***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 
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    ***EXAMPLES*** 
    Input: Background In a previous pooled analysis of 12 double-blind clinical studies that included data on 6,139 patients with type 2 diabetes , treatment with sitagliptin  , a dipeptidyl peptidase-4 ( DPP-4 ) inhibitor , was shown to be generally well tolerated compared with treatment with control agents . As clinical development of sitagliptin continues , additional studies have been completed , and more patients have been exposed to sitagliptin . The purpose of the present analysis is to up date the safety and tolerability assessment of sitagliptin by pooling data from 19 double-blind clinical studies . Methods The present analysis included data from 10,246 patients with type 2 diabetes who received either sitagliptin 100 mg/day ( N = 5,429 ; sitagliptin group ) or a comparator agent ( placebo or an active comparator ) ( N = 4,817 ; non-exposed group ) . The 19 studies from which this pooled population was drawn represent the double-blind , r and omized studies that included patients treated with the usual clinical dose of sitagliptin ( 100 mg/day ) for between 12 weeks and 2 years and for which results were available as of July 2009 . These 19 studies assessed sitagliptin taken as monotherapy , initial combination therapy with metformin or pioglitazone , or as add-on combination therapy with other antihyperglycemic agents ( metformin , pioglitazone , a sulfonylurea ± metformin , insulin ± metformin , or rosiglitazone + metformin ) . Patients in the non-exposed group were taking placebo , metformin , pioglitazone , a sulfonylurea ± metformin , insulin ± metformin , or rosiglitazone + metformin . The analysis used patient-level data from each study to evaluate between-group differences in the exposure-adjusted incidence rates of adverse events . Results Summary measures of overall adverse events were similar in the sitagliptin and non-exposed groups , except for an increased incidence of drug-related adverse events in the non-exposed group . Incidence rates of specific adverse events were also generally similar between the two groups , except for increased incidence rates of hypoglycemia , related to the greater use of a sulfonylurea , and diarrhea , related to the greater use of metformin , in the non-exposed group and constipation in the sitagliptin group . Treatment with sitagliptin was not associated with an increased risk of major adverse cardiovascular events . Conclusions In this up date d pooled safety analysis of data from 10,246 patients with type 2 diabetes  , sitagliptin 100 mg/day was generally well tolerated in clinical trials of up to 2 years in duration AIM The efficacy and safety of sitagliptin ( SITA ) monotherapy and SITA/metformin ( MET ) vs. pioglitazone ( PIO ) were assessed in patients with type 2 diabetes and moderate-to-severe hyperglycaemia ( A1C = 7.5 - 12.0 % ) . METHODS In an initial 12-week phase ( Phase A ) , 492 patients were r and omised 1 : 1 in a double-blind fashion to SITA ( 100 mg qd ) or PIO ( 15 mg qd , up-titrated to 30 mg after 6 weeks ) . In Phase B ( 28 additional weeks ) , the SITA group was switched to SITA/MET ( up-titrated to 50/1000 mg bid over 4 weeks ) and the PIO group was up-titrated to 45 mg qd RESULTS At the end of Phase A , mean changes from baseline were -1.0 % and -0.9 % for A1C ; -26.6 mg/dl and -28.0 mg/dl for fasting plasma glucose ; and -52.8 mg/dl and -50.1 mg/dl for 2-h post-meal glucose for SITA and PIO , respectively . At the end of Phase B , improvements in glycaemic parameters were greater with SITA/MET vs. PIO : -1.7 % vs. -1.4 % for A1C ( p = 0.002 ) ; -45.8 mg/dl vs. -37.6 mg/dl for fasting plasma glucose ( p = 0.03 ) ; -90.3 mg/dl vs. -69.1 mg/dl for 2-h postmeal glucose ( p = 0.001 ) ; and 55.0 % vs. 40.5 % for patients with A1C < 7 % ( p = 0.004 ) . A numerically higher incidence of gastrointestinal adverse events and a significantly lower incidence of oedema were observed with SITA/MET vs. PIO . The incidence of hypoglycaemia was similarly low in both groups . Body weight decreased with SITA/MET and increased with PIO ( -1.1 kg vs. 3.4 kg ; p < 0.001 ) . CONCLUSION Improvements in glycaemic control were greater with SITA/MET vs. PIO , with weight loss vs. weight gain . Both treatments were generally well tolerated AIMS This study was conducted to compare the glycaemic efficacy and safety of initial combination therapy with the fixed-dose combination of sitagliptin and metformin versus metformin monotherapy in drug-naive patients with type 2 diabetes . METHODS This double-blind study ( 18-week Phase A and 26-week Phase B ) r and omized 1250 drug-naÏve patients with type 2 diabetes [ mean baseline haemoglobin A1c ( HbA1c ) 9.9 % ] to sitagliptin/metformin 50/500 mg bid or metformin 500 mg bid ( uptitrated over 4 weeks to achieve maximum doses of sitagliptin/metformin 50/1000 mg bid or metformin 1000 bid ) . Results of the primary efficacy endpoint ( mean HbA1c reductions from baseline at the end of Phase A ) are reported herein . RESULTS At week 18 , mean change from baseline HbA1c was -2.4 % for sitagliptin/metformin FDC and -1.8 % for metformin monotherapy ( p < 0.001 ) ; more patients treated with sitagliptin/metformin FDC had an HbA1c value < 7 % ( p < 0.001 ) versus metformin monotherapy . Changes in fasting plasma glucose were significantly greater with sitagliptin/metformin FDC ( -3.8 mmol/l ) versus metformin monotherapy ( -3.0 mmol/l ; p < 0.001 ) . Homeostasis model assessment of β-cell function ( HOMA-β ) and fasting proinsulin/insulin ratio were significantly improved with sitagliptin/metformin FDC versus metformin monotherapy . Baseline body weight was reduced by 1.6 kg in each group . Both treatments were generally well tolerated with a low and similar incidence of hypoglycaemia . Abdominal pain ( 1.1 and 3.9 % ; p = 0.002 ) and diarrhoea ( 12.0 and 16.6 % ; p = 0.021 ) occurred significantly less with sitagliptin/metformin FDC versus metformin monotherapy ; the incidence of nausea and vomiting was similar in both groups . CONCLUSION Compared with metformin monotherapy , initial treatment with sitagliptin/metformin FDC provided superior glycaemic improvement with a similar degree of weight loss and lower incidences of abdominal pain and diarrhoea Abstract Introduction We evaluated the tolerability and efficacy of the addition of sitagliptin in Chinese patients with type 2 diabetes mellitus receiving stable insulin therapy alone or in combination with metformin . Material s and Methods A total of 467 patients with inadequate glycemic control on insulin ( glycated hemoglobin [ HbA1c ] ≥7.5 % and ≤11 % ) were r and omized 1:1 to receive sitagliptin 100 mg once daily or a matching placebo for 24 weeks . R and omization was stratified based on metformin use ( on or not on metformin ) and type of insulin ( pre‐mixed vs intermediate‐/long‐acting ) at screening . The primary end‐point was the change from baseline at week 24 in HbA1c . Results The addition of sitagliptin led to a significantly ( P < 0.001 ) greater week 24 HbA1c reduction ( 0.7 % ) compared with the reduction ( 0.3 % ) with placebo . A significantly ( P = 0.013 ) greater proportion of patients taking sitagliptin ( 16 % ) had an HbA1c of < 7.0 % at week 24 compared with placebo ( 8 % ) . The addition of sitagliptin significantly ( P < 0.001 ) reduced 2‐h post‐meal glucose by 26.5 mg/dL ( 1.5 mmol/L ) relative to placebo . Reductions from baseline in fasting plasma glucose were observed in both the sitagliptin ( 14.4 mg/dL reduction ) and placebo ( 10.7 mg/dL reduction ) groups ; the between‐group difference was not significant . A total of 64 ( 27.4 % ) patients taking sitagliptin and 51 ( 21.9 % ) taking placebo experienced adverse events of hypoglycemia ( symptomatic or asymptomatic ) . Neither group had a significant change from baseline in bodyweight . Conclusions After 24 weeks , sitagliptin added to stable insulin therapy ( ±metformin ) was generally well tolerated and improved glycemic control in Chinese patients with type 2 diabetes mellitus BACKGROUND Type 2 diabetes mellitus ( T2DM ) is a significant burden in China , where approximately 114 million patients have been diagnosed with diabetes . Chinese patients present with prominent β-cell failure , with result ing deficiency in insulin secretion , particularly early phase insulin secretion leading to postpr and ial hyperglycemia . Sitagliptin , a selective once-daily oral dipeptidyl peptidase-4 inhibitor , has been shown to improve glycemic control as monotherapy and in combination with other antihyperglycemic agents , including sulfonylureas and metformin . METHODS This was a multicenter r and omized double-blind placebo-controlled study conducted in China . The study assessed the safety and efficacy of the addition of sitagliptin 100 mg once daily versus placebo on changes from baseline at Week 24 in HbA1c , fasting plasma glucose ( FPG ) and 2-h post-meal glucose ( PMG ) . Patients were aged 18 - 79 years , had T2DM with inadequate glycemic control , and were taking a sulfonylurea , with or without metformin . RESULTS After 24 weeks , sitagliptin  reduced HbA1c , FPG , and 2-h PMG significantly more than placebo ( between-treatment differences : -0.61 % , -16.8 mg/dL , and -32.9 mg/dL , respectively ; P < 0.001 for all ) . The addition of sitagliptin was generally well tolerated , with a comparable incidence of adverse events and drug-related adverse events in both treatment groups . The sitagliptin group had a higher incidence of symptomatic hypoglycemia than the placebo group ( 25/248 [ 10.1 % ] vs 13/249 [ 5.2 % ] , respectively ; P = 0.042 ) . CONCLUSIONS Sitagliptin 100 mg once daily significantly improved glycemic control in Chinese patients with T2DM who had inadequate glycemic control with sulfonylurea , with or without metformin therapy . The addition of sitagliptin was generally well tolerated . ( clinical trials.gov : NCT01590771 ) OBJECTIVE To evaluate the efficacy and tolerability of sitagliptin when added to insulin therapy alone or in combination with metformin in patients with type 2 diabetes . METHODS After a 2 week placebo run-in period , eligible patients inadequately controlled on long-acting , intermediate-acting or premixed insulin ( HbA1c > or = 7.5 % and < or = 11 % ) , were r and omised 1:1 to the addition of once-daily sitagliptin 100 mg or matching placebo over a 24-week study period . The study capped the proportion of r and omised patients on insulin plus metformin at 75 % . Further , the study capped the proportion of r and omised patients on premixed insulin at 25 % . The metformin dose and the insulin dose were to remain stable throughout the study . The primary endpoint was HbA1c change from baseline at week 24 . RESULTS Mean baseline characteristics were similar between the  sitagliptin ( n = 322 ) and placebo ( n = 319 ) groups , including HbA1c ( 8.7 vs. 8.6 % ) , diabetes duration ( 13 vs. 12 years ) , body mass index ( 31.4 vs. 31.4 kg/m(2 ) ) , and total daily insulin dose (  
    Output:
    
These results demonstrated that sitagliptin did not increase the risk of cardiovascular events in patients with T2DM