Ipragliflozin, a SGLT2 Inhibitor, Reduced Body Weight and Fat Mass but Not Muscle Mass in Japanese Type 2 Diabetic Patients Treated with Insulin—A Randomized Clinical Trial

Morino, Katsutaro; Inoue, Hideka; Fuse, Katsuo; Tanaka, Sachiko; Kondo, Keiko; Arima, Hisatomi; Miura, Katsuyuki; Sato, Daisuke; Ohashi, Nobuhide; Ida, Shogo; Miyazawa, Itsuko; Sato, Osamu; Ugi, Satoshi; Maegawa, Hiroshi

doi:10.2337/db18-1199-p

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“…Addressing such a knowledge gap is essential to elucidate some of the untangled observations in previous studies. For example, preserved lean mass following SGLT2i treatment (Obata et al 2016, Morino et al 2018) cannot be explained by a reduction of insulin levels but may be rationalised by the protein-preserving effect of GH. Furthermore, a close evaluation of insulin and GH in obesity may further provide mechanistic insights into potential anti-obesity targets in the modulation of metabolism and body composition.…”

Section: Introductionmentioning

confidence: 99%

Dapagliflozin restores insulin and growth hormone secretion in obese mice

Huang

Wang

et al. 2020

Journal of Endocrinology

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The well-documented hormonal disturbance in a general obese population is characterised by an increase in insulin secretion and a decrease in growth hormone (GH) secretion. Such hormonal disturbance promotes an increase in fat mass, which deteriorates obesity and accelerates the development of insulin resistance and type 2 diabetes. While the pathological consequence is alarming, the pharmaceutical approach attempting to correct such hormonal disturbance remains limited. By applying an emerging anti-diabetic drug, the sodium-glucose cotransporter 2 inhibitor, dapagliflozin (1 mg/kg/day for 10 weeks), to a hyperphagic obese mouse model, we observed a significant improvement in insulin and GH secretion as early as 4 weeks after the initiation of the treatment. Restoration of pathological disturbance of insulin and GH secretion reduced fat accumulation and preserved lean body mass in the obese animal model. Such phenotypic improvement followed with concurrent improvements in glucose and lipid metabolism, insulin sensitivity, as well as the expression of metabolic genes that were regulated by insulin and GH. In conclusion, 10 weeks of treatment with dapagliflozin effectively reduces hyperinsulinemia and restores pulsatile GH secretion in the hyperphagic obese mice with considerable improvement in lipid and glucose metabolism. Promising outcomes from this study may provide insights into drug intervention to correct hormonal disturbance in obesity to delay the diabetes progression.

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Section: Introductionmentioning

confidence: 99%