Volume 6, Issue 2 September 2012
DPP-4 inhibitors are indicated for the improvement of glycaemic control in adults with type 2 diabetes mellitus. Drugs of this class include Onglyza▼ (saxagliptin), Trajenta▼ (linagliptin), Galvus▼ (vildagliptin) and Januvia (sitagliptin). A number of fixed-dose combination tablets containing a DDP-4 inhibitor with metformin are also available, including Eucreas▼ (vildagliptin) and Janumet (sitagliptin).
An increased risk of acute pancreatitis has been identified for all approved DPP-4 inhibitors. For most of the compounds this was detected in spontaneous post-marketing reports; for one of the newer compounds, linagliptin, a small increased number of cases compared with placebo was detected in clinical development.
Consequently, pancreatitis is now included in the product information for all DPP-4 inhibitors as a possible adverse reaction. The reporting rate of pancreatitis appears to be low (ranging between 1/1 000 and 1/100 patients receiving the drug) but the precise frequency is unknown as few cases have been reported in clinical trials. In most cases, pancreatitis resolved after discontinuation of treatment.
The possible mechanism leading to acute pancreatitis is not clear. Data from animal studies have been inconclusive or have not suggested a safety concern. In addition, patients with diabetes are known to have a higher incidence of pancreatitis compared with non-diabetic patients.
Advice for healthcare professionals:
BNF section 6.1.2. Antidiabetic drugs
Article citation: Drug Safety Update September 2012, vol 6, issue 2: A3