***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 Traditional blood glucose – lowering agents do not sustain adequate glycemic control in most type 2 diabetic patients . Pre clinical studies with exenatide have suggested sustained improvements in β-cell function . We investigated the effects of 52 weeks of treatment with exenatide or insulin glargine followed by an off-drug period on hyperglycemic clamp – derived measures of β-cell function , glycemic control , and body weight . RESEARCH DESIGN AND METHODS Sixty-nine metformin-treated patients with type 2 diabetes were r and omly assigned to exenatide ( n = 36 ) or insulin glargine ( n = 33 ) . β-Cell function was measured during an arginine-stimulated hyperglycemic clamp at week 0 , at week 52 , and after a 4-week off-drug period . Additional end points included effects on glycemic control , body weight , and safety . RESULTS Treatment-induced change in combined glucose- and arginine-stimulated C-peptide secretion was 2.46-fold ( 95 % CI 2.09–2.90 , P < 0.0001 ) greater after a 52-week exenatide treatment compared with insulin glargine treatment . Both exenatide and insulin glargine reduced A1C similarly : −0.8 ± 0.1 and −0.7 ± 0.2 % , respectively ( P = 0.55 ) . Exenatide  reduced body weight compared with insulin glargine ( difference −4.6 kg , P < 0.0001 ) . β-Cell function measures returned to pretreatment values in both groups after a 4-week off-drug period . A1C and body weight rose to pretreatment values 12 weeks after discontinuation of either exenatide or insulin glargine therapy . CONCLUSIONS Exenatide  significantly improves β-cell function during 1 year of treatment compared with titrated insulin glargine . After cessation of both exenatide and insulin glargine  therapy , β-cell function and glycemic control returned to pretreatment values , suggesting that ongoing treatment is necessary to maintain the beneficial effects of either therapy OBJECTIVE To determine the safety and efficacy of the long-acting analog insulin glargine compared with NPH insulin in patients with type 2 diabetes who were previously treated with insulin alone . RESEARCH DESIGN AND METHODS A total of 518 subjects with type 2 diabetes who were receiving NPH insulin with or without regular insulin for postpr and ial control were r and omized to receive insulin glargine ( HOE 901 ) once daily ( n = 259 ) or NPH insulin once or twice daily in = 259 ) for 28 weeks in an open-label , multicenter trial . Doses were adjusted to obtain target fasting glucose < 6.7 mmol/l . At study end point , the median total daily insulin dose in both treatment groups was 0.75 IU/kg . RESULTS The treatment groups showed similar improvements in HbA1c from baseline to end point on intent-to-treat analysis . The mean change ( means + /- SD ) in HbA1c from baseline to end point was similar in the insulin glargine group ( -0.41 + /- 0.1 % ) and the NPH group ( -0.59 + /- 0.1 % ) after patients began with an average baseline HbA1c of approximately 8.5 % . The treatments were associated with similar reductions in fasting glucose levels . Overall , mild symptomatic hypoglycemia was similar in insulin glargine subjects ( 61.4 % ) and NPH insulin subjects ( 66.% ) However , nocturnal hypoglycemia in the insulin glargine group was reduced by 25 % during the treatment period after the dose-titration phase(26.5 vs. 35.5 % , P = 0.0136 ) . Subjects in the insulin glargine group experienced less weight gain than those in the NPH group ( 0.4 vs. 1.4 kg , P < 0.0007 ) . CONCLUSIONS In patients with type 2 diabetes , once-daily bedtime insulin glargine is as effective as once- or twice-daily NPH in improving and maintaining glycemic control . In addition , insulin glargine deonstrates a lower risk of nocturnal hypoglycemia and less weight gain compared with NPH insulin Aims /hypothesisThe aim of the study was to compare the efficacy and safety of liraglutide in type 2 diabetes mellitus vs placebo and insulin glargine ( A21Gly , B31Arg , B32Arg human insulin ) , all in combination with metformin and glimepiride . Methods This r and omised ( using a telephone or web-based r and omisation system ) , parallel-group , controlled 26 week trial of 581 patients with type 2 diabetes mellitus on prior monotherapy ( HbA1c 7.5–10 % ) and combination therapy ( 7.0–10 % ) was conducted in 107 centres in 17 countries . The primary endpoint was HbA1c .  Patients were r and omised ( 2:1:2 ) to liraglutide 1.8 mg once daily ( n = 232 )  , liraglutide placebo ( n = 115 ) and open-label insulin glargine ( n = 234 ) , all in combination with metformin ( 1 g twice daily ) and glimepiride ( 4 mg once daily ) . Investigators , participants and study monitors were blinded to the treatment status of the liraglutide and placebo groups at all times . Results The number of patients analysed as intention to treat were : liraglutide n = 230 , placebo n = 114 , insulin glargine n = 232 . Liraglutide reduced HbA1c significantly vs glargine ( 1.33 % vs 1.09 % ; −0.24 % difference , 95 % CI 0.08 , 0.39 ; p = 0.0015 ) and placebo ( −1.09 % difference , 95 % CI 0.90 , 1.28 ; p < 0.0001 ) . There was greater weight loss with liraglutide vs placebo ( treatment difference –1.39 kg , 95 % CI 2.10 , 0.69 ; p = 0.0001 ) , and vs glargine ( treatment difference −3.43 kg , 95 % CI 4.00 , 2.86 ; p < 0.0001 ) . Liraglutide reduced systolic BP ( −4.0 mmHg ) vs glargine ( + 0.5 mmHg ; −4.5 mmHg difference , 95 % CI 6.8 , −2.2 ; p = 0.0001 ) but not vs placebo ( p = 0.0791 ) . Rates of hypoglycaemic episodes ( major , minor and symptoms only , respectively ) were 0.06 , 1.2 and 1.0 events/patient/year , respectively , in the liraglutide group ( vs 0 , 1.3 , 1.8 and 0 , 1.0 , 0.5 with glargine and placebo , respectively ) . A slightly higher number of adverse events ( including nausea at 14 % ) were reported with liraglutide , but only 9.8 % of participants in the group receiving liraglutide developed anti-liraglutide antibodies . Conclusions /interpretationLiraglutide added to metformin and sulfonylurea produced significant improvement in glycaemic control and bodyweight compared with placebo and insulin glargine . The difference vs insulin glargine in HbA1c was within the predefined non-inferiority margin . Trial registration : Clinical Trials.gov NCT00331851 Funding : The study was funded by Novo Nordisk Context Are both exenatide and insulin glargine reasonable additions for patients with type 2 diabetes that is suboptimally controlled despite metformin and sulfonylurea therapy ? Contribution This multicenter , 26-week , r and omized trial compared the addition of exenatide or insulin glargine to regimens of 551 patients with suboptimally controlled type 2 diabetes . Both additions led to similar reductions in hemoglobin A1c levels .  Exenatide best reduced postpr and ial glucose excursions ;  insulin glargine best reduced fasting glucose concentrations . Exenatide patients experienced weight loss and increased gastrointestinal symptoms , such as nausea and vomiting . Implication s Adding either exenatide or insulin glargine to oral hypoglycemic regimens may improve glycemic control in patients with suboptimally controlled type 2 diabetes . The Editors Progressive -cell dysfunction and insulin resistance are the core defects of type 2 diabetes , result ing in hyperglycemia and a host of devastating microvascular and cardiovascular complications . When diet and exercise modifications no longer maintain glycemic targets , oral blood glucoselowering drugs are usually administered . However , the long-term effectiveness of these drugs can be unsatisfactory because of modest or short-lived efficacy , adverse effects and tolerability issues , and an inability to affect the progressive decline in -cell function ( 1 ) . When 1 or more oral blood glucoselowering drugs no longer adequately control escalating hyperglycemia , addition of basal insulin is common practice ( 2 ) . Although basal insulin can improve glycemic control , its use can be complicated by inadequate control of postpr and ial hyperglycemia , an increased risk for hypoglycemia compared with that observed with oral blood glucoselowering drugs alone , and the need for complicated dose-titration regimens ( 3 , 4 ) . In addition , insulin therapy often causes weight gain , compounding any preexisting obesitya common contributing factor to insulin resistance that is difficult to manage effectively ( 5 - 7 ) . A recent advance in insulin therapy was the introduction of insulin glargine , an analogue of human insulin design ed to have an extended duration of action ( 8) . Titrated to target fasting glucose levels ( treat-to-target ) , insulin glargine provides greater convenience and reduced incidence of hypoglycemia than neutral protamine Hagedorn ( NPH ) insulin ( 9 - 16 ) . However , insulin glargine still maintains many drawbacks of insulin therapy , including the need for dose titration , increased hypoglycemia , weight gain , and the persistence of postpr and ial glucose excursions ( 9 - 16 ) . Glucagon-like peptide-1 ( GLP-1 ) , an incretin hormone , is an essential component of normal glucose homeostasis ( 17 ) . The actions of GLP-1 include enhancement of glucose-dependent insulin secretion and regulation of glucagon release and the rate of gastric emptying , thereby reducing hyperglycemia ( 18 ) . In addition , GLP-1 enhances -cell function and promotes satiety , result ing in reduced caloric intake and weight reduction ( 18 ) . These activities have generated interest in GLP-1 as a potential therapy for diabetes . However , GLP-1 is rapidly inactivated by dipeptidyl peptidase-IV , and the active forms of GLP-1 have a circulating half-life of only 1 to 2 minutes ( 19 ) . The limited duration of action for exogenously administered GLP-1 limits its utility in a chronic disease like type 2 diabetes . Therefore , agents that may mimic or enhance the activities of GLP-1 are of great clinical interest . The incretin mimetics are an emerging class of compounds that elicit glucoregulatory actions similar to those of GLP-1 . Exenatide ( exendin-4 ) , a 39amino acid peptide that belongs to this class , shares many of the same glucoregulatory , -cell , and body weight effects that have been observed with GLP-1 ( 18 , 20 - 23 ) . However , exenatide is resistant to degradation by dipeptidyl peptidase-IV and has a pharmacokinetic profile that is more amenable to long-term administration . Exenatide injection is approved by the U.S. Food and Drug Administration as adjunctive therapy to improve glycemic control in patients with type 2 diabetes who are taking metformin , a sulfonylurea , or a combination of metformin and a sulfonylurea but have not achieved adequate glycemic control . In phase 3 , 30-week controlled clinical trials , exenatide improved glycemic control ( as demonstrated by statistically significant reductions in fasting and postpr and ial plasma glucose levels and hemoglobin A1c levels ) and reduced body weight compared with placebo in patients with inadequately controlled type 2 diabetes ( 20 - 22 ) . Given the effects of exenatide in these clinical trials and the common practice of adding basal insulin to existing regimens of oral agents , we design ed our study to compare the effects of adding either exenatide or insulin glargine to treatment regimens of patients whose blood glucose levels were inadequately controlled with oral agents alone . Methods Study Protocol The primary objective of our r and omized , open-label , phase  
    Output:
    
GLP-1RA showed equivalent or superior efficacy to IGlar for reducing hemoglobin A1c ( HbA1c ) , with a greater proportion of patients achieving HbAlc<7 % .
GLP-1RA also favored decreased body weight , total cholesterol ( TC ) , low-density lipoprotein ( LDL ) , and systolic blood pressure ( SBP ) .
Serious adverse events were uncommon and not significantly different .
More patients taking GLP-1RA experienced gastrointestinal complications : nausea , diarrhea , and vomiting .
Severe hypoglycemia events were rare , and minor hypoglycemia was less common for GLP-1RA .
CONCLUSIONS GLP-1RA showed greater efficacy compared to IGlar for type 2 diabetes , and it may also prove beneficial for other diabetes-associated characteristics , including obesity , hypertension , and hyperlipidemia