Abstract

SIDE EFFECTS OF DPP4 INHIBITORS

Anuj Maheshwari, MD, FACP, FRCP (London, Edinburgh)†*, Ajoy Tewari, MD, FACP, FRCP (London, Edinburgh, Glasgow)†

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Abstract

Dipeptidyl peptidase 4 (DPP4) inhibitors (gliptins) are a recent addition to armamentarium of oral medications to treat type 2 diabetes (T2DM). Initial agent, sitagliptin, was introduced in 2006, followed by others including linagliptin, vildagliptin, saxagliptin, evogliptin and alogliptin. DPP4 enzyme promotes degradation of incretins GLP1 and GIP. Gliptins inhibit breakdown of incretins enhancing insulin secretion and reducing glucagon release, inducing increased glucose uptake and decline in glucose production. Gliptins are approved for treatment of type 2 diabetes and should not be used in patients with type 1 diabetes or diabetic ketoacidosis. Contraindications include hypersensitivity reactions, e.g. anaphylaxis, ‘Stevens-Johnson syndrome’, pancreatitis and severe hypertriglyceridemia. Adverse effects such as nasopharyngitis, headaches, dizziness, arthralgia, nausea, vomiting, diarrhea and constipation are minor and transient. Risk of hypoglycemia is minimal with monotherapy but rises in combination with sulfonylureas and insulin. Cardiovascular outcomes in metaanalyses of trials indicate no increased risk of hospitalization for heart failure. However, caution is advised for patients with moderate to severe heart failure. Renal outcomes are not increased. However, accumulation and excretion of gliptins vary in patients with impaired renal function. Therefore, patients with chronic kidney or end-stage renal disease require dosage adjustments for certain drugs. In conclusion, this review provides mechanism of action, indications, contraindications, potential adverse effects as well as cardiovascular and renal outcomes. Moreover, the review highlights the importance of cost efficacy and safety with a focus on individual patient characteristics.

Keywords: DPP4, Diabetes mellitus, Contraindications, Hypoglycaemia.