***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: Abbreviations ACCORD Action to Control Cardiovascular Risk in Diabetes ADVANCE Action in Diabetes and Vascular Disease : Preterax and Diamicron Modified-Release Controlled Evaluation AGI α-Glucosidase inhibitor  CAD Coronary artery disease CKD Chronic kidney disease CVD Cardiovascular disease DPP-4 Dipeptidyl peptidase IV GIP Glucose-dependent insulinotropic peptide GLP-1 Glucagon-like peptide 1 NPH Neutral protamine Hagedorn TZD Thiazolidinedione UKPDS UK Prospect i ve Diabetes Study VADT Veterans Affairs Diabetes Background For patients with type 2 diabetes who are uncontrolled on a combination of two oral antidiabetic agents , addition of the long-acting basal insulin glargine is a well established treatment option . However , data on the efficacy and safety of a combination of metformin , a dipeptidyl peptidase-4 ( DPP-4 ) inhibitor , and insulin glargine are limited in real-world setting s. Therefore , the aim of this study was to analyze blood glucose control , rates of hypoglycemia and body weight in a large cohort of patients with type 2 diabetes treated with this combination therapy in real practice . Methods This noninterventional , multicenter , prospect i ve , observational trial with a follow-up of 20 weeks enrolled insulin-naïve patients who had been on a stable fixed dose of metformin and a DPP-4 inhibitor for at least 3 months , and had a glycosylated hemoglobin ( HbA1c ) between 7.5 % and 10 % . Patients were selected at the investigators ’ discretion for initiation of insulin glargine at baseline . A total of 1,483 patients were included , of whom 1,262 were considered to be the efficacy set . Primary efficacy parameters were HbA1c and fasting plasma glucose . Secondary outcome measures included achievement of glycemic targets , body weight , rates of hypoglycemia , and other safety parameters , as well as re source consumption . Results Upon initiation of insulin glargine , mean HbA1c decreased from 8.51 % to 7.36 % ( −1.15%±0.91 % ; 95 % confidence interval [ CI ] −1.20 to −1.10 ) . An HbA1c level < 6.5 % was achieved in 8.2 % of patients and a level < 7.0 % in 31.5 % . Mean fasting plasma glucose decreased from 174±47 mg/dL to 127±31 mg/dL ( −47.3±44.1 mg/dL ; 95 % CI −49.8 to −44.8 ) . In 11.9 % of patients , a fasting plasma glucose level < 100 mg/dL was achieved . Bodyweight decreased on average by 0.98±3.90 kg ( 95 % CI 1.19–0.76 ) . Hypoglycemia ( blood glucose ≤70 mg/dL ) was observed in 29 patients ( 2.30 % ) , of whom six ( 0.48 % ) had nocturnal hypoglycemia and four ( 0.32 % ) had documented severe events ( blood glucose < 56 mg/dL ) . Conclusion The results of this observational study show that insulin glargine , when added to a fixed-dose combination of metformin and a DPP-4 inhibitor , result ed in a significant and clinical ly relevant improvement of glycemic control . Importantly , this intervention did not interfere with the action of the DPP-4 inhibitors , result ing in neutral effects on weight and low rates of hypoglycemia . We conclude that this treatment intensification approach may be useful , efficient , and safe in daily clinical practice for patients with type 2 diabetes Aims /hypothesisType 2 diabetes is difficult to manage in patients with a long history of disease requiring insulin therapy .  Moreover , addition of most currently available oral antidiabetic agents increases the risk of hypoglycaemia . Vildagliptin is a dipeptidyl peptidase-IV inhibitor , which improves glycaemic control by increasing pancreatic beta cell responsiveness to glucose and suppressing inappropriate glucagon secretion . This study assessed the efficacy and tolerability of vildagliptin added to insulin therapy in patients with type 2 diabetes . Material s and methods This was a multicentre , 24-week , double-blind , r and omised , placebo-controlled , parallel-group study in patients with type 2 diabetes that was inadequately controlled ( HbA1c = 7.5–11 % ) by insulin . Patients received vildagliptin ( n = 144 ; 50 mg twice daily ) or placebo ( n = 152 ) while continuing insulin therapy . Results Baseline HbA1c averaged 8.4 ± 0.1 % in both groups . The adjusted mean change from baseline to endpoint ( AMΔ ) in HbA1c was −0.5 ± 0.1 % and −0.2 ± 0.1 % in patients receiving vildagliptin or placebo , respectively , with a significant between-treatment difference ( p = 0.01 ) . In patients aged ≥65 years  , the AMΔ HbA1c was −0.7 ± 0.1 % in the vildagliptin group vs −0.1 ± 0.1 % in the placebo group ( p < 0.001 ) . The incidence of adverse events was similar in the vildagliptin ( 81.3 % ) and placebo ( 82.9 % ) groups . However , hypoglycaemic events were less common ( p < 0.001 ) and less severe ( p < 0.05 ) in patients receiving vildagliptin than in those receiving placebo . Conclusions /interpretationVildagliptin decreases HbA1c in patients whose type 2 diabetes is poorly controlled with high doses of insulin . Addition of vildagliptin to insulin therapy is also associated with reduced confirmed and severe hypoglycaemia . Clinical Trials.gov ID no. : NCT 00099931 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 ( 51 vs. 52 IU ) , respectively . At 24 weeks , the addition of sitagliptin significantly ( p < 0.001 ) reduced HbA1c by 0.6 % compared with placebo ( 0.0 % ) . A greater proportion of patients achieved an HbA1c level < 7 % while r and omised to sitagliptin as compared with placebo ( 13 vs. 5 % respectively ; p < 0.001 ) . Similar HbA1c reductions were observed in the patient strata defined by insulin type ( long-acting and intermediate-acting insulins or premixed insulins ) and by baseline metformin treatment . The addition of sitagliptin significantly ( p < 0.001 ) reduced fasting plasma glucose by 15.0 mg/dl ( 0.8 mmol/l ) and 2-h postmeal glucose by 36.1 mg/dl ( 2.0 mmol/l ) relative to placebo . A higher incidence of adverse experiences was reported with sitagliptin ( 52 % ) compared with placebo ( 43 % ) , due mainly to the increased incidence of hypoglycaemia ( sitagliptin , 16 % vs. placebo , 8 % ) . The number of hypoglycaemic events meeting the protocol -specified criteria for severity was low with sitagliptin ( n = 2 ) and placebo ( n = 1 ) . No significant change from baseline in body weight was observed in either group . CONCLUSION In this 24-week study , the addition of sitagliptin to ongoing , stable-dose insulin therapy with or without concomitant metformin improved glycaemic control and was generally well tolerated in patients with type 2 diabetes OBJECTIVE To evaluate the efficacy and long-term safety of linagliptin added to basal insulins in type 2 diabetes inadequately controlled on basal insulin with or without oral agents . RESEARCH DESIGN AND METHODS A total of 1,261 patients ( HbA1c ≥7.0 % [ 53 mmol/mol ] to ≤10.0 % [ 86 mmol/mol ] ) on basal insulin alone or combined with metformin and /or pioglitazone were r and omized ( 1:1 ) to double-blind treatment with linagliptin  5 mg once daily or placebo for ≥52 weeks . The basal insulin dose was kept unchanged for 24 weeks but could thereafter be titrated according to fasting plasma glucose levels at the investigators ’ discretion . The primary end point was the mean change in HbA1c from baseline to week 24 . The safety analysis incorporated data up to a maximum of 110 weeks . RESULTS At week 24 , HbA1c changed from a baseline of 8.3 % ( 67 mmol/mol ) by −0.6 % ( −6.6 mmol/mol ) and by 0.1 % ( 1.1 mmol/mol ) with linagliptin and placebo , respectively ( treatment difference −0.65 % [ 95 % CI −0.74 to −0.55 ] [ −7.1 mmol/mol ] ; P < 0.0001 ) . Despite the option to uptitrate basal insulin , it was adjusted only slightly upward ( week 52 , linagliptin 2.6 IU/day , placebo 4.2 IU/day ; P < 0.003 ) , result ing in no further HbA1c improvements . Frequencies of hypoglycemia ( week 24 , linagliptin 22.0 % , placebo 23.2 % ; treatment end , linagliptin 31.4 % , placebo 32.9 % ) and adverse events ( linagliptin 78.4 % , placebo 81.4 % ) were similar between groups . Mean body weight remained unchanged ( week 52 , linagliptin −0.30 kg , placebo −0.04 kg ) . CONCLUSIONS Linagliptin added to basal insulin therapy significantly improved glycemic control relative to placebo without increasing hypoglycemia or body weight AIM To assess whether there is a difference in the effects of vildagliptin and glimepiride on glucose fluctuation in patients with type 2 diabetes mellitus ( T2DM ) using continuous glucose monitoring ( CGM ) . METHODS This was an open-label , r and omized cross-over study conducted in T2DM patients . A total of 24 patients ( age : 58.3 ± 5.56 years , baseline HbA1c : 7.6 ± 0.50 % ) who were on stable metformin monotherapy ( 500 - 3000 mg ) were enrolled , and all completed the study . Each patient received two 5-day treatments ( vildagliptin 50 mg b.i.d . or glimepiride 2 mg q.d . ) in a cross-over manner . Various biomarkers and blood glucose concentrations were measured following breakfast . The 24-h glucose profiles were also measured using the CGM device at baseline and after 5 days of treatment , and fluctuations in glucose levels were estimated from CGM data . RESULTS Both vildagliptin and glimepiride  reduced postpr and ial glucose levels , based on both CGM data ( 15 % vs. 16 % ) and measured plasma glucose ( 13 % vs.17 % ) . Vildagliptin showed lower glucose fluctuations  than glimepiride as measured by mean amplitude of glycaemic excursions ( MAGE , p = 0.1076 ) , st and ard deviation ( s.d . , p = 0.1346 ) of blood glucose rate of change , but did not reach statistical significance attributed to the small sample size . MAGE was reduced by ∼20 % with vildagliptin versus glimepiride . Vildagliptin led to statistically significant lowering of the rate of change in the median curve ( RCMC ) and 
    Output:
    
Compared to placebo , DPP-4 inhibitors exhibit a better glycaemic control without further increasing the risk of weight gain and hypoglycaemia in patients with type 2 diabetes inadequately controlled with insulin