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Liraglutide, Sitagliptin, and Insulin Glargine Added to Metformin in Patients With Type 2 Diabetes Mellitus and Nonalcoholic Fatty Liver Disease
abstract
This abstract is available on the publisher's site.
Access this abstract nowTo investigate the effect of antidiabetic agents on nonalcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes mellitus (T2DM), 75 patients with T2DM and NAFLD under inadequate glycemic control by metformin were randomized (1:1:1) to receive add-on liraglutide, sitagliptin, or insulin glargine in this 26-week trial. The primary endpoint was the change in intrahepatic lipid (IHL) from baseline to week 26 as quantified by magnetic resonance imaging-estimated proton density fat fraction (MRI-PDFF). Secondary endpoints included changes in abdominal adiposity (subcutaneous adipose tissue [SAT] and visceral adipose tissue [VAT]), glycated hemoglobin, and body weight from baseline to week 26. We analysed data from intent-to-treat population. MRI-PDFF, VAT, and weight decreased significantly with liraglutide (15.4% ± 5.6% to 12.5% ± 6.4%, P < 0.001; 171.4 ± 27.8 to 150.5 ± 30.8, P = 0.003; 86.6 ± 12.9 kg to 82.9 ± 11.1 kg, P = 0.005, respectively) and sitagliptin (15.5% ± 5.6% to 11.7% ± 5.0%, P = 0.001; 153.4 ± 31.5 to 139.8 ± 27.3, P = 0.027; 88.2 ± 13.6 kg to 86.5 ± 13.2 kg, P = 0.005, respectively). No significant change in MRI-PDFF, VAT, or body weight was observed with insulin glargine. SAT decreased significantly in the liraglutide group (239.9 ± 69.0 to 211.3 ± 76.1; P = 0.020) but not in the sitagliptin and insulin glargine groups. Changes from baseline in MRI-PDFF, VAT, and body weight were significantly greater with liraglutide than insulin glargine but did not differ significantly between liraglutide and sitagliptin. Conclusion: Combined with metformin, both liraglutide and sitagliptin, but not insulin glargine, reduced body weight, IHL, and VAT in addition to improving glycemic control in patients with T2DM and NAFLD.
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Liraglutide, Sitagliptin, and Insulin Glargine Added to Metformin: The Effect on Body Weight and Intrahepatic Lipid in Patients With Type 2 Diabetes Mellitus and Nonalcoholic Fatty Liver Disease
Hepatology 2019 Jun 01;69(6)2414-2426, J Yan, B Yao, H Kuang, X Yang, Q Huang, T Hong, Y Li, J Dou, W Yang, G Qin, H Yuan, X Xiao, S Luo, Z Shan, H Deng, Y Tan, F Xu, W Xu, L Zeng, Z Kang, J WengFrom MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
Great advances are taking place currently to manage metabolic syndrome and especially the diabetic portion of MS. We currently have excellent control over lipid abnormalities and have yet to formalize first-line treatment directly for NASH except for vitamin E (and possibly pioglitazone), recognizing there are over 60 medications or tools in preclinical or clinical development. Large shifts have taken place in the last 5 years in the management of type 2 diabetes mellitus with the relegation of insulin to a 3- or 4-level use due to the fact it is associated with weight gain and given recent insights in cancer promotion. Current data support the sequential or add-on use of GLP agonists, DPP inhibitors, and SGLT transport inhibitors that are, importantly, associated with weight loss, decreased appetite, and improvement in NASH in biopsy studies; and, where biopsy information is not available, ALT improvement or changes in imaging such as ultrasound, MR PDFF, and VCTE/CAP scores. As hepatologists, and now metabologists, we need to partner with our diabetologist colleagues to restructure diabetes mellitus management to aid in MS treatment, with optimistic changes in weight and behavior and ultimately decreasing rates of cirrhosis, liver failure, liver transplant, and liver cancer.
Non-alcoholic fatty liver disease (NAFLD) is highly prevalent in patients with type 2 diabetes (T2D) and can progress to non-alcoholic steatohepatitis and cirrhosis. In addition, NAFLD is a marker of very high cardiovascular risk in T2D. There have been few studies comparing more than two glucose-lowering medications on NAFLD in patients with T2D.
Yan et al randomly compared the effect of 26 weeks of liraglutide 1.8 mg, sitagliptin 100 mg, or glargine titrated to fasting plasma glucose <7 mmol/L, added to metformin, on 26-week hepatic and metabolic outcomes in 75 patients with T2D and NAFLD confirmed by MRI protein density fat fraction (MRI-PDFF) >10%. GRADE, a long-term comparative-effectiveness study including these three medications and glimepiride, is due to report in 2022 but will lack detailed hepatic outcomes.
In this study, patients in the liraglutide arm lost 3.6 kg, with associated benefit in decreased liver fat and visceral fat. Somewhat surprisingly, sitagliptin-treated patients lost 1.7 kg, while glargine-treated patients lost 1.2 kg. Reduction in MRI-PDFF was −4% for liraglutide, −3.8% for sitagliptin, and −0.8% for glargine. Adjusting for pairwise comparisons among three groups, the appropriate threshold of statistical significance, a P-value of 0.0167 (0.05/3), showed that few outcomes differed by treatment. However, differences in weight and visceral adipose tissue were statistically significantly different among arms. The strength of this study is the detailed metabolic and hepatic outcomes, which provide important, detailed information and suggest that clinically significant weight loss is associated with a decrease in intrahepatic lipid; this effect was observed most strongly among those assigned to liraglutide.