1865-P: SGLT2 Inhibition Compared with Iso-energetic/Low-Carbohydrate Diet Reprograms Systemic Substrate Oxidation in Type 2 Diabetes

Abstract

Introduction: Pharmacologic inhibition of the renal sodium/glucose cotransporter-2 (SGLT2i) facilitates lipid oxidation. Iso-energetic/low-carbohydrate diet (i-Carbo) eliminates the same amount of glucose as SGLT2 inhibition (∼ 50 g/day of glucose). We examined whether i-Carbo and SGLT2i may have any impact, on 1) fasting and postprandial energy expenditure (EE) and substrate oxidation, 2) the basal-bolus dose of insulin that achieve euglycemia. Method: Twenty four T2D (M/F = 15/9, age 53.6 ± 14.2, BMI 26.9 ± 4.8 kg/m2, HbA1c 12.5 ± 1.6 %) were enrolled to this 12 weeks, randomized, 3 arms open-label, prospective study with basal-bolus insulin titration algorithm, control diet (CON) or adding canagliflozin 100 mg/day to CON (SGLT2i) and the i-Carbo. We measured indirect calorimetry to provide EE and respiratory quotient (RQ) during fasting and postprandial before and after the intervention. Results: In spite of similar carbohydrate amount in the i-Carbo, compared to the SGLT2i, the total daily dose of insulin was significantly higher (p=0.02). Compared to the CON, fasting EE were similar on both SGLT2i and i-Carbo, however, postprandial EE were elevated, respectively (p=0.03, 0.04). Fasting RQ was marginally higher in SGLT2i compared to the CON (p=0.049). Postprandial RQ was elevated by means of increased carbohydrate substrate utilization on both SGLT2i (p=0.04) and i-Carbo (p=0.03) groups compared to the CON. Conclusion: Iso-energetic/low-carbohydrate in i-Carbo, which matches urinary carbohydrate loss in SGLT2i, had similar fasting and postprandial energy expenditure and substrate oxidation rate. Increased insulin requirement in i-Carbo indicates that relative high lipid and protein ratio, compared to SGLT2i, may have any effect to insulin requirement. Disclosure H. Igarashi: None. H. Uchino: None. M. Furuta: None. M. Miyagi: None. N. Kumashiro: Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc. Speaker’s Bureau; Self; Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited. T. Hirose: Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo, Mitsubishi Tanabe Pharma Corporation, Ono Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited. Speaker’s Bureau; Self; AstraZeneca, Lilly Diabetes, Novo Nordisk Inc., Sanofi, Sumitomo Dainippon Pharma Co., Ltd.