Case Presentation: A 76-year-old male with a medical history of hypertension, paroxysmal atrial fibrillation, type 2 diabetes mellitus (DM), CKD Stage 3, paraproteinemia/monoclonal gammopathy of unknown significance (MGUS), and obesity presented with dyspnea and generalized weakness. He was admitted for progressive renal failure, uremia, and anasarca. For the duration of his admission his renal function had worsened from his baseline creatinine of 2.2 mg/dL to 4.12 mg/dL, and he developed recurrent episodes of hypoglycemia as low as 48 mg/dL despite the discontinuation of his home medications (insulin glargine, glimepiride, and sitagliptin). His HbA1C was 7%. He was given several ampules of D50 instead of a D10 infusion in order to avoid volume overload. On day 2, his hypoglycemia did not improve, so a D10 infusion (20 ml/hr) was initiated. On day 3, hemodialysis was started for renal failure/anasarca. Despite this, he continued to have hypoglycemic episodes. On day 5, the day of his third dialysis session, his glucose level began to normalize. Over a 5-day period, the patient required a total of 29 ampules of D50 and 72 hours of a D10 infusion. At discharge, his renal function returned to baseline and he was subsequently discharged on insulin glargine and lispro.

Discussion: According to the literature, 87% of sitagliptin (79% unchanged) is excreted through urine. In patients with CKD, both plasma concentrations of sitagliptin and its terminal half-life are increased by four-fold, thus potentiating the risk for hypoglycemia. Current literature also suggests that sitagliptin is well tolerated as monotherapy for patients with type 2 DM and CKD. However, when used in combination therapy in the setting of CKD, as it was used in our patient, there is an increased risk for refractory hypoglycemia. The literature shows that DPP-IV inhibitors are not dialyzable, so emergent hemodialysis is limited as a treatment option. Based upon this data, we believe that our patient’s acute renal failure, superimposed on CKD and paraproteinemia, led to an unexpected increase in the concentration of sitagliptin in plasma. This increased level, in addition to impaired renal clearance, inadvertently resulted in refractory hypoglycemia. Moreover, we believe dialysis aided in the clearance of protein deposition in the kidneys which subsequently improved renal function, therefore allowing sitagliptin to be cleared and hypoglycemia to be correctable using standard measures.

Conclusions: Among U.S. adults aged above 18 years of age with diabetes, 37.0% had CKD (stages 1–4), of which over half had moderate to severe CKD (stage 3 or 4). With such a large prevalence, internists should be aware of the potential for refractory hypoglycemia when sitagliptin is used in combination with other diabetic medications in the setting of CKD as it likely threatens patient safety in the hospital environment.

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