Luseogliflozin, A Sodium Glucose Co-transporter 2 Inhibitor, Alleviates Hepatic Impairment in Japanese Patients with Type 2 Diabetes

M. Kusunoki; Y. Natsume; D. Sato; H. Tsutsui; T. Miyata; K. Tsutsumi; T. Suga; Y. Oshida

doi:10.1055/s-0042-111515

Drug Research, Table of Contents

Drug Res (Stuttg) 2016; 66(11): 603-606
DOI: 10.1055/s-0042-111515

Original Article

Luseogliflozin, A Sodium Glucose Co-transporter 2 Inhibitor, Alleviates Hepatic Impairment in Japanese Patients with Type 2 Diabetes

M. Kusunoki

¹Research Center of Health, Physical Fitness and Sports, Nagoya University, Nagoya, Japan

,

Y. Natsume

¹Research Center of Health, Physical Fitness and Sports, Nagoya University, Nagoya, Japan

,

D. Sato

²Graduate School of Medical Science, Yamagata University, Yamagata, Japan

,

H. Tsutsui

³General Medical Education Center of Teikyo University, Tokyo, Japan

,

T. Miyata

⁴Vascular Center, Sanno Medical Center, Tokyo, Japan

,

K. Tsutsumi

⁵Okinaka Memorial Institute for Medical Research, Tokyo, Japan

,

T. Suga

⁶Akishima Clinic, Nagoya, Japan

,

Y. Oshida

¹Research Center of Health, Physical Fitness and Sports, Nagoya University, Nagoya, Japan

› Author Affiliations

Abstract

Luseogliflozin, a selective inhibitor of sodium glucose co-transporter 2 (SGLT2), was previously shown to improve the blood glucose and hemoglobin A1c (HbA1c) levels of patients with type 2 diabetes in a clinical setting. Although patients with type 2 diabetes often have hepatic impairment, few reports have been published concerning the influence of luseogliflozin on HbA1c and hepatic function in patients with type 2 diabetes accompanied by hepatic impairment. The present study was undertaken to evaluate the influence of luseogliflozin on HbA1c and hepatic function in patients with type 2 diabetes divided into 2 groups according to hepatic function parameters (a normal group and an elevated group). In this study, luseogliflozin significantly improved both HbA1c and body weight to similar extents in both the normal group and the elevated group, accompanied by marked reductions in the aspartate aminotransferase (AST), alanine aminotransferase (ALT), and γ-glutamyl transpeptidase (γ-GTP) levels. These results suggested that luseogliflozin can be safely used in patients with type 2 diabetes who also exhibit hepatic impairment. The results additionally suggest the possibility that luseogliflozin might be capable of alleviating hepatic impairment in patients with type 2 diabetes.

Key words

type 2 diabetes - sodium glucose co-transporter 2 inhibitor - hepatic function

Full Text

References

References
1 Wright EM. Glucose transport families SLC5 and SLC50. Mol Aspects Med 2013; 34: 183-196
2 Wright EM, Loo DD, Hirayama BA. Biology of human sodium glucose transporters. Physiol Rev 2011; 91: 733-794
3 DeFronzo RA, Davidson JA, Del Prato S. The role of the kidneys in glucose homeostasis: a new path towards normalizing glycaemia. Diabetes Obes Metab 2012; 14: 5-14
4 Seino Y, Fukatsu A, Ubukata M et al. Efficacy and safety of luseogliflozin as monotherapy in Japanese patients with type 2 diabetes mellitus: a randomized, double-blind, placebo-controlled, phase 3 study. Curr Med Res Opin 2014; 30: 1245-1255
5 Zinman B, Wanner C, Lachin JM et al. EMPA-REG OUTCOME Investigators. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med 2015; 373: 2117-2128
6 Bhatt HB, Smith RJ. Fatty liver disease in diabetes mellitus. Hepatobiliary Surg Nutr 2015; 4: 101-108
7 Liang Y, Arakawa K, Ueta K et al. Effect of canagliflozin on renal threshold for glucose, glycemia, and body weight in normal and diabetic animal models. PLos One 2012; 7: e30555
8 Firneisz G. Non-alcoholic fatty liver disease and type 2 diabetes mellitus: the liver disease of our age?. World J Gastroenterol 2014; 20: 9072-9089
9 Le TA, Loomba R. Management of non-alcoholic fatty liver disease and steatohepatitis. J Clin Exp Hepatol 2012; 2: 156-173
10 Kusunoki M, Tsutsumi K, Inoue Y et al. Lipoprotein lipase activator NO-1886 improves fatty liver caused by high-fat feeding in streptozotocin-induced diabetic rats. Metabolism 2004; 53: 260-263
11 Suzuki M, Takeda M, Kito A et al. Tofogliflozin, a sodium/glucose cotrasporter 2 inhibitor, attenuates body weight gain and fat accumulation in diabetic and obese animal models. Nutr Diabetes 2014; 4: e125
12 Hayashizaki-Someya Y, Kurosaki E, Takasu T et al. Ipragliflozin, and fibrosis induced by choline-deficient 1-amino acid-defined diet in rats. Eur J Pharmacol 2015; 754: 19-24
13 Tahara A, Kurosaki E, Yokono M et al. Effects of SGLT2 inhibitor ipragliflozin on hyperglycemia, hyperlipidemia, hepatic steatosis, oxidative stress, inflammation, and obesity in type 2 diabetic mice. Eur J Pharmacol 2013; 715: 246-255
14 Obata A, Kubota N, Kubota T et al. Tofogliflozin improves insulin resistance as well as glucose tolerance by ameliorating fatty liver and obesity. Diabetes 2013; 62 (Suppl. 01) A285-A286