***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 Background Evidence concerning the importance of glucose lowering in the prevention of cardiovascular ( CV ) outcomes remains controversial . Given the multi-faceted pathogenesis of atherosclerosis in diabetes , it is likely that any intervention to mitigate this risk must address CV risk factors beyond glycemia alone . The SGLT-2 inhibitor empagliflozin improves glucose control , body weight and blood pressure when used as monotherapy or add-on to other antihyperglycemic agents in patients with type 2 diabetes . The aim of the ongoing EMPA-REG OUTCOME ™ trial is to determine the long-term CV safety of empagliflozin , as well as investigating potential benefits on macro-/microvascular outcomes . Methods Patients who were drug-naïve ( HbA1c ≥7.0 % and ≤9.0 % ) , or on background glucose-lowering therapy ( HbA1c ≥7.0 % and ≤10.0 % ) , and were at high risk of CV events , were r and omized ( 1:1:1 ) and treated with empagliflozin 10 mg , empagliflozin 25 mg , or placebo ( double blind , double dummy ) superimposed upon the st and ard of care . The primary outcome is time to first occurrence of CV death , non-fatal myocardial infa rct ion , or non-fatal stroke . CV events will be prospect ively adjudicated by an independent Clinical Events Committee . The trial will continue until ≥691 confirmed primary outcome events have occurred , providing a power of 90 % to yield an upper limit of the adjusted 95 % CI for a hazard ratio of < 1.3 with a one-sided α of 0.025 , assuming equal risks between placebo and empagliflozin ( both doses pooled ) . Hierarchical testing for superiority will follow for the primary outcome and key secondary outcomes ( time to first occurrence of CV death , non-fatal myocardial infa rct ion , non-fatal stroke or hospitalization for unstable angina pectoris ) where non-inferiority is achieved . Results Between Sept 2010 and April 2013 , 592 clinical sites r and omized and treated 7034 patients ( 41 % from Europe , 20 % from North America , and 19 % from Asia ) . At baseline , the mean age was 63 ± 9 years , BMI 30.6 ± 5.3 kg/m2 , HbA1c 8.1 ± 0.8 % , and eGFR 74 ± 21 ml/min/1.73 m2 . The study is expected to report in 2015 . Discussion EMPA-REG OUTCOME ™ will determine the CV safety of empagliflozin in a cohort of patients with type 2 diabetes and high CV risk , with the potential to show cardioprotection . Trial registration Clinical trials.gov Aims We examined the efficacy , safety and tolerability of canagliflozin , a sodium glucose co-transporter 2 inhibitor , in Japanese patients with type 2 diabetes ( T2DM ) undergoing diet and exercise therapy . Methods Patients aged 20–80 years with T2DM diagnosed ≥3 months previously , and HbA1c of 6.9–9.9 % were r and omized to 50 , 100 , 200 or 300 mg canagliflozin or placebo once daily for 12 weeks . The primary and secondary endpoints were changes in HbA1c , fasting plasma glucose ( FPG ) , urinary glucose/creatinine and postpr and ial glycaemic parameters following a meal test . The safety assessment s included adverse events ( AEs ) and clinical laboratory tests . Results Overall , 383 patients were r and omized to receive either placebo ( n = 75 ) , or 50 mg ( n = 82 ) , 100 mg ( n = 74 ) , 200 mg ( n = 77 ) or 300 mg canagliflozin ( n = 75 ) . At week 12 , significant reductions in HbA1c were observed in all canagliflozin groups relative to placebo ( −0.61 , –0.80 , –0.79 and −0.88 % for 50 , 100 , 200 and 300 mg , respectively , versus + 0.11 % for placebo ; all , p < 0.01 ) . FPG and postpr and ial glycaemic parameters improved significantly in the canagliflozin  groups . Body weight was significantly decreased by canagliflozin . No deaths or drug-related serious AEs were reported . There was no dose-dependent increase in the incidence of AEs in the canagliflozin groups . The incidence of hypoglycaemia was low ; episodes were not severe or dose dependent . Canagliflozin did not affect serum creatinine levels or the urinary albumin/creatinine ratio . Conclusions Treatment with canagliflozin for 12 weeks significantly improved glycaemic control and reduced body weight in Japanese patients with T2DM . Canagliflozin was well tolerated Background As a first-line diabetes drug that is widely prescribed around the world , metformin has been demonstrated to be effective in reducing microvascular risk , in addition to lowering glucose levels . Specifically , metformin use has been shown to be associated with improved lipid profiles , such as increased levels of high-density lipoprotein cholesterol ( HDL-C ) . However , no study has been performed to examine the differential response in HDL-C levels to metformin treatment by race/ethnicity . Methods Here , based on a re- analysis of the data from the Diabetes Prevention Program , which involved pre-diabetic participants receiving 850 mg of metformin twice daily , we compared the lipid profile changes following the metformin use . The participants were composed of 602 Whites , 221 African Americans ( AAs ) and 162 Hispanics . Results We found that the one-year metformin treatment result ed in a significant increase in HDL-C levels in Whites ( p = 0.002 ) and AAs ( p = 0.016 ) , but not in Hispanics . Consistently , both Whites ( p = 0.018 ) and AAs ( p = 0.020 ) had more pronounced changes in HDL-C levels than Hispanics following metformin treatment . Conclusion This result suggests a notion that Whites and AAs are more responsive than Hispanics to one-year metformin use in HDL-C level changes , and that racial and ethnic identity is a factor to consider when interpreting the effects of metformin treatment on lipid profiles Introduction This study was design ed to determine the efficacy and tolerability of empagliflozin monotherapy in Japanese patients with type 2 diabetes mellitus ( T2DM ) . Methods Patients with glycosylated hemoglobin ( HbA1c ) ≥7.0–≤10 % were r and omized via an interactive web response system , and treated double-blind with empagliflozin 5 , 10 , 25 , 50 mg , or placebo once daily for 12 weeks . The primary endpoint was change from baseline in HbA1c at week 12 . Other endpoints included percentage of patients with HbA1c < 7.0 % and changes from baseline in fasting plasma glucose ( FPG ) , body weight , and systolic blood pressure ( SBP ) at week 12 . Results A total of 547 patients were r and omized and treated with empagliflozin 5 mg ( n = 110 ) , 10 mg ( n = 109 ) , 25 mg ( n = 109 ) , 50 mg ( n = 110 ) , or placebo ( n = 109 ) for 12 weeks . Adjusted mean [ 95 % confidence interval ( CI ) ] differences vs. placebo in changes from baseline in HbA1c were −0.72 % ( −0.87 , −0.57 ) with empagliflozin 5 mg , −0.70 % ( −0.85 , −0.55 ) with 10 mg , −0.95 % ( −1.10 , −0.80 ) with 25 mg , and −0.91 ( −1.06 , −0.76 ) with 50 mg ( all p < 0.001 ) . More patients with HbA1c ≥7.0 % at baseline reached HbA1c < 7.0 % with empagliflozin ( 19–33 % ) than placebo ( 3 % ) . Compared with placebo , empagliflozin reduced FPG , body weight ( p < 0.001 for all doses for both endpoints ) and SBP ( p = 0.001 , p = 0.014 and p = 0.003 for empagliflozin 10 , 25 , and 50 mg , respectively ) . Adverse events were reported by 42 % of patients receiving placebo and 33–38 % of patients receiving empagliflozin . There were few reports of confirmed hypoglycemic adverse events or events consistent with urinary tract infection or genital infection in any treatment group . Conclusions Empagliflozin monotherapy for 12 weeks in Japanese patients with T2DM reduced HbA1c , FPG , body weight and SBP , and was well tolerated SUMMARY Abstract Background Combination therapy with canagliflozin and insulin was investigated in a prescribed sub study of the canagliflozin Cardiovascular Assessment Study ( CANVAS ) ; however , it was not evaluated in Japanese patients with type 2 diabetes mellitus ( T2DM ) . Since the usage profile of insulin therapy and pathologic features of Japanese patients differ from those of Caucasian patients , we determined the clinical benefit of such a combination therapy in Japanese patients . Methods Patients who had inadequate glycemic control despite insulin , diet and exercise therapies were 
    Output:
    
SGLT2is significantly improved HbA1c [ mean difference - 0.80 ( 95%CI - 0.96 to - 0.64)% , p < 0.00001 ] , TG [ mean difference - 16.42 ( 95%CI - 22.71 to - 10.12 ) mg/dL , p < 0.00001 ] , and HDL-C [ mean difference 3.36 ( 95%CI 2.73 to 3.98 ) mg/dL , p < 0.00001 ] , but significantly deteriorated LDL-C [ mean difference 3.00 ( 95%CI 1.18 to 4.82 ) mg/dL , p < 0.001 ] .
Conclusion The present results suggest that in Asian patients with type 2 diabetes mellitus , TG and HDL-C values were better , while LDL-C values were worse with SGLT2is than with a placebo .
However , the negative impact of SGLT2is on lipid profiles was modest .
The present results will be informative for SGLT2is users with concerns regarding the effects of SGLT2is on lipid profiles