Drug Breakdown: Sitagliptin

Day 1: In the 1990s, growing insight into incretin roles in type 2 (T2DM) diabetes led to an interest in the breakdown of gut hormone GLP-1. DPP-4 was identified as the best peptidase target and a piperazine derivative #sitagliptin was found to be a potent and selective inhibitor; licensed in 2006–2007.

Day 2: An oral hypoglycaemic, #sitagliptin was the first DPP-4 inhibitor in class (there are now 5 ‘gliptins’). Not first line, but can be used in adults as monotherapy (with diet/exercise), or as an add-on at various levels of T2DM treatment (including with insulin). With a dose of 100 mg and administered once daily, it also comes as a tablet combination with metformin. It should be noted that a lower dose may be needed if used with other hypoglycaemic agents, such as insulin.

Day 3: Rapid oral absorption (food has no effect) with high bioavailability and Vd. Low plasma protein binding. Minor hepatic CYP3A4 metabolism, but majority renally excreted unchanged (minor in faeces). Dose adjustment if eGFR <45 mL/min, but no dose change for hepatic function, or elderly.