***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: OBJECTIVE To investigate the efficacy and tolerability of empagliflozin as add-on to metformin and sulfonylurea in patients with type 2 diabetes . RESEARCH DESIGN AND METHODS Patients inadequately controlled on metformin and sulfonylurea ( HbA1c ≥7 to ≤10 % ) were r and omized and treated with once-daily empagliflozin 10 mg ( n = 225 ) , empagliflozin 25 mg ( n = 216 ) , or placebo ( n = 225 ) for 24 weeks . The primary end point was change from baseline in HbA1c at week 24 . Key secondary end points were changes from baseline in weight and mean daily glucose ( MDG ) at week 24 . RESULTS At week 24 , adjusted mean ( SE ) changes from baseline in HbA1c were −0.17 % ( 0.05 ) for placebo vs. −0.82 % ( 0.05 ) and −0.77 % ( 0.05 ) for empagliflozin 10 and 25 mg , respectively ( both P < 0.001 ) . Empagliflozin significantly reduced MDG , weight , and systolic ( but not diastolic ) blood pressure versus placebo . Adverse events were reported in 62.7 , 67.9 , and 64.1 % of patients on placebo and empagliflozin 10 and 25 mg , respectively . Events consistent with urinary tract infection were reported in 8.0 , 10.3 , and 8.3 % of patients on placebo and empagliflozin 10 and 25 mg , respectively ( females : 13.3 , 18.0 , and 17.5 % , respectively ; males : 2.7 , 2.7 , and 0 % , respectively ) . Events consistent with genital infection were reported in 0.9 , 2.7 , and 2.3 % of patients on placebo and empagliflozin 10 and 25 mg , respectively ( females : 0.9 , 4.5 , and 3.9 % , respectively ; males : 0.9 % in each group ) . CONCLUSIONS Empagliflozin 10 and 25 mg for 24 weeks as add-on to metformin plus sulfonylurea improved glycemic control , weight , and systolic blood pressure and were well tolerated AIMS Dapagliflozin , a highly selective inhibitor of sodium-glucose cotransporter 2 ( SGLT2 ) , reduces hyperglycaemia and weight in patients with type 2 diabetes mellitus ( T2DM ) by increasing urinary glucose excretion . Long-term glycaemic control , body composition and bone safety were evaluated in patients with T2DM after 102 weeks of dapagliflozin treatment . METHODS This r and omized , double-blind , placebo-controlled study ( NCT00855166 ) enrolled patients with T2DM [ mean : age 60.7 years ; HbA1c 7.2 % ; body mass index ( BMI ) 31.9 kg/m(2 ) ; body weight 91.5 kg ] inadequately controlled on metformin . Patients ( N = 182 ) were r and omly assigned 1 : 1 to receive dapagliflozin 10 mg/day or placebo added to open-label metformin for a 24-week double-blind treatment period followed by a 78-week site- and patient-blinded extension period . At week 102 , changes from baseline in HbA1c , weight , waist circumference , total body fat mass as measured by dual-energy X-ray absorptiometry ( DXA ) , serum markers of bone turnover , bone mineral density ( BMD ) as measured by DXA , and adverse events were evaluated . RESULTS A total of 140 patients ( 76.9 % ) completed the study . Over 102 weeks , dapagliflozin-treated patients showed reductions in HbA1c by -0.3 % , weight by -4.54 kg , waist circumference by -5.0 cm and fat mass by -2.80 kg without increase in rate of hypoglycaemia . Compared with placebo , no meaningful changes from baseline in markers of bone turnover or BMD were identified over 102 weeks . One fracture occurred in each treatment group . The frequency of urinary tract infection ( UTI ) and genital infection was similar in both treatment groups . CONCLUSIONS Over 102 weeks , dapagliflozin improved glycaemic control , and reduced weight and fat mass , without affecting markers of bone turnover or BMD in patients with T2DM inadequately controlled on metformin ABSTRACT Review of : Neal B , Perkovic V , Mahaffey K , et al. Canagliflozin and cardiovascular and renal events in type 2 diabetes . N Engl J Med . 2017;377:644–657 . The report combines the data from two trials , CANVAS and CANVAS-Renal , which were design ed to evaluate the safety and effect of canagliflozin , an SGLT-2 inhibitor , on the appearance of cardiovascular and renal events in patients with type 2 diabetes . Enrollees were patients with type 2 diabetes of at least 30 years of age , with a glycated hemoglobin of > or equal to 7.0 % and < or equal to 10.5 % . Patients either had to have preexisting cardiovascular disease or to be at elevated risk for cardiovascular disease , and to have an estimated glomerular filtration rate ( eGFR ) of > 30 ml/min . Patients were r and omized to canagliflozin at doses of either 100 mg or 300 mg or matching placebo in CANVAS , and to canagliflozin 100 mg with a possible increase to 300 mg , or placebo , in CANVAS-Renal . Physicians were instructed to continue appropriate diabetic management and other therapies in accordance with the best practice s in their community . There was a significant 14 % reduction in the combined endpoint of cardiovascular events of death from cardiovascular causes , nonfatal myocardial infa rct ion , or nonfatal stroke in the canagliflozin treated patients . There was also a pattern of improvement in markers of renal disease , including the change in the level and nature of albuminuria , a 40 % decrease in the glomerular filtration rate , the need for renal replacement therapy , or death from renal causes . This study exp and s the scope of SGLT-2 inhibitor therapy to prevent cardiovascular disease in diabetic patients beyond those with preexisting cardiovascular disease studied in the previous empagliflozin study , raising the question as to whether SGLT-2 inhibitor therapy should be considered appropriate for most , if not all , type 2 diabetes patients , not only to control hyperglycemia but also to reduce cardiovascular and renal events The mechanisms by which SGLT‐2 inhibitors lower albuminuria are incompletely understood . We assessed in a post‐hoc analysis of a cross‐over trial the effects of the SGLT2 inhibitor dapagliflozin on glomerular markers ( IgG to IgG4 and IgG to albumin ) , tubular markers ( urinary KIM‐1 , NGAL and LFABP ) and inflammatory markers ( urinary MCP‐1 and IL‐6 ) to provide more insight into kidney protective effects . Dapagliflozin  decreased albuminuria by 43.9 % ( 95 % CI , 30.3%‐54.8 % ) and eGFR by 5.1 ( 2.0‐8.1 ) mL/min/1.73m2 compared to placebo . Dapagliflozin did not change glomerular charge or size selectivity index compared to placebo . Dapagliflozin  decreased urinary KIM‐1 excretion by 22.6 % ( 0.3%‐39.8 % ; P = .05 ) and IL‐6 excretion by 23.5 % ( 1.4%‐40.6 % ; P = .04 ) compared to placebo , whereas no changes in NGAL , LFABP and MCP‐1 were observed . During dapagliflozin treatment , changes in albuminuria correlated with changes in eGFR ( r = 0.36 ; P = .05 ) and KIM‐1 ( r = 0.39 ; P = .05 ) . In conclusion , the albuminuria‐lowering effect of 6 weeks of dapagliflozin therapy may be the result of decreased intraglomerular pressure or reduced tubular cell injury Aims To investigate the efficacy and tolerability of empagliflozin added to basal insulin‐treated type 2 diabetes . Methods Patients inadequately controlled [ glycated haemoglobin ( HbA1c ) > 7 to ≤10 % ( > 53 to ≤86 mmol/mol ) ] on basal insulin ( glargine , detemir , NPH ) were r and omized to empagliflozin 10 mg ( n = 169 ) , empagliflozin 25 mg ( n = 155 ) or placebo ( n = 170 ) for 78 weeks . The baseline characteristics were balanced among the groups [ mean HbA1c 8.2 % ( 67 mmol/mol ) , BMI 32.2 kg/m2 ] . The basal insulin dose was to remain constant for 18 weeks , then could be adjusted at investigator 's discretion . The primary endpoint was change from baseline in HbA1c at week 18 . Key secondary endpoints were changes from baseline in HbA1c and insulin dose at week 78 . Results At week 18 , the adjusted mean ± st and ard error changes from baseline in HbA1c were 0.0 ± 0.1 % ( −0.1 ± 0.8 mmol/mol ) for placebo , compared with −0.6 ± 0.1 % ( −6.2 ± 0.8 mmol/mol ) and −0.7 ± 0.1 % ( −7.8 ± 0.8 mmol/mol ) for empagliflozin 10 and 25 mg , respectively ( both p < 0.001 ) . At week 78 , empagliflozin 10 and 25 mg significantly reduced HbA1c , insulin dose and weight vs placebo ( all  p < 0.01 ) , and empagliflozin 10 mg significantly reduced systolic blood pressure vs placebo ( p = 0.004 ) . Similar percentages of patients had confirmed hypoglycaemia in all groups ( 35–36 % ) . Events consistent with urinary tract infection were reported in 9 , 15 and 12 % of patients on  placebo , empagliflozin 10 and 25 mg , and events consistent with genital infection were reported in 2 , 8 and 5 % , respectively .  Conclusions Empagliflozin for 78 weeks added to basal insulin improved glycaemic control and reduced weight with a similar risk of hypoglycaemia to placebo BACKGROUND Diabetes is a leading cause of chronic kidney disease ( CKD ) worldwide . Optimum glycaemic control in patients with type 2 diabetes is important to minimise the risk of microvascular and macrovascular complications and to slow the progression of CKD . We assessed the efficacy and safety of empagliflozin as an add-on treatment in patients with type 2 diabetes and CKD . METHODS We did a phase 3 , r and omised , double-blind , parallel-group , placebo-controlled trial at 127 centres in 15 countries . Patients with HbA1c of 7 % or greater to 10 % or less were eligible for inclusion . Patients with stage 2 CKD ( estimated glomerular filtration rate [ eGFR ] ≥60 to < 90 mL/min per 1·73 m(2 ) ; n=290 ) were r and omly assigned ( 1:1:1 ) to receive empagliflozin 10 mg or 25 mg or placebo once daily for 52 weeks . Patients with stage 3 CKD ( eGFR ≥30 to < 60 mL/min per 1·73 m(2 ) ; n=374 ) were r and omly assigned ( 1:1 ) to receive empagliflozin 25 mg or placebo for 52 weeks . R and omisation was done with a computer-generated r and om sequence and stratified by renal impairment , HbA1c , and background antidiabetes medication . Treatment assignment was masked from patients and investigators . The primary endpoint was change from baseline in HbA1c at week 24 by ANCOVA in the full analysis set . This study is registered with Clinical Trials.gov , number NCT01164501 . FINDINGS In patients with stage 2 CKD , adjusted mean treatment differences versus placebo in changes from baseline in HbA1c at week 24 were -0·52 % ( 95 % CI -0·72 to -0·32 ) for empagliflozin 10 mg and -0·68 % ( -0·88 to -0·49 ) for empagliflozin 25 mg ( both p<0·0001 ) . In patients with stage 3 
    Output:
    
SGLT2is slowed eGFR decline , lowered albuminuria progression , improved adverse renal endpoints and reduced all-cause mortality , but increased risk of genital infections vs placebo in patients with T2DM .
The indication of consistent renal benefits across categories of baseline eGFR levels may allow additional individuals to benefit from SGLT2is therapy