylureas or pioglitazone in patients who have inadequate control with these agents used as monotherapy in addition to diet and exercise. Sitagliptin is also indicated as triple therapy in combination with metformin plus a sulfonylurea or metformin plus pioglitazone in patients who have inadequate glycemic control with the two agents. Recently, sitagliptin was also approved to be used in combination with insulin. Sitagliptin has been licensed at the recommended dose of 100 mg once daily; in patients with mild renal insufficiency (creatinine clearance [CrCl] 50 ml/min) no dosage adjustment is required. In patients with moderate renal insufficiency (CrCl 30 to550 ml/min), instead, the dose of sitagliptin should be reduced to 50 mg once daily, while in patients with severe renal insufficiency (CrCl530 ml/min) or with end-stage renal disease requiring hemodialysis or peritoneal dialysis, the dose of sitagliptin should be further reduced to 25 mg once daily. In the literature there are several studies about sitagliptin, used both alone and in combination with other anti-diabetic drugs, showing it to be safe and effective. Sitagliptin administered in monotherapy proved to be non-inferior to metformin in improving HbA1c in treatment-naı̈ve patients with type 2 diabetes.