***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: PURPOSE To evaluate the influence of renal function on the efficacy and safety of the sodium glucose cotransporter 2 inhibitor luseogliflozin ( TS-071 ) in Japanese patients with type 2 diabetes mellitus ( T2DM ) . METHODS Study 1 was a 52-week , Phase III study to evaluate the efficacy and safety of 2.5 mg/d luseogliflozin ( or increased to 5 mg/d ) in patients with T2DM with moderate renal impairment . During the initial 24 weeks , efficacy and safety of luseogliflozin were compared with placebo . Study 2 was a pooled analysis of four 52-week , Phase III studies of luseogliflozin , including Study 1 , to evaluate the efficacy and safety of luseogliflozin in patients with various degrees of renal function . Patients were stratified into 3 groups by baseline estimated glomerular filtration rate ( eGFR ) : normal renal function ( ≥90 mL/min/1.73 m(2 ) ) , mild impairment ( ≥60 to < 90 mL/min/1.73 m(2 ) ) , and moderate impairment ( ≥30 to < 60 mL/min/1.73 m(2 ) ) . Patients with moderate impairment were further divided into those with mild-moderate ( ≥45 to < 60 mL/min/1.73 m(2 ) ) and moderate-severe ( ≥30 to < 45 mL/min/1.73 m(2 ) ) . In both studies , efficacy end points included changes in glycated hemoglobin ( HbA1c ) level , fasting plasma glucose ( FPG ) level , and body weight . The safety end points included adverse events ( AEs ) and laboratory parameters . FINDINGS In Study 1 , HbA1c , FPG , and body weight significantly decreased at Week 24 in patients treated with luseogliflozin compared with patients treated with placebo , with the decrease in these parameters also observed with luseogliflozin at Week 52 . The incidence of AEs was similar between groups . In Study 2 , 1030 patients were included ( normal , 275 ; mildly impaired , 598 ; and moderately impaired , 157 ) . At Week 52 , HbA1c , FPG , and body weight were significantly decreased from baseline in all groups . In between-group comparisons , the decreases in HbA1c and body weight were significantly smaller in patients with moderate impairment than in those with normal function ; however , the HbA1c-lowering efficacy was reduced by nearly half , whereas the efficacy of body weight lowering was not so much diminished in the moderate impairment group . Furthermore , a scatter plot showed that changes in HbA1c were more influenced by baseline HbA1c than by baseline eGFR . The incidence of AEs during 52 weeks was similar among all groups , with the majority being mild . IMPLICATION S Luseogliflozin  improved glycemic control and reduced body weight in all eGFR groups , and its efficacy on HbA1c lowering was reduced in those with moderate renal impairment . Luseogliflozin was well tolerated and safe , with no significant safety issues identified , regardless of baseline eGFR . The study is registered with Clinical Trials Information/JapicCTI of the Japan Pharmaceutical Information Center , and the study registry identification numbers are JapicCTI-111507 , JapicCTI-111508 , JapicCTI-111509 , and JapicCTI-111543 PURPOSE The goal of this study was to investigate the pharmacodynamic effects of co-administration of empagliflozin , a sodium glucose cotransporter 2 inhibitor , with diuretic agents . METHODS In a r and omized , open-label cross-over study , 22 patients with type 2 diabetes mellitus received empagliflozin 25 mg for 5 days and either hydrochlorothiazide 25 mg for 4 days followed by hydrochlorothiazide 25 mg plus empagliflozin 25 mg for 5 days , or torasemide 5 mg for 4 days followed by torasemide 5 mg plus empagliflozin 25 mg for 5 days ; 20 completed treatment . Food , fluid , and sodium intake were st and ardized for 3 days before and during treatment . FINDINGS At baseline , the median age of the treated patients was 56 years ( range , 40 - 65 years ) , body mass index was 26.8 kg/m2 ( range , 20.1 - 34.4 kg/m2 ) , fasting plasma glucose was 8.6 mmol/L ( range , 6.0 - 12.9 mmol/L ) , and glycosylated hemoglobin level was 7.6 % ( range , 7%-10 % ) . Empagliflozin significantly increased 24-hour urinary glucose excretion and reduced fasting serum glucose levels . These effects were maintained after co-administration with either diuretic . Urinary sodium excretion did not significantly change with empagliflozin or diuretic administration alone , but seemed to increase compared with either diuretic alone when empagliflozin was co-administered with either diuretic . Plasma renin and serum aldosterone levels were unaltered with empagliflozin or torasemide alone , but tended to increase with hydrochlorothiazide alone , and tended to increase when empagliflozin was co-administered with a diuretic compared with either diuretic alone . Urinary volume did not increase with empagliflozin or diuretics alone , but increased when empagliflozin was co-administered with either diuretic . IMPLICATION S Empagliflozin alone for 5 days increased urinary glucose excretion but did not seem to have a relevant impact on urine volume or electrolytes . When empagliflozin was co-administered with a diuretic agent , urinary glucose excretion remained increased , and the renin-angiotensin system was activated . Clinical trials.gov identifier : NCT01276288 OBJECTIVE To investigate the efficacy , safety , and tolerability of empagliflozin in patients with type 2 diabetes and hypertension . RESEARCH DESIGN AND METHODS Patients ( N = 825 ) with type 2 diabetes and hypertension ( mean seated systolic blood pressure [ SBP ] 130–159 mmHg and diastolic blood pressure [ DBP ] 80–99 mmHg ) were r and omized ( double blind ) to 10 mg or 25 mg empagliflozin or placebo once daily for 12 weeks . RESULTS At week 12 , adjusted mean difference versus placebo in change from baseline in mean 24-h SBP ( ambulatory blood pressure monitoring [ ABPM ] ) was −3.44 mmHg ( 95 % CI −4.78 , −2.09 ) with 10 mg empagliflozin and −4.16 mmHg ( −5.50 , −2.83 ) with 25 mg empagliflozin ( both P < 0.001 ) . At week 12 , adjusted mean difference versus placebo in change from baseline in mean 24-h DBP ( ABPM ) was −1.36 mmHg ( 95 % CI −2.15 , −0.56 ) with 10 mg empagliflozin and −1.72 mmHg ( 95 % CI −2.51 , −0.93 ) with 25 mg empagliflozin ( both P < 0.001 ) . Changes in office BP were consistent with ABPM . Adjusted mean difference versus placebo in change from baseline in HbA1c at week 12 was −0.62 % ( 95 % CI −0.72 , −0.52 ) ( −6.8 mmol/mol [ 95 % CI −7.9 , −5.7 ] ) with 10 mg empagliflozin and −0.65 % ( 95 % CI −0.75 , −0.55 ) ( −7.1 mmol/mol [ 95 % CI −8.2 , −6.0 ] ) with 25 mg empagliflozin ( both P < 0.001 )  . Empagliflozin was well tolerated . One patient on placebo and one patient on 10 mg empagliflozin reported events consistent with volume depletion . CONCLUSIONS Empagliflozin was associated with significant and clinical ly meaningful reductions in BP and HbA1c versus placebo and was well tolerated in patients with type 2 diabetes and hypertension Background This study evaluated the effect of empagliflozin on postpr and ial glucose ( PPG ) and 24-hour glucose variability in Japanese patients with type 2 diabetes mellitus ( T2DM ) . Methods Patients ( N = 60 ; baseline mean [ SD ] HbA1c 7.91 [0.80]% ; body mass index 24.3 [ 3.2 ] kg/m2 ) were r and omized to receive empagliflozin 10 mg ( n = 20 ) , empagliflozin 25 mg ( n = 19 ) or placebo ( n = 21 ) once daily as monotherapy for 28 days . A meal tolerance test and continuous glucose monitoring ( CGM ) for 24 hours were performed at baseline and on days 1 and 28 . The primary endpoint was change from baseline in area under the glucose concentration-time curve 3 hours after breakfast ( AUC1–4h for PPG ) at day 28 . Results Adjusted mean ( 95 % ) differences versus placebo in changes from baseline in AUC1 - 4h for PPG at day 1 were −97.1 ( −126.5 , −67.8 ) mg · h/dl with empagliflozin 10 mg and −91.6 ( −120.4 , −62.8 ) mg · h/dl with empagliflozin 25 mg ( both p < 0.001 versus placebo ) and at day 28 were −85.5 ( −126.0 , −45.0 ) mg · h/dl with empagliflozin 10 mg and −104.9 ( −144.8 , −65.0 ) mg · h/dl with empagliflozin 25 mg ( both p < 0.001 versus placebo ) . Adjusted mean ( 95 % CI ) differences versus placebo in change from baseline in 24-hour mean glucose ( CGM ) at day 1 were −20.8 ( −27.0 , −14.7 ) mg/dl with empagliflozin 10 mg and −23.9 ( −30.0 , −17.9 ) mg/dl with empagliflozin 25 mg ( both p < 0.001 versus placebo ) and at day 28 were −24.5 ( −35.4 , −13.6 ) mg/dl with empagliflozin 10 mg and −31.7 ( −42.5,-20.9 ) mg/dl with empagliflozin 25 mg ( both p < 0.001 versus placebo ) . Changes from baseline in mean amplitude of glucose excursions ( MAGE ; CGM ) were not significantly different with either empagliflozin dose versus placebo at either timepoint . Curves of mean glucose ( CGM ) did not change between baseline and day 1 or 28 with placebo , but shifted downward with empagliflozin . Percentage of time with glucose ≥70 to < 180 mg/dl increased from 52.0 % at baseline to 77.0 % at day 28 with empagliflozin 10 mg and from 55.0 % to 81.1 % with empagliflozin 25 mg , without increasing time spent with hypoglycemia . Conclusion Empagliflozin for 28 days reduced PPG from the first day and improved daily blood glucose control in Japanese patients with T2DM.Trial registration Clinical trials.gov Background — The primary objective of this mechanistic open-label , stratified clinical trial was to determine the effect of 8 weeks ’ sodium glucose cotransporter 2 inhibition with empagliflozin 25 mg QD on renal hyperfiltration in subjects with type 1 diabetes mellitus ( T1D ) . Methods and Results — Inulin ( glomerular filtration rate ; GFR ) and paraaminohippurate ( effective renal plasma flow ) clearances were measured in individuals stratified based on having hyperfiltration ( T1D-H , GFR ≥ 135 mL/min/1.73m2 , n=27 ) or normal GFR ( T1D-N , GFR 90–134 mL/min/1.73m2 , n=13 ) at baseline . Renal function and circulating levels of renin-angiotensin-aldosterone system mediators and NO were measured under clamped euglycemic ( 4–6 mmol/L ) and hyperglycemic ( 9–11 mmol/L ) conditions at baseline and end of treatment . During clamped euglycemia , hyperfiltration was at 
    Output:
    
There was no evidence of additional risks with SGLT2 inhibition in CKD beyond those already known for the class , although heterogeneity was observed across individual agents for some safety outcomes .
Currently available data suggest that , despite only modest reductions in glycated haemoglobin , SGLT2 inhibitors reduce the risk of cardiovascular and renal outcomes in patients with T2DM and CKD , without clear evidence of additional safety concerns