Sitagliptin (
Januvia(®), Xelevia™, Glactiv(®), Tesavel(®)) is an orally administered, potent and highly selective inhibitor of dipeptidyl peptidase-4 (DPP-4) and was the first agent of its class to be approved for use in the management of adults with
type 2 diabetes. Numerous randomized placebo- or active comparator-controlled trials have demonstrated the efficacy of
sitagliptin in terms of improving glycaemic control in patients with
type 2 diabetes, including its use as monotherapy, initial combination
therapy (usually with fixed-dose combinations of
sitagliptin/
metformin), or add-on
therapy to
metformin or to other antihyperglycaemic drugs, with or without
metformin. The primary endpoint of the clinical trials was the reduction from baseline in glycosylated haemoglobin (HbA1c), although
sitagliptin also showed beneficial effects for other endpoints, such as the proportion of patients who achieved target HbA1c, and reductions from baseline in fasting plasma
glucose (FPG) levels and 2-h postprandial
glucose (PPG) levels.
Sitagliptin was generally well tolerated in clinical trials, had a low risk of hypoglycaemia (although this depends on background
therapy) and had a neutral effect on
body weight. Despite concerns regarding a possible increased risk of rare pancreatic adverse events (e.g.
pancreatitis) with
glucagon-like peptide-1 (GLP-1)-based
therapies, such as
GLP-1 receptor agonists and
DPP-4 inhibitors, no causal association has been found; regulators in Europe recently conducted a review of available data, concluding that there is little evidence that these drugs could cause pancreatic
inflammation or
pancreatic cancer. A similar review is planned in the USA and postmarketing surveillance will continue. Thus, oral
sitagliptin is an effective and generally well tolerated treatment option for the management of patients with
type 2 diabetes.