Comparison of Ipragliflozin and Pioglitazone Effects on Nonalcoholic Fatty Liver Disease in Patients With Type 2 Diabetes: A Randomized, 24-Week, Open-Label, Active-Controlled Trial

Ito, Daisuke; Shimizu, Satoshi; Inoue, Ken‐ichiro; Saito, Daigo; Yanagisawa, Mitsuru; Inukai, Kouichi; Akiyama, Yuji; Morimoto, Yoshihiro; Noda, Mitsuhiko; Shimada, Akira

doi:10.2337/dc17-0518

Cited by 246 publications

(227 citation statements)

References 30 publications

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“…In humans, 2 pooled analyses reported a decrease in plasma aminotransferases with canagliflozin treatment that correlated with the magnitude of body weight loss. A reduction in ALT and/or IHTG has been reported in small, open‐label studies of 5‐ to 6‐months duration with luseogliflozin, ipragliflozin, and empagliflozin, associated with reductions in BMI, visceral fat, and HbA1c. Tobita et al showed additional improvement in histology in a small, uncontrolled study in patients with biopsy‐proven NASH .…”

Section: Discussionmentioning

confidence: 86%

Effect of canagliflozin treatment on hepatic triglyceride content and glucose metabolism in patients with type 2 diabetes

Cusi

Bril

Barb

et al. 2018

Diabetes Obesity Metabolism

146

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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% AE 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 ≤ 0.001). A numerically larger absolute decrease in IHTG occurred with canagliflozin (−4.6% [−6.4; −2.7]) versus placebo (−2.4% [−4.2; −0.6]; P = 0.09). In patients withnon-alcoholic fatty liver disease (n = 37), the decrease in IHTG was −6.9% (−9.5; −4.2) versus −3.8% (−6.3; −1.3; P = 0.05), and strongly correlated with the magnitude of weight loss (r = 0.69, P < 0.001). Body weight loss ≥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. K E Y W O R D Sfatty, liver, canagliflozin, insulin resistance, insulin secretion, liver, randomized trial

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Section: Discussionmentioning

confidence: 86%

Effect of canagliflozin treatment on hepatic triglyceride content and glucose metabolism in patients with type 2 diabetes

Cusi

Bril

Barb

et al. 2018

Diabetes Obesity Metabolism

146

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“…We demonstrated significant improvement in CAP (an indicator of hepatic steatosis) in the dapagliflozin group after 24 weeks of treatment, while there was no improvement in the control group, and the percent reduction in CAP from baseline to 24 weeks was significantly larger in the dapagliflozin group than in the control group. There has only been two previous prospective investigations into the effect of SGLT2 inhibitors on hepatic steatosis that employed imaging methods such as CT and MRI . In the present study, we investigated the effect of dapagliflozin by measuring CAP, a new quantitative index of hepatic steatosis .…”

Section: Discussionmentioning

confidence: 98%

Evaluation of the effects of dapagliflozin, a sodium‐glucose co‐transporter‐2 inhibitor, on hepatic steatosis and fibrosis using transient elastography in patients with type 2 diabetes and non‐alcoholic fatty liver disease

Shimizu

Suzuki²,

Kato

et al. 2018

Diabetes Obesity Metabolism

281

219

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Based on these findings, the sodium-glucose co-transporter-2 inhibitor dapagliflozin improves liver steatosis in patients with type 2 diabetes and NAFLD, and attenuates liver fibrosis only in patients with significant liver fibrosis, although the possibility cannot be excluded that a reduction in body weight or visceral adipose tissue by dapagliflozin may be associated with a decrease of liver steatosis or fibrosis.

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“…As for a hypocaloric diet, a study showed that a 6% reduction in BM by a 3‐month hypocaloric diet was accompanied with a significant reduction in intrahepatic lipid content. Previous studies have suggested that ipragliflozin ameliorates hepatic fibrosis, insulin resistance and lipotoxicity in animal models, and reduces BM and visceral fat volume more effectively than pioglitazone in type 2 diabetes mellitus patients. In addition, recent studies suggested that while SGLT2i alone improves NASH, SGLT2i in combination with incretin‐based treatment, such as dipeptidyl peptidase‐4 inhibitor or glucagon‐like peptide‐1 analogs, can synergistically ameliorates NASH.…”

Section: Discussionmentioning

confidence: 99%

“…Ipragliflozin reduces plasma lipid levels and ameliorates liver steatosis in diabetic animal models. In type 2 diabetes mellitus patients, it decreases serum liver enzymes, visceral and subcutaneous fat volumes, and liver‐to‐spleen attenuation ratio on computed tomography after 24 weeks of therapy. Canagliflozin also improves liver function, and reduces hemoglobin A1c (HbA1c) and body mass.…”

Section: Introductionmentioning

confidence: 99%

Effects of canagliflozin on body composition and hepatic fat content in type 2 diabetes patients with non‐alcoholic fatty liver disease

Inoue

Hayashi

Taguchi

et al. 2019

J of Diabetes Invest

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Aims/Introduction Non‐alcoholic fatty liver disease is frequently associated with type 2 diabetes, and constitutes an important risk factor for the development of hepatic fibrosis and hepatocellular carcinoma. Because there remains no effective drug therapy for non‐alcoholic fatty liver disease associated with type 2 diabetes, we evaluated the efficacy of sodium–glucose cotransporter 2 inhibitor. Methods and Materials In the present pilot, prospective, non‐randomized, open‐label, single‐arm study, we evaluated the effect of 100 mg canagliflozin administered once daily for 12 months on serological markers, body composition measured by bioelectrical impedance analysis method and hepatic fat fraction measured by magnetic resonance imaging in type 2 diabetes patients with non‐alcoholic fatty liver disease . Results Canagliflozin significantly reduced body and fat mass, and induced a slight decrease in lean body or muscle mass that did not reach significance at 6 and 12 months. Reductions in fat mass in each body segment (trunk, arms and legs) were evident, whereas those in lean body mass were not. The hepatic fat fraction was reduced from a baseline of 17.6 ± 7.5% to 12.0 ± 4.6% after 6 months and 12.1 ± 6.1% after 12 months ( P < 0.0005 and P < 0.005), whereas serum liver enzymes and type IV collagen concentrations improved. From a mean baseline hemoglobin A1c of 8.7 ± 1.4%, canagliflozin significantly reduced hemoglobin A1c after 6 and 12 months to 7.3 ± 0.6% and 7.7 ± 0.7% ( P < 0.0005 and P < 0.01). Conclusions Canagliflozin reduced body mass, fat mass and hepatic fat content without significantly reducing muscle mass.

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Comparison of Ipragliflozin and Pioglitazone Effects on Nonalcoholic Fatty Liver Disease in Patients With Type 2 Diabetes: A Randomized, 24-Week, Open-Label, Active-Controlled Trial

Abstract: Compared with pioglitazone, ipragliflozin exerts equally beneficial effects on NAFLD and glycemic control during the treatment of patients with type 2 diabetes complicated by NAFLD. Furthermore, ipragliflozin significantly reduced body weight and abdominal fat area.

Cited by 246 publications

References 30 publications

Effect of canagliflozin treatment on hepatic triglyceride content and glucose metabolism in patients with type 2 diabetes

Effect of canagliflozin treatment on hepatic triglyceride content and glucose metabolism in patients with type 2 diabetes

Evaluation of the effects of dapagliflozin, a sodium‐glucose co‐transporter‐2 inhibitor, on hepatic steatosis and fibrosis using transient elastography in patients with type 2 diabetes and non‐alcoholic fatty liver disease

Effects of canagliflozin on body composition and hepatic fat content in type 2 diabetes patients with non‐alcoholic fatty liver disease

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