End-stage renal disease (ESRD). Similarly. Liraglutide is not recommended in patients with moderate-to-severe renal function impairment, including ESRD patients. The DPP-4 inhibitors enhance glucose-dependent insulin secretion by preventing DPP-4-mediated degradation of endogenously released incretin hormones. These agents are rapidly becoming a common choice for combination therapy with metformin. Sitagliptin was approved in 2006, followed by vildagliptin (available in the EU and other countries since 2007, still pending for approval in the US), saxagliptin in 2009, alogliptin in 2010 in Japan, and linagliptin in 2011 in the US and a year later in the EU. Despite their common mechanism of action, these agents have structural heterogeneity that translates into different pharmacological properties. DPP-4 inhibitors differ in terms of half-life, systemic exposure, bioavailability, protein binding, metabolism, presence of active metabolism, and excretion routes. These differences may become of interest when considered for patients with renal failure. While sitagliptin, vildagliptin, and saxagliptin have prominent renal elimination, linagliptin is mainly eliminated through the enterohepatic system. AII DPP-4 inhibitors can be used in mild (stages 1 and 2 ) CKD, with no need for dose adjustment. However, for eGFR <50 mL/min/1.73m, a dose reduction is required for all DPP-4 inhibitors, with the exception of linagliptin (Table 3). Accumulation in plasma of DPP-4 inhibitors is considered a potential risk not because of hypoglycemia but, possibly, because of unknown adverse events (AEs). The dose of sitagliptin must be halved (to 50 mg/day) in patients with moderate
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