Tags

Type your tag names separated by a space and hit enter

Sitagliptin in patients with non-alcoholic steatohepatitis: A randomized, placebo-controlled trial.
World J Gastroenterol 2017; 23(1):141-150WJ

Abstract

AIM

To evaluate the effect of sitagliptin vs placebo on histologic and non-histologic parameters of non-alcoholic steatohepatitis (NASH).

METHODS

Twelve patients with biopsy-proven NASH were randomized to sitagliptin (100 mg daily) (n = 6) or placebo (n = 6) for 24 wk. The primary outcome was improvement in liver fibrosis after 24 wk. Secondary outcomes included evaluation of changes in NAFLD activity score (NAS), individual components of NAS (hepatocyte ballooning, lobular inflammation, and steatosis), glycemic control and insulin resistance [including measurements of glycated hemoglobin (HbA1C) and adipocytokines], lipid profile including free fatty acids, adipose distribution measured using magnetic resonance imaging (MRI), and thrombosis markers (platelet aggregation and plasminogen activator inhibitor 1 levels). We also sought to determine the correlation between changes in hepatic fat fraction (%) [as measured using the Iterative Decomposition of water and fat with Echo Asymmetry and Least-squares estimation (IDEAL) MRI technique] and changes in hepatic steatosis on liver biopsy.

RESULTS

Sitagliptin was not significantly better than placebo at reducing liver fibrosis score as measured on liver biopsy (mean difference between sitagliptin and placebo arms, 0.40, P = 0.82). There were no significant improvements evident with the use of sitagliptin vs placebo for the secondary histologic outcomes of NAS total score as well as for the individual components of NAS. Compared to baseline, those patients who received sitagliptin demonstrated improved HbA1C (6.7% ± 0.4% vs 7.9% ± 1.0%, P = 0.02), and trended towards improved adiponectin levels (4.7 ± 3.5 μg/mL vs 3.9 ± 2.7 μg/mL, P = 0.06) and triglyceride levels (1.26 ± 0.43 mmol/L vs 2.80 ± 1.64 mmol/L, P = 0.08). However, when compared with placebo, sitagliptin did not cause a statistically significant improvement in HbA1C (mean difference, -0.7%, P = 0.19) nor triglyceride levels (mean difference -1.10 mmol/L, P = 0.19) but did trend towards improved adiponectin levels only (mean difference, 0.60 μg/mL, P = 0.095). No significant changes in anthropometrics, liver enzymes, other adipocytokines, lipid profile, thrombosis parameters, or adipose distribution were demonstrated. The MRI IDEAL procedure correlated well with steatosis scores obtained on liver biopsy in both groups at baseline and post-treatment, and the Spearman correlation coefficients ranged from r = 0.819 (baseline) to r = 0.878 (post-treatment), P = 0.002.

CONCLUSION

Sitagliptin does not improve fibrosis score or NAS after 24 wk of therapy. The MRI IDEAL technique may be useful for non-invasive measurement of hepatic steatosis.

Authors+Show Affiliations

Tisha R Joy, Department of Medicine, Division of Endocrinology, St. Joseph's Hospital, Western University, London, Ontario N6A 4V2, Canada.Tisha R Joy, Department of Medicine, Division of Endocrinology, St. Joseph's Hospital, Western University, London, Ontario N6A 4V2, Canada.Tisha R Joy, Department of Medicine, Division of Endocrinology, St. Joseph's Hospital, Western University, London, Ontario N6A 4V2, Canada.Tisha R Joy, Department of Medicine, Division of Endocrinology, St. Joseph's Hospital, Western University, London, Ontario N6A 4V2, Canada.Tisha R Joy, Department of Medicine, Division of Endocrinology, St. Joseph's Hospital, Western University, London, Ontario N6A 4V2, Canada.Tisha R Joy, Department of Medicine, Division of Endocrinology, St. Joseph's Hospital, Western University, London, Ontario N6A 4V2, Canada.Tisha R Joy, Department of Medicine, Division of Endocrinology, St. Joseph's Hospital, Western University, London, Ontario N6A 4V2, Canada.Tisha R Joy, Department of Medicine, Division of Endocrinology, St. Joseph's Hospital, Western University, London, Ontario N6A 4V2, Canada.

Pub Type(s)

Journal Article
Randomized Controlled Trial
Validation Study

Language

eng

PubMed ID

28104990

Citation

Joy, Tisha R., et al. "Sitagliptin in Patients With Non-alcoholic Steatohepatitis: a Randomized, Placebo-controlled Trial." World Journal of Gastroenterology, vol. 23, no. 1, 2017, pp. 141-150.
Joy TR, McKenzie CA, Tirona RG, et al. Sitagliptin in patients with non-alcoholic steatohepatitis: A randomized, placebo-controlled trial. World J Gastroenterol. 2017;23(1):141-150.
Joy, T. R., McKenzie, C. A., Tirona, R. G., Summers, K., Seney, S., Chakrabarti, S., ... Beaton, M. D. (2017). Sitagliptin in patients with non-alcoholic steatohepatitis: A randomized, placebo-controlled trial. World Journal of Gastroenterology, 23(1), pp. 141-150. doi:10.3748/wjg.v23.i1.141.
Joy TR, et al. Sitagliptin in Patients With Non-alcoholic Steatohepatitis: a Randomized, Placebo-controlled Trial. World J Gastroenterol. 2017 Jan 7;23(1):141-150. PubMed PMID: 28104990.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Sitagliptin in patients with non-alcoholic steatohepatitis: A randomized, placebo-controlled trial. AU - Joy,Tisha R, AU - McKenzie,Charles A, AU - Tirona,Rommel G, AU - Summers,Kelly, AU - Seney,Shannon, AU - Chakrabarti,Subrata, AU - Malhotra,Neel, AU - Beaton,Melanie D, PY - 2016/09/29/received PY - 2016/12/09/revised PY - 2016/12/21/accepted PY - 2017/1/21/entrez PY - 2017/1/21/pubmed PY - 2017/7/18/medline KW - Fibrosis KW - Hepatic steatosis KW - Insulin resistance KW - Magnetic resonance imaging KW - Non-alcoholic fatty liver disease KW - Non-alcoholic steatohepatitis KW - Platelet aggregation KW - Randomized controlled trial KW - Sitagliptin SP - 141 EP - 150 JF - World journal of gastroenterology JO - World J. Gastroenterol. VL - 23 IS - 1 N2 - AIM: To evaluate the effect of sitagliptin vs placebo on histologic and non-histologic parameters of non-alcoholic steatohepatitis (NASH). METHODS: Twelve patients with biopsy-proven NASH were randomized to sitagliptin (100 mg daily) (n = 6) or placebo (n = 6) for 24 wk. The primary outcome was improvement in liver fibrosis after 24 wk. Secondary outcomes included evaluation of changes in NAFLD activity score (NAS), individual components of NAS (hepatocyte ballooning, lobular inflammation, and steatosis), glycemic control and insulin resistance [including measurements of glycated hemoglobin (HbA1C) and adipocytokines], lipid profile including free fatty acids, adipose distribution measured using magnetic resonance imaging (MRI), and thrombosis markers (platelet aggregation and plasminogen activator inhibitor 1 levels). We also sought to determine the correlation between changes in hepatic fat fraction (%) [as measured using the Iterative Decomposition of water and fat with Echo Asymmetry and Least-squares estimation (IDEAL) MRI technique] and changes in hepatic steatosis on liver biopsy. RESULTS: Sitagliptin was not significantly better than placebo at reducing liver fibrosis score as measured on liver biopsy (mean difference between sitagliptin and placebo arms, 0.40, P = 0.82). There were no significant improvements evident with the use of sitagliptin vs placebo for the secondary histologic outcomes of NAS total score as well as for the individual components of NAS. Compared to baseline, those patients who received sitagliptin demonstrated improved HbA1C (6.7% ± 0.4% vs 7.9% ± 1.0%, P = 0.02), and trended towards improved adiponectin levels (4.7 ± 3.5 μg/mL vs 3.9 ± 2.7 μg/mL, P = 0.06) and triglyceride levels (1.26 ± 0.43 mmol/L vs 2.80 ± 1.64 mmol/L, P = 0.08). However, when compared with placebo, sitagliptin did not cause a statistically significant improvement in HbA1C (mean difference, -0.7%, P = 0.19) nor triglyceride levels (mean difference -1.10 mmol/L, P = 0.19) but did trend towards improved adiponectin levels only (mean difference, 0.60 μg/mL, P = 0.095). No significant changes in anthropometrics, liver enzymes, other adipocytokines, lipid profile, thrombosis parameters, or adipose distribution were demonstrated. The MRI IDEAL procedure correlated well with steatosis scores obtained on liver biopsy in both groups at baseline and post-treatment, and the Spearman correlation coefficients ranged from r = 0.819 (baseline) to r = 0.878 (post-treatment), P = 0.002. CONCLUSION: Sitagliptin does not improve fibrosis score or NAS after 24 wk of therapy. The MRI IDEAL technique may be useful for non-invasive measurement of hepatic steatosis. SN - 2219-2840 UR - https://www.unboundmedicine.com/medline/citation/28104990/Sitagliptin_in_patients_with_non_alcoholic_steatohepatitis:_A_randomized_placebo_controlled_trial_ L2 - http://www.wjgnet.com/1007-9327/full/v23/i1/141.htm DB - PRIME DP - Unbound Medicine ER -