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Abstract
AimTo investigate the efficacy and safety of a dipeptidyl peptidase-4 inhibitor, sitagliptin, for treating diabetes mellitus complicated by chronic liver injury.MethodsSitagliptin was administered for 13.7 ± 10.1 months to 122 patients with DM complicated by chronic liver injury (including 19 patients with liver cirrhosis), and changes in hemoglobin A1c (HbA1c) and liver enzymes (transaminases, etc.) were evaluated.ResultsHbA1c was reduced from 8.48 ± 1.43% to 7.87 ± 1.35% (P < 0.001). Among liver enzymes, alanine aminotransferase (ALT) levels improved from 75.1 ± 45.2 to 65.8 ± 35.8 IU/L (P = 0.012) and gamma-glut amyl-trans peptidase from 155.2 ± 161.1 to 133.2 ± 127.4 IU/L (P = 0.044). Among the causes of liver injury, non-alcoholic fatty liver disease and alcoholic liver disease both showed the reductions in HbA1c with no deterioration of liver enzymes. An analysis of 19 patients with liver cirrhosis also showed reductions in HbA1c with no deterioration of liver enzymes.ConclusionIt is suggested that sitagliptin can be administered effectively and safely to patients with diabetes mellitus complicated by chronic liver injury, including liver cirrhosis.
Highlights
The number of patients with diabetes mellitus (DM) is increasing recently in Japan, was estimated at 9.5 million cases in 2012 in reports by Japanese Ministry of Health, Labor and Welfare
Nineteen patients were diagnosed with liver cirrhosis (LC), 10 with Alcoholic liver disease (ALD), 6 with chronic hepatitis C (C–CH), 2 with non-alcoholic fatty liver disease (NAFLD) and one with Autoimmune hepatitis (AIH)
Two patients with NAFLD were considered to develop nonalcoholic steatohepatitis (NASH), which shows the ballooning of hepatocytes, proliferation of inflammatory cells, and hepatic fibrosis in histology
Summary
The number of patients with diabetes mellitus (DM) is increasing recently in Japan, was estimated at 9.5 million cases in 2012 in reports by Japanese Ministry of Health, Labor and Welfare. Dipeptidyl-peptidase 4 (DPP-4) inhibitors have recently been developed as a new viable option for the treatment of DM other than for type 1 DM (T1DM), and the first DPP-4 inhibitor in Japan, sitagliptin, was released in 2009. The incretin hormones glucagon-like peptide-1 (GLP1) and glucose-dependent insulinotropic polypeptide (GIP) are released from the gastrointestinal tract in response to a meal, which stimulates glucose-dependent insulin production and secretion via specific receptors expressed on the islet β cells (Drucker 2002). DPP-4 inhibitors exhibit serum glucose-decreasing action by inhibiting the decomposition of incretin hormones and increasing of insulin secretion (Drucker and Nauck 2006; Ahren 2007; Holst et al 2009; Omar and Ahren 2014). DPP-4 inhibitors inhibit glucagon secretion, increase islet cell proliferation, and decrease cell apoptosis in vitro
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