***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: Thiazolidinediones ( TZDs ) reduce urinary albumin excretion and proteinuria in diabetic nephropathy . The effect of TZDs on hard renal outcome in diabetic patients with chronic kidney disease ( CKD ) is unknown . We investigate the association of TZDs and risk of long-term dialysis or death in diabetic patients with advanced CKD . The nationwide population -based cohort study was conducted using Taiwan ’s National Health Insurance Research Data base . From January 2000 to June 2009 , 12350 diabetic patients with advanced CKD ( serum creatinine levels greater than 6 mg/dL but not yet receiving renal replacement therapy ) were selected for the study . We used multivariable Cox regression models and a propensity score-based matching technique to estimate hazard ratios ( HRs ) for development of long-term dialysis and the composite outcome of long-term dialysis or death for TZD users ( n=1224 ) as compared to nonusers ( n=11126 ) . During a median follow-up of 6 months , 8270 ( 67.0 % ) patients required long-term dialysis and 2593 ( 21.0 % ) patients died before starting long-term dialysis . Using propensity score matched analysis , we found TZD users were associated with a lower risk for long-term dialysis ( HR , 0.80 ; 95 % confidence interval [ CI ] , 0.74 - 0.86 ) and the composite outcome of long-term dialysis or death ( HR , 0.85 ; 95 % CI , 0.80 - 0.91 ) . The results were consistent across most patient subgroups . Use of TZDs among diabetic patients with advanced CKD was associated with lower risk for progression to end-stage renal disease necessitating long-term dialysis or death . Further r and omized controlled studies are required to vali date this association BACKGROUND The cardiovascular safety and efficacy of many current antihyperglycemic agents , including saxagliptin , a dipeptidyl peptidase 4 ( DPP-4 ) inhibitor , are unclear . METHODS We r and omly assigned 16,492 patients with type 2 diabetes who had a history of , or were at risk for , cardiovascular events to receive saxagliptin or placebo and followed them for a median of 2.1 years . Physicians were permitted to adjust other medications , including antihyperglycemic agents . The primary end point was a composite of cardiovascular death , myocardial infa rct ion , or ischemic stroke . RESULTS A primary end-point event occurred in 613 patients in the saxagliptin group and in 609 patients in the placebo group ( 7.3 % and 7.2 % , respectively , according to 2-year Kaplan-Meier estimates ; hazard ratio with saxagliptin , 1.00 ; 95 % confidence interval [ CI ] , 0.89 to 1.12 ; P=0.99 for superiority ; P<0.001 for noninferiority ) ; the results were similar in the " on-treatment " analysis ( hazard ratio , 1.03 ; 95 % CI , 0.91 to 1.17 ) . The major secondary end point of a composite of cardiovascular death , myocardial infa rct ion , stroke , hospitalization for unstable angina , coronary revascularization , or heart failure occurred in 1059 patients in the saxagliptin group and in 1034 patients in the placebo group ( 12.8 % and 12.4 % , respectively , according to 2-year Kaplan-Meier estimates ; hazard ratio , 1.02 ; 95 % CI , 0.94 to 1.11 ; P=0.66 ) . More patients in the saxagliptin group than in the placebo group were hospitalized for heart failure ( 3.5 % vs. 2.8 % ; hazard ratio , 1.27 ; 95 % CI , 1.07 to 1.51 ; P=0.007 ) . Rates of adjudicated cases of acute and chronic pancreatitis were similar in the two groups ( acute pancreatitis , 0.3 % in the saxagliptin group and 0.2 % in the placebo group ; chronic pancreatitis , < 0.1 % and 0.1 % in the two groups , respectively ) . CONCLUSIONS DPP-4 inhibition with saxagliptin did not increase or decrease the rate of ischemic events , though the rate of hospitalization for heart failure was increased . Although saxagliptin improves glycemic control , other approaches are necessary to reduce cardiovascular risk in patients with diabetes . ( Funded by AstraZeneca and Bristol-Myers Squibb ; SAVOR-TIMI 53 Clinical Trials.gov number , NCT01107886 . ) AIM To evaluate the efficacy and safety of saxagliptin vs. placebo in patients with type 2 diabetes mellitus ( T2DM ) and renal impairment . METHODS In this multicentre , r and omized , parallel-group , double-blind , placebo-controlled study , patients with glycated haemoglobin ( HbA1c ) 7 - 11 % and creatinine clearance < 50 ml/min were stratified by baseline renal impairment ( moderate , severe or end-stage on haemodialysis ) , and r and omized ( 1 : 1 ) to saxagliptin 2.5 mg once daily or placebo for 12 weeks . Oral antihyperglycaemic drugs and insulin therapy present at enrolment were continued throughout the study . The absolute change in HbA1c from baseline to week 12 ( primary efficacy end-point ) was analysed using an analysis of covariance model with last observation carried forward methodology . RESULTS A total of 170 patients were r and omized and treated . The adjusted mean decrease from baseline to week 12 in HbA1c was statistically significantly greater in the saxagliptin group than in the placebo group ; the difference between treatments was -0.42 % ( 95 % confidence interval : -0.71 to -0.12 % , p = 0.007 ) . Adjusted mean HbA1c decreases from baseline to week 12 were numerically greater with saxagliptin than with placebo in the subgroups of patients with moderate ( -0.64 vs. -0.05 % ) and severe ( -0.95 vs. -0.50 % ) renal impairment . HbA1c reductions were similar between saxagliptin and placebo in the subgroup with end-stage renal disease on haemodialysis ( -0.84 vs. -0.87 % ) . Saxagliptin was generally well tolerated ; incidences of adverse events and hypoglycaemic events were similar to placebo . CONCLUSIONS Saxagliptin 2.5 mg once daily is a well-tolerated treatment option for patients with inadequately controlled T2DM and renal impairment BACKGROUND Treatment with oral antihyperglycemic agents has not been well characterized in patients with type 2 diabetes and end-stage renal disease ( ESRD ) . The efficacy and safety of sitagliptin and glipizide monotherapy in patients with type 2 diabetes and ESRD on dialysis therapy were assessed in this study . STUDY DESIGN 54-week , r and omized , double-blind , parallel-arm study . SETTING & PARTICIPANTS From 31 clinical sites in 12 countries , 129 patients 30 years or older with type 2 diabetes and ESRD who were on dialysis therapy and had a hemoglobin A1c ( HbA1c ) level of 7%-9 % were r and omly assigned 1:1 to treatment . INTERVENTION Monotherapy with sitagliptin , 25 mg daily or glipizide ( initiated with 2.5 mg daily and titrated up to a potential maximum dose of 10 mg twice daily or down to avoid hypoglycemia ) . OUTCOMES Primary end points were 54-week change in HbA1c level from baseline and tolerability with sitagliptin .  A secondary end point was the comparison of sitagliptin versus glipizide on the incidence of symptomatic hypoglycemia . RESULTS Of 129 patients r and omly assigned , 64 were in the sitagliptin group ( mean baseline age , 61 years ; HbA1c , 7.9 % ) and 65 were in the glipizide group ( mean baseline age , 59 years ; HbA1c , 7.8 % ) . After 54 weeks , the least squares mean change from baseline in HbA1c level was -0.72 % ( 95 % CI , -0.95 % to -0.48 % ) with sitagliptin and -0.87 % ( 95 % CI , -1.11 % to -0.63 % ) with glipizide , for a difference of 0.15 % ( 95 % CI , -0.18 % to 0.49 % ) . The incidences of symptomatic hypoglycemia and severe hypoglycemia were 6.3 % versus 10.8 % ( between-group difference , -4.8 % [ 95 % CI , -15.7 % to 5.6 % ] ) and 0 % versus 7.7 % ( between-group difference , -7.8 % [ 95 % CI , -17.1 % to -1.9 % ] ) in the sitagliptin and glipizide groups , respectively . Higher incidences ( ie , 95 % CI around between-treatment difference excluded 0 ) of cellulitis and headache were found with sitagliptin compared to glipizide ( 6.3 % vs 0 % , respectively , for both ) . LIMITATIONS Small sample size limits between-group comparisons . CONCLUSIONS Treatment with sitagliptin or glipizide monotherapy was effective and well tolerated over 54 weeks in patients with type 2 diabetes and ESRD who were receiving dialysis OBJECTIVE Patients with type 2 diabetes mellitus ( T2DM ) and chronic kidney disease have an increased risk of micro- and macrovascular disease , but limited options for antihyperglycemic therapy . We compared the efficacy and safety of sitagliptin with glipizide in patients with T2DM and moderate-to-severe chronic renal insufficiency and inadequate glycemic control . RESEARCH DESIGN AND METHODS Patients ( n = 426 ) were r and omized 1:1 to sitagliptin ( 50 mg every day [ q.d . ] for moderate renal insufficiency and 25 mg q.d . for severe renal insufficiency ) or glipizide ( 2.5 mg q.d . , adjusted based on glycemic control to a 10-mg twice a day maximum dose ) . R and omization was stratified by : 1 ) renal status ( moderate or severe renal insufficiency ) ; 2 ) history of cardiovascular disease ; and 3 ) history of heart failure . RESULTS At week 54 , treatment with sitagliptin was noninferior to treatment with glipizide in A1C change from baseline ( −0.8 vs. −0.6 % ; between-group difference −0.11 % ; 95 % CI −0.29 to 0.06 ) because the upper bound of the 95 % CI was less than the prespecified noninferiority margin of 0.4 % . There was a lower incidence of symptomatic hypoglycemia adverse events ( AEs ) with sitagliptin versus glipizide ( 6.2 and 17.0 % , respectively ; P = 0.001 ) and a decrease in body weight  with sitagliptin ( −0.6 kg ) versus an increase ( 1.2 kg ) with glipizide ( difference , −1.8 kg ; P < 0.001 ) . The incidence of gastrointestinal AEs was low with both treatments . CONCLUSIONS In patients with T2DM and chronic renal insufficiency , sitagliptin and glipizide provided similar A1C-lowering efficacy . Sitagliptin was generally well-tolerated , with a lower risk of hypoglycemia and weight loss versus weight gain , relative to glipizide OBJECTIVE To assess the safety of sitagliptin in patients with type 2 diabetes and moderate [ creatinine clearance ( CrCl ) > or = 30 to < 50 ml/min ] or severe renal insufficiency [ CrCl < 30 ml/min including patients with end-stage renal disease ( ESRD ) on dialysis ] . The efficacy of sitagliptin in this patient population was also assessed . METHODS In a 54-week , r and omized , double-blind , parallel-group study , patients with baseline glycosylated haemoglobin A(1c ) ( HbA(1c ) ) values of 6.5 - 10 % were allocated ( 2:1 ) to sitagliptin ( for 54 weeks ) or the sequence of placebo ( for 12 weeks ) followed by active treatment with glipizide ( for 42 weeks ) . To achieve plasma concentrations similar to those observed in patients with normal renal function treated with 100 mg sitagliptin once daily , patients with moderate renal insufficiency were allocated to receive sitagliptin 50 mg once daily and patients with severe renal insufficiency to receive 25 mg once daily . Glipizide treatment was initiated at 2.5 
    Output:
    
DISCUSSION DPP-4 inhibitors demonstrated beneficial effects on the glycemic control for diabetic patients with CKD without causing any additional adverse effects .