PMID- 30447037 OWN - NLM STAT- MEDLINE DCOM- 20200907 LR - 20221207 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 21 IP - 4 DP - 2019 Apr TI - Effect of canagliflozin treatment on hepatic triglyceride content and glucose metabolism in patients with type 2 diabetes. PG - 812-821 LID - 10.1111/dom.13584 [doi] AB - AIM: To evaluate the impact of the sodium glucose co-transporter 2 inhibitor canagliflozin on intrahepatic triglyceride (IHTG) accumulation and its relationship to changes in body weight and glucose metabolism. MATERIALS AND METHODS: In this double-blind, parallel-group, placebo-controlled, 24-week trial subjects with inadequately controlled type 2 diabetes mellitus (T2DM; HbA1c = 7.7% +/- 0.7%) from two centres were randomly assigned (1:1) to canagliflozin 300 mg or placebo. We measured IHTG by proton-magnetic resonance spectroscopy (primary outcome), hepatic/muscle/adipose tissue insulin sensitivity during a 2-step euglycaemic insulin clamp, and beta-cell function during a mixed meal tolerance test. Analyses were per protocol. RESULTS: Between 8 September 2014-13 June 2016, 56 patients were enrolled. Canagliflozin reduced HbA1c (placebo-subtracted change: -0.71% [-1.08; -0.33]) and body weight (-3.4% [-5.4; -1.4]; both P /=5% with a >/=30% relative reduction in IHTG occurred more often with canagliflozin (38% vs. 7%, P = 0.009). Hepatic insulin sensitivity improved with canagliflozin (P < 0.01), but not muscle or adipose tissue insulin sensitivity. Beta-cell glucose sensitivity, insulin clearance, and disposition index improved more with canagliflozin (P < 0.05). CONCLUSIONS: Canagliflozin improves hepatic insulin sensitivity and insulin secretion and clearance in patients with T2DM. IHTG decreases in proportion to the magnitude of body weight loss, which tended to be greater and occur more often with canagliflozin. CI - (c) 2018 John Wiley & Sons Ltd. FAU - Cusi, Kenneth AU - Cusi K AUID- ORCID: 0000-0002-8629-418X AD - Division of Endocrinology, Diabetes and Metabolism, University of Florida, Gainesville, Florida. AD - Malcom Randall Veterans Administration Medical Center, Gainesville, Florida. FAU - Bril, Fernando AU - Bril F AD - Division of Endocrinology, Diabetes and Metabolism, University of Florida, Gainesville, Florida. FAU - Barb, Diana AU - Barb D AD - Division of Endocrinology, Diabetes and Metabolism, University of Florida, Gainesville, Florida. FAU - Polidori, David AU - Polidori D AUID- ORCID: 0000-0002-8427-5663 AD - Janssen Research & Development, LLC, San Diego, California. FAU - Sha, Sue AU - Sha S AD - Janssen Research & Development, LLC, Raritan, New Jersey. FAU - Ghosh, Atalanta AU - Ghosh A AD - Janssen Research & Development, LLC, Raritan, New Jersey. FAU - Farrell, Kristin AU - Farrell K AD - Janssen Research & Development, LLC, Raritan, New Jersey. FAU - Sunny, Nishanth E AU - Sunny NE AD - Division of Endocrinology, Diabetes and Metabolism, University of Florida, Gainesville, Florida. FAU - Kalavalapalli, Srilaxmi AU - Kalavalapalli S AD - Division of Endocrinology, Diabetes and Metabolism, University of Florida, Gainesville, Florida. FAU - Pettus, Jeremy AU - Pettus J AUID- ORCID: 0000-0002-5999-0091 AD - VA San Diego Healthcare System and Department of Medicine, Division of Endocrinology and Metabolism, University of California, San Diego, California. FAU - Ciaraldi, Theodore P AU - Ciaraldi TP AD - VA San Diego Healthcare System and Department of Medicine, Division of Endocrinology and Metabolism, University of California, San Diego, California. FAU - Mudaliar, Sunder AU - Mudaliar S AD - VA San Diego Healthcare System and Department of Medicine, Division of Endocrinology and Metabolism, University of California, San Diego, California. FAU - Henry, Robert R AU - Henry RR AUID- ORCID: 0000-0002-4821-0117 AD - VA San Diego Healthcare System and Department of Medicine, Division of Endocrinology and Metabolism, University of California, San Diego, California. LA - eng GR - S10 OD021726/OD/NIH HHS/United States PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20181218 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Glycated Hemoglobin A) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Triglycerides) RN - 0 (hemoglobin A1c protein, human) RN - 0SAC974Z85 (Canagliflozin) SB - IM MH - Aged MH - Canagliflozin/*therapeutic use MH - Diabetes Mellitus, Type 2/*drug therapy/metabolism MH - Double-Blind Method MH - Female MH - Glucose Clamp Technique MH - Glycated Hemoglobin/metabolism MH - Humans MH - *Insulin Resistance MH - *Insulin Secretion MH - Insulin-Secreting Cells/*metabolism MH - Liver/*metabolism MH - Male MH - Middle Aged MH - Proton Magnetic Resonance Spectroscopy MH - Sodium-Glucose Transporter 2 Inhibitors/*therapeutic use MH - Treatment Outcome MH - Triglycerides/*metabolism MH - Weight Loss OTO - NOTNLM OT - canagliflozin OT - fatty OT - insulin resistance OT - insulin secretion OT - liver OT - randomized trial EDAT- 2018/11/18 06:00 MHDA- 2020/09/08 06:00 CRDT- 2018/11/18 06:00 PHST- 2018/09/17 00:00 [received] PHST- 2018/11/06 00:00 [revised] PHST- 2018/11/14 00:00 [accepted] PHST- 2018/11/18 06:00 [pubmed] PHST- 2020/09/08 06:00 [medline] PHST- 2018/11/18 06:00 [entrez] AID - 10.1111/dom.13584 [doi] PST - ppublish SO - Diabetes Obes Metab. 2019 Apr;21(4):812-821. doi: 10.1111/dom.13584. Epub 2018 Dec 18.