Dipeptidyl peptidase 4 inhibition with sitagliptin: a new therapy for Type 2 diabetes

Abstract

Sitagliptin is a once-daily, orally active, competitive and fully reversible inhibitor of dipeptidyl peptidase 4, the enzyme that is responsible for the rapid degradation of the incretin hormone glucagon-like peptide-1. It is the first in this new class of antihyperglycaemic agents to gain regulatory approval for the treatment of Type 2 diabetes, both as a monotherapy and for use in combination with metformin or a thiazolidinedione. In clinical trials of ≤ 1-year duration, sitagliptin improves glycaemic control by reducing both fasting and postprandial glucose concentrations, leading to clinically meaningful reductions in glycosylated haemoglobin levels. It is safe and well tolerated, with a side-effect profile that is similar to that of the placebo, a low incidence of hypoglycaemia and body weight neutrality. Further clinical experience with sitagliptin will reveal its long-term durability, safety and efficacy.

Keywords::

• dipeptidyl peptidase 4
• GLP-1
• glucagon-like peptide-1
• glycaemic control
• incretin enhancer
• sitagliptin
• Type 2 diabetes

Disclosure

CF Deacon has received lecture fees from Merck and Prosidion in the last 2 years, as well as being on the Advisory Board for Bristol-Myers Squibb and Takeda Pharmaceuticals.