bluuebunny/crossref_metadata_2025_split huggingface dataset:
Apabetalone (RVX-208) Lowers Major Adverse Cardiovascular Events (MACE) in Diabetes Mellitus Patients with CVD by Attenuating Monocyte Adhesion to Endothelial Cells
Authors: TSUJIKAWA LAURA , KULIKOWSKI EWELINA , CALOSING CYRUS , WASIAK SYLWIA , GILHAM DEAN , HALLIDAY CHRISTOPHER , JOHANSSON JAN O. , SWEENEY MICHAEL , WONG NORMAN C. 
Published: June 2018

Apabetalone (RVX-208) leads to a 57% relative risk reduction of MACE in patients with diabetes mellitus (DM) and CVD. To test whether RVX-208, an inhibitor (BETi) of epigenetic readers bromodomain extra-terminal (BET) proteins lowers CVD by affecting genes mediating monocyte adhesion to endothelial cells in response to high glucose(HG) and dietary metabolite trimethyl-amine oxide (TMAO). Cultured THP-1 monocytes, HUVEC endothelial cells and primary human hepatocytes (PHH) were exposed to varying amts of glucose and TMAO. Results showed that HG (25.6 mM) induced Very Late Antigen-4 (VLA-4) mRNA, a gene mediating THP-1 adhesion by 1.3-fold and RVX-2suppressed it &gt;50%. BETi blocked TMAO induction of VLA-4 mRNA by &gt;50% in THP-1. In HUVECs RVX-2abrogated HG induction of E-selectin and MYD88 mRNA by 2- and 1.3-fold, respectively and lowered TMAO induction of both mRNAs by &gt;50%. Microbiome action on dietary phospholipids followed by hepatic flavin mono-oxygenase-3 (FMO3) processing yields TMAO. In PHH exposed for 24 hours to RVX-208, FMO3 mRNA was lower by 40% but it also suppressed a transcriptional regulator of FMO3, farnesoid X receptor (FXR). BETi for 6 hours suppressed both FXR mRNA and protein within 6 hours by &gt;80% suggesting a direct effect of BETi on the FXR gene. Furthermore, in ChiP assays BRD4, a BET protein, dissociated immediately from FXR DNA upon exposure to RVX-208. BRD4 guides a complex containing RNA pol II along active genes, its dissociation would halt transcription of the gene.
In summary, Apabetalone inhibits HG and TMAO enhanced adhesion of THP-1 to HUVECs, this process mimics a step in CVD pathogenesis. RVX-2suppresses cellular adhesion genes; VLA-4 in THP-1 and both E-selectin plus MYD88 in HUVECs. BETi blocks TMAO activity and its production by inhibiting FXR expression, a regulator of FMO3 gene transcription. Rapid actions of BETi in dissociating BRD4 from FXR DNA suggests a direct effect of RVX-2on transcription of this gene.

Disclosure
L. Tsujikawa: None. E. Kulikowski: Employee; Self; Resverlogix Corp.. C. Calosing: None. S. Wasiak: Employee; Self; Resverlogix Corp. D. Gilham: Employee; Self; Resverlogix Corp.. Stock/Shareholder; Self; Resverlogix Corp.. C. Halliday: None. J.O. Johansson: Employee; Self; Resverlogix Corp., Artery Therapeutics, Inc. M. Sweeney: Employee; Self; Resverlogix Corp. N.C. Wong: Stock/Shareholder; Self; Resverlogix Corp..
The Effect of Gliptins to Improve Functional Outcome after Stroke in Mice Is Mediated by the CXCR4/SDF-1α Pathway
Authors: CHIAZZA FAUSTO , TAMMEN HARALD , PINTANA HIRANYA , LIETZAU GRAZYNA , COLLINO MASSIMO , NYSTROM THOMAS , KLEIN THOMAS , DARSALIA VLADIMER , PATRONE CESARE 
Published: June 2018

Dipeptidyl peptidase-4 (DPP-4) inhibitors (gliptins) decrease hyperglycemia by inhibiting glucagon-like peptide-1 (GLP-1) cleavage. Gliptins can also improve stroke outcome in rodents independently of GLP-1R. However, the underlying mechanisms are unknown. Stromal cell-derived factor-1α (SDF-1α) is a DPP-4 substrate and CXCR4 agonist that promotes beneficial effects in injured brains. However, SDF-1α involvement in gliptin-mediated neuroprotection is unproven. We aimed to determine whether gliptins improve stroke outcome via SDF-1α/CXCR4 and identify additional targets behind the efficacy. Adult, male C57bl6/j mice (n=101) underwent transient focal cerebral ischemia. Linagliptin was administered for 3 days or 3 weeks. The CXCR4-antagonist AMD3100 was administered starting a day before ischemia. Stroke outcome was assessed by measuring upper-limb function and brain tissue damage. Levels of active GLP-1, gastric inhibitory polypeptide (GIP) and SDF-1α were quantified by ELISA in serum and brain. Mass spectrometry was used to identify additional gliptin-mediated effectors in brain tissue samples. Sustained, post-ischemic treatment with linagliptin reduced motor impairment (p003C0.01) and tissue damage (p003C0.05). Linagliptin increased serum levels of GLP-1 (p003C0.0001), GIP (p003C0.05) and SDF-1α (p003C0.05). However, only SDF-1α levels were increased in the brain (p003C0.001). Linagliptin also decreased the presence of neurogranin-derived peptides and peptides from an isoform of myelin basic protein (MBG, p003C0.05). The inhibition of SDF-1α/CXCR4 pathway diminished the positive effects of linagliptin on stroke outcome (not different from vehicle). We propose a gliptin-mediated neuroprotective mechanism via SDF-1α, which could affect Ca2+ homeostasis, altering neurogranin and MBG processing and potentially decreasing calpain activity. These results provide new insights into restorative gliptin-mediated effects against stroke.

Disclosure
F. Chiazza: Other Relationship; Self; Boehringer Ingelheim GmbH. H. Tammen: Consultant; Self; Boehringer Ingelheim GmbH. H. Pintana: Other Relationship; Self; Boehringer Ingelheim GmbH. G. Lietzau: Other Relationship; Self; Boehringer Ingelheim GmbH. M. Collino: None. T. Nystrom: Research Support; Self; AstraZeneca. Advisory Panel; Self; Eli Lilly and Company, Novo Nordisk A/S. Speaker's Bureau; Self; Boehringer Ingelheim GmbH. T. Klein: Employee; Self; Boehringer Ingelheim GmbH. V. Darsalia: Other Relationship; Self; Boehringer Ingelheim GmbH. C. Patrone: Other Relationship; Self; Boehringer Ingelheim GmbH.
The Novel Use of Nanotechnology Structured Water Magnalife to Control Blood Glucose Level in Type 2 Diabetic Patients
Authors: SAMI ALI K.M. , AMIN KAWA H. , KURMANJI MOHAMMED T. 
Published: June 2018

Introduction: Nanotechnology structured water is a new type of water that is produced using special modulators to change and add new properties to water molecules.
Objectives: To find out the effect of drinking nanotechnology structured water on blood glucose levels in patients with type 2 diabetes mellitus.
Patients and Methods: Type-2 diabetes mellitus patients (n=387) with only oral hypoglycemic drugs were blindly divided into 2 groups. Group A (191 patients) supplied with nanotechnology structured water and group B (196 patients) supplied with ordinary bottled water. Water bottles were unlabeled and patients were unaware of the type of water given to them. Blood glucose level was measured as Glycated Hemoglobin (HbA1c) in the same laboratory. Tests were done before starting drinking the water given to the patients as baseline then measured at the end of the third month of drinking the given water in a daily dose of (500 ml /25 kg of body weight).
Results: At the end of the the study, only 352 patients were followed (35 patients dropped out for different reasons). Group A (n=183) (aged 24 to 76, mean 50.2) years with male to female (56.3%: 43.7%), and group B (n=169) (aged 30 to77, mean49.3) years with male to female (49.1%:50.9%). Group A showed significant difference between baseline HbA1c 8.1%+/-1.38 vs. HbA1c after 3 months 6.6%+/-0.85 (p&lt;0.001). While group B showed no significant difference in pre-post HbA1c tests 7.9% +/-1.36 vs. 7.8% +/-1.16 (p=0.274). The percentage of Patients with HbA1c&lt;7 in group A increased from (25.1%) at baseline to (61.2%) after 3 months, while in group B, the percentage of patients with HbA1c &lt;7 decreased from (27.2%) to (19.5%).
Conclusion: Nanotechnology structured water magnalife offers a new way to achieve better control of blood sugar in type 2 diabetic patients. However, further studies are needed to study the long term use of nano-water for the possibility to gradually decrease the needed doses of hypoglycemic agents or to stop them.

Disclosure
A.K. M. Sami: None. K.H. Amin: None. M.T. Kurmanji: None.
Central Obesity but Not BMI Related to Hypoglycemic Efficacy of Metformin—Subanalysis of MARCH Study
Authors: YANG ZHAOJUN , WANG XIN , WANG NA , JIN XIAN , ZHANG JINPING , ZHANG XUELIAN , YANG WENYING 
Published: June 2018

Objective: MARCH study(Metformin and AcaRbose in Chinese as the initial Hypoglycaemic treatment) was a nationwide, multicenter, randomized controlled trial in China (Chinese Clinical Trial Registry, number ChiCTR-TRC-08000231), and confirmed that Acarbose was non-inferior to Metformin in terms of hypoglycemic effectiveness among Chinese patients with newly-diagnosed type 2 diabetes. The purpose of this paper was to understand the association between the efficacy of Acarbose and Metformin and the parameters reflected body weight.
Method: A total of 788 participants from MARCH database were included in this analysis. The participants were divided into four BMI groups(BMI 19-23.9, 24-25.9, 26-27.9, and 28-30kg/m2) and four weight loss groups according to quartile of weight change from the baseline, and two central obesity groups according to IDF criteria(i.e., waist circumference &gt;=90cm in male, &gt;=80cm in female), respectively. ANCOVA was used to assess the association of the above obesity categories with the changes of HbA1c from baseline in Acarbose group and Metformin group respectively, with treatment and center as factors, and baseline HbA1c as a covariate.
Result: There was no significant difference in change from baseline HbA1c within the acarbose group (0.98%,0.95%,1.20%,1.14%,p=0.1476) as well as the metformin group (1.08%,1.12%,1.20%,1.32%,p=0.2918) when patients were stratified by BMI quartile. The reduction in HbA1c was greater in patients with central obesity than those without in Metformin treatment group[1.26%(95% CI:1.15%-1.37%) vs.0.98%(95% CI:0.81%-1.15%),p=0.0059], but there was no significant difference among patients with and without central obesity for HbA1c reduction in acarbose treatment group[1.10%(95% CI:0.98%-1.21%) vs. 0.97%(95% CI:0.81%-1.13%),p=0.2037].
Conclusion: The hypoglycemic efficacy of acarbose is not associated with the obesity status. In contrast, Metformin was more effective in patients with central obesity.

Disclosure
Z. Yang: None. X. Wang: None. N. Wang: None. X. Jin: None. J. Zhang: None. X. Zhang: None. W. Yang: None.
An Observational Study to Evaluate Change in Dose Requirement of Standard Glucose Lowering, Lipid Lowering, and Antihypertensive Therapy Treated with SGLT2 Inhibitor (Canagliflozin) over One Year, in Fifty T2DM Patients
Authors: GUPTA VISHAL , TELI VAISHALI 
Published: June 2018

Objective: To evaluate effect of Canagliflozin (CA) on dose of other commonly co-administered antidiabetic, antihypertensive (AH) and lipid lowering drugs (AL) over a period of 12 months.
Methodology: Fifty diabetes patients receiving glucose lowering therapy, AH and LL were treated with CA for a period of 12months. These patients were followed up at months 3, 6 and 12 for routine metabolic assessment and subsequent amendment in drug therapy. In the present study we evaluated the change in doses of background antidiabetic, AH and AL medication 12 months after CA therapy. Data was represented as Mean + 2 SD with 95% CI, a p value of 0.or lower was considered significant. Paired t test was used to compare average dose of all drug classes at baseline and end of 12 months.
Results: There was a significant reduction in average dose of Gliclazide from 172.5 ± 62.16mg at baseline to 141.25 ± 64.24mg at the end of 12 month (p= 0.05) The average dose of metformin reduced from 1.19 ± 0.53g at baseline (BS) to 1.± 0.51g at the end of 12 month (p= 0.18, not significant NS), Sitagliptin was reduced from 75.78 ± 26.56mg at BS to 75 ± 29.09mg at the end of 12 month (p= 0.91, NS). Basal insulin reduced from 27.14 ± 14.46IU at BS to 25.85 ± 28.63IU at the end of 12 month (p= 0.91, NS) Rosuvastatin slightly increased from 19.16 ± 4.53mg at BS to 19.79 ± 6.35mg at the end of 12 month (p= 0.57, NS) Among AH therapy, average dose of Telmisartan reduced from 43.33 ± 23.94mg at BS to 37.61 ± 22.39mg at the end of 12 month (p= 0.42, NS), Valsartan reduced from 103.33 ± 52.45mg at BS to 93.33 ± 54.82mg at the end of 12 month (p= 0.65, NS) and Cilnidipine reduced from 15 ± 5.27mg at BS to 17 ± 11.59mg at the end of 12 month (p= 0.62, NS).
Conclusion: Canagliflozin was associated with reduced requirements of gliclazide after one year of therapy in type 2 diabetes patients.

Disclosure
V. Gupta: None. V. Teli: None.
Assessment of Adverse Renal Effects in Patients with Type 2 Diabetes Mellitus (T2DM) Receiving Ertugliflozin
Authors: PATEL SHRITA M. , HICKMAN MARY A. , FREDERICH ROBERT , LAURING BRETT , TERRA STEVEN , JOHNSON SUSAN L. , HUYCK SUSAN , MANCUSO JAMES P. 
Published: June 2018

Ertugliflozin (ERTU) is a SGLT2 inhibitor for the treatment of T2DM. Adverse renal effects were assessed in adults with T2DM receiving ERTU relative to placebo (PBO) or active comparators in pooled analyses of 7 randomized, double-blind, Phase 3 trials. Patients (N=4859) received ERTU 5 mg (n=1716), ERTU 15 mg (n=1693), or non-ERTU (PBO, glimepiride or sitagliptin; n=1450) for up to 2 years. Mean age was 57.8 years, 25.8% were ≥65 years old and 51.8% were males. Mean eGFR was 85.3 mL/min/1.73 m2 and ∼12% had moderate renal impairment (RI; eGFR &lt;60 mL/min/1.73 m2). The mean duration of T2DM was 7.9 years and mean baseline A1C was 8.2%.
The incidence of renal-related AEs was low across the groups (ERTU 5 mg, 0.6%; ERTU 15 mg, 0.8%; non-ERTU, 0.4%); few were serious (0.1% in all groups) or led to treatment discontinuation (0.1%, 0.2% and 0.1%, respectively). Subgroup analyses demonstrated that in patients with moderate RI, renal-related AEs were more frequent in the ERTU groups relative to the non-ERTU group (ERTU 5 mg, 3.6%; ERTU 15 mg, 2.1%; non-ERTU, 1.1%). Incidence of renal-related AEs was similar across groups for patients ≥65 years old (excluding those with moderate RI at baseline) (ERTU 5 mg, 0.3%; ERTU 15 mg, 1.0%; non-ERTU, 0.8%) or those using diuretics (ERTU 5 mg, 1.2%; ERTU 15 mg, 0.8%; non-ERTU, 0.8%) or ACE/ARB (ERTU 5 mg, 0.9%; ERTU 15 mg, 0.9%; non-ERTU, 0.5%).
Independent blinded adjudication for causality was performed for pre-specified renal-related AEs and renal laboratory changes from baseline. Four patients had renal events that were adjudicated as causally related to study medication (“possible” or “very likely”; 1 in the ERTU 5 mg group, 2 in the ERTU 15 mg group and 1 in the non-ERTU group).
In conclusion, there was no increased risk of adverse renal effects in patients with T2DM receiving ERTU relative to PBO or active comparators, except in those with baseline moderate RI.

Disclosure
S.M. Patel: Employee; Self; Merck & Co., Inc.. Employee; Spouse/Partner; GlaxoSmithKline plc.. Stock/Shareholder; Self; Merck & Co., Inc.. Stock/Shareholder; Spouse/Partner; GlaxoSmithKline plc. M.A. Hickman: Employee; Self; Pfizer Inc.. Stock/Shareholder; Self; Pfizer Inc. R. Frederich: Employee; Self; Pfizer Inc.. Stock/Shareholder; Self; Pfizer Inc., Bristol-Myers Squibb Company. B. Lauring: Employee; Self; Merck & Co., Inc. S. Terra: Employee; Self; Pfizer Inc. S.L. Johnson: Employee; Self; Pfizer Inc. S. Huyck: Employee; Self; Merck & Co., Inc. J.P. Mancuso: Employee; Self; Pfizer Inc.. Stock/Shareholder; Self; Pfizer Inc.. Employee; Spouse/Partner; Pfizer Inc.. Stock/Shareholder; Spouse/Partner; Pfizer Inc..
Suppression of Ketogenesis in Type 1 Diabetes Is Not Delayed by SGLT2 Inhibitor Therapy
Authors: SIEBEL STEPHAN , PATEL NEHA S. , GALDERISI ALFONSO , CARRIA LORI R. , TAMBORLANE WILLIAM V. , SHERR JENNIFER 
Published: June 2018

Enthusiasm for SGLT2 inhibitors as adjunctive agents for T1D has been tempered by increased risk of DKA, especially in pump treated patients susceptible to interruptions of basal insulin due to infusion site failures. Our insulin interruption study showed that failure to recognize early metabolic decompensation in SGLT2i-treated T1D patients relates to blunted increases in plasma glucose (PG) rather than accelerated ketogenesis (Δ PG 99±13 vs. 197±24 mg/dL, p&lt;0.002; Δ free fatty acids [FFA] 0.8±0.1 vs. 0.7±0.1 and Δ β-hydroxy-butyrate [BHB] 1.5±0.2 vs. 1.2±0.2 mmol/L) before and after SGLT2i therapy. We report herein whether correction of early ketogenesis by a rescue dose of rapid-acting insulin is adversely affected by SGLT2i use. Ten adults [age 23±5 years, A1c 7.4±0.8%] had insulin interruption studies pre- and post 3 weeks of canagliflozin therapy. After a 6-hour suspension, a 0.2 unit/kg SQ bolus of aspart was given. PG, FFA and BHB levels were monitored for 150 minutes. PG fell from 314±42 to 183±17mg/dl pre- vs. 186±73 to 117±33mg/dL post SGLT2i use. The fall in FFA and BHB levels were unaffected by SGLT2i therapy(Figure). These data indicate that SGLT2i treatment does not impair suppression of increased FFA and BHB levels due to interruption of basal insulin infusion. Turning ketogenesis off, as well as on, does not appear to be affected by SGLT2i use.

Disclosure
S. Siebel: None. N.S. Patel: Consultant; Self; Janssen Pharmaceuticals, Inc.. A. Galderisi: None. L.R. Carria: None. W.V. Tamborlane: Consultant; Self; AstraZeneca, Boehringer Ingelheim GmbH, Eli Lilly and Company, Medtronic MiniMed, Inc., Novo Nordisk Inc., Sanofi, Takeda Pharmaceuticals U.S.A., Inc. J. Sherr: Consultant; Self; Medtronic MiniMed, Inc.. Advisory Panel; Self; Insulet Corporation, Eli Lilly and Company, Bigfoot Biomedical.
A Pilot, Head-to-Head Comparison of Hydroxychloroquine (HCQ) with Pioglitazone (PIO) as Third-Line Agents in Type 2 Diabetic Patients Failing Metformin and a Sulfonylurea (SU)
Authors: HSIA STANLEY H. , DURAN PETRA , DAVIDSON MAYER B. 
Published: June 2018

Type 2 diabetes is characterized by insulin resistance and inflammation. HCQ, a commonly used anti-inflammatory drug for rheumatoid arthritis and lupus, is associated with a lower risk of new-onset type 2 diabetes and reports of hypoglycemia in diabetic patients. PIO, an effective 3rd-line agent in patients failing metformin and SUs, has several side effects (e.g., weight gain, fluid retention, fractures) while HCQ has relatively few. We compared 15 patients taking HCQ 400 mg daily with 7 patients taking PIO 45 mg daily, with baseline HbA1c levels of 7.5-11.0% on maximum-tolerated doses of metformin and a SU, in a randomized controlled trial. Glucose control, insulin resistance, and inflammation (highly-sensitive C-reactive protein, hsCRP) were measured at baseline, 2 and 4 months.Results (Mean ± SD)MonthHbA1c (%)Weight (kg)Homeostasis Model Assessment (HOMA) % SensitivityhsCRP (mg/L)HCQPIOHCQPIOHCQPIOHCQPIO08.6 ± 1.09.1 ± 0.785.7 ± 14.383.7 ± 18.2109 ± 97102 ± 876.2 ± 6.78.8 ± 7.227.5 ± 0.96.8 ± 0.385.4 ± 13.986.2 ± 17.485 ± 61170 ± 1385.5 ± 5.92.2 ± 2.047.4 ± 0.96.3 ± 0.285.4 ± 14.587.0 ± 17.996 ± 74180 ± 1364.2 ± 3.83.3 ± 3.7pa&lt;0.0001&lt;0.00010.760.020.500.060.670.001pb0.00010.0040.010.054 a p value for the change from 0 to 4 months by 1-way repeated ANOVA; b p value for the difference between groups by 2-way repeated ANOVA.
Baseline characteristics were not significantly different between groups. Both drugs were well tolerated and significantly improved glucose control; PIO was more effective than HCQ but also caused significantly more weight gain. PIO increased insulin sensitivity while HCQ did not; PIO also significantly decreased hsCRP. HCQ may be beneficial in uncontrolled type 2 diabetic patients as a 3rd-line agent.

Disclosure
S.H. Hsia: Research Support; Self; AstraZeneca, Bayer AG, Bristol-Myers Squibb Company, Cirius Therapeutics, Eli Lilly and Company, Intarcia Therapeutics, Inc., Ionis Pharmaceuticals, Inc., Ligand Pharmaceuticals, Inc., Merck & Co., Inc., National Institute of General Medical Sciences, PhaseBio Pharmaceuticals, Inc., Sanofi-Aventis, TaiwanJ Pharmaceuticals Co., Ltd., Theracos, Inc., Tobira Therapeutics, VTV Therapeutics. P. Duran: None. M.B. Davidson: Employee; Self; Insulin Algorithms, Inc.
The Elevation of Hematocrit after Administration of SGLT2 Inhibitors Does Not Correlate with Plasma Osmolarity in Japanese Subjects with Type 2 Diabetes
Authors: WADA YOSHIHARU , HAMAMOTO YOSHIYUKI , IWASAKI YORIHIRO , NAKATANI YOSHIHISA , FUJIKAWA JUN , HONJO SACHIKO , AIZAWA-ABE MEGUMI , HAMASAKI AKIHIRO 
Published: June 2018

It has been reported that hematocrit is elevated after administration of sodium-glucose cotransporter 2 (SGLT2) inhibitors. However, it remains controversial whether this elevation is caused by its diuretic effect. In this study, we aimed to clarify the mechanism of hematocrit elevation by examining the correlation between hematocrit and several parameters reflecting diuretic effects in subjects with type 2 diabetes who were treated with SGLT2 inhibitors. A total of 70 subjects (male: n=45, age: 53.5±10.1 SD years, BMI: 29.3±4.5 kg/m2, HbA1c: 8.8±1.2%) with type 2 diabetes who were newly administered SGLT2 inhibitors from June 2014 to March 2017 were retrospectively identified from our database. Changes in HbA1c, hematocrit, urine specific gravity, uric acid, serum creatinine and plasma osmolarity levels between before and 30, 60, 90 and 120 days after the administration of the drugs were evaluated. Plasma osmolarity was calculated by the formula (2 x (Na[mEq/l] + K[mEq/l])) + (BUN[mg/dl] / 2.8) + (glucose[mg/dl] / 18). HbA1c was significantly decreased (30d: -0.57±0.53%; p=0.0vs. basal value, 60d: -0.88±1.04; p=0.002, 90d: -0.65±1.10; p&lt;0.001, 120d: -0.79±1.22; p&lt;0.001). Hematocrit was increased immediately after and remained high over 120 days (1.3±2.1%; p=0.05, 1.5±3.0; p=0.44, 2.5±2.8; p=0.002, 2.1±2.6; p=0.005). Urine specific gravity was also increased (0.007±0.01g/ml; p&lt;0.001, 0.003±0.010; p=0.02, 0.004±0.009; p=0.03, 0.007±0.011; p&lt;0.001). However, uric acid (30d: -0.10±0.80mg/dl; p=0.70), serum creatinine (0.04±0.07mg/dl; p=0.32) and plasma osmolarity (0.87±4.34mOsm/l; p=0.31) did not show change. No correlations were observed between changes in hematocrit and serum creatinine, uric acid or plasma osmolarity.
In conclusion, our data indicate that the elevation of hematocrit after the administration of SGLT2 inhibitors is unlikely to be caused by hemo-concentration via diuretic effect.

Disclosure
Y. Wada: None. Y. Hamamoto: None. Y. Iwasaki: None. Y. Nakatani: None. J. Fujikawa: None. S. Honjo: None. M. Aizawa-Abe: None. A. Hamasaki: None.