***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 whether addition of three different doses of liraglutide to insulin in patients with type 1 diabetes ( T1D ) results in significant reduction in glycemia , body weight , and insulin dose . RESEARCH DESIGN AND METHODS We r and omized 72 patients ( placebo = 18 , liraglutide = 54 ) with T1D to receive placebo and 0.6 , 1.2 , and 1.8  mg liraglutide daily for 12 weeks . RESULTS In the 1.2-mg and 1.8-mg groups , the mean weekly reduction in average blood glucose was −0.55 ± 0.11 mmol/L ( 10 ± 2 mg/dL ) and −0.55 ± 0.05 mmol/L ( 10 ± 1 mg/dL ) , respectively ( P < 0.0001 ) , while it remained unchanged in the 0.6-mg and placebo groups . In the 1.2-mg group , HbA1c fell significantly ( −0.78 ± 15 % , −8.5 ± 1.6 mmol/mol , P < 0.01 ) , while it did not in the 1.8-mg group ( −0.42 ± 0.15 % , −4.6 ± 1.6 mmol/mol , P = 0.39 ) and 0.6-mg group ( −0.26 ± 0.17 % , −2.8 ± 1.9 mmol/mol , P = 0.81 ) vs. the placebo group ( −0.3 ± 0.15 % , −3.3 ± 1.6 mmol/mol ) . Glycemic variability was reduced by 5 ± 1 % ( P < 0.01 ) in the 1.2-mg group only . Total daily insulin dose fell significantly only in the 1.2-mg and 1.8-mg groups ( P < 0.05 ) . There was a 5 ± 1 kg weight loss in the two higher-dose groups ( P < 0.05 ) and by 2.7 ± 0.6 kg ( P < 0.01 ) in the 0.6-mg group vs. none in the placebo group . In the 1.2- and 1.8-mg groups , postpr and ial plasma glucagon concentration fell by 72 ± 12 % and 47 ± 12 % , respectively ( P < 0.05 ) . Liraglutide led to higher gastrointestinal adverse events ( P < 0.05 ) and ≤1 % increases ( not significant ) in percent time spent in hypoglycemia ( < 55 mg/dL , 3.05 mmol/L ) . CONCLUSIONS Addition of 1.2 mg and 1.8 mg liraglutide to insulin over a 12-week period in overweight and obese patients with T1D results in modest reductions of weekly mean glucose levels with significant weight loss , small insulin dose reductions , and frequent gastrointestinal side effects . These findings do not justify the use of liraglutide in all patients with T1D Summary Background Type 1 diabetes results from autoimmune destruction of pancreatic β cells . Findings from pre clinical studies suggest that dipeptidyl peptidase-4 inhibitors and proton-pump inhibitors might enhance β-cell survival and regeneration . We postulated that sitagliptin and lansoprazole would preserve β-cell function in patients with recent-onset type 1 diabetes . Methods We did a double-blind , placebo-controlled , phase 2 trial ( REPAIR-T1D ) . Participants aged 11–36 years , diagnosed with type 1 diabetes within the past 6 months were recruited from Sanford Health Systems ( Sioux Falls , SD , USA ; Fargo , ND , USA ) , Children 's Hospitals and Clinics of Minnesota ( St Paul , MN , USA ) , and Rady Children 's Hospital ( San Diego , CA , USA ) . Participants were r and omly assigned ( 2:1 ) to receive oral sitagliptin ( 100 mg for participants ≥18 years , 50 mg for those < 18 years ) and lansoprazole ( 60 mg for participants ≥18 years , 30 mg for those < 18 years ) or matched placebo for 12 months . R and omisation was done by a blocked r and omisation process ( blocks of three and six ) , with separate streams for younger ( < 18 years ) and older ( ≥18 years ) participants , and males and females . All participants and personnel remained masked until after the completion of the final 12 month visit , at which time data were unmasked to the analysis team . The primary endpoint was C-peptide response to a mixed meal challenge at 12 months measured as 2 h area under curve . Analysis was by intention to treat . This trial is registered with Clinical Trials.gov , number NCT01155284 . Findings Between Sept 21 , 2010 , and May 29 , 2012 , 46 participants were r and omly assigned to the treatment group and 22 to the placebo group ; of whom 40 participants in the treatment group and 18 in the placebo group completed the 12-month treatment . At 12 months , the mean change in C-peptide area under curve was −229 pmol/L ( 95 % CI −316 to −142 ) for the treatment group and −253 pmol/L ( −383 to −123 ) for the placebo group ; this difference was not significant ( p=0·77 ) . No adverse or serious adverse events were probably or definitely related to the study treatment . Interpretation Although the expected change in the primary endpoint was not achieved , not all participants had increases in glucagon-like peptide-1 and gastrin concentrations that were expected with treatment . Although participants did not have adverse events related to study drugs , the study is not powered to address safety definitively . Further trials including these drugs might be warranted , but should be design ed to ensure appropriate selection of participants and increases in these intermediary hormones . Funding Sanford Research and JDRF Incretin based therapies are known to have pleotropic benefits in type 2 diabetes but have not been studied in new onset type 1 diabetes . In this r and omized , open label study , we investigated the effect of the addition of exenatide or sitagliptin to insulin in patients with new onset type 1 diabetes . Our data suggest that the addition of exenatide and sitagliptin decreases insulin requirements without increasing endogenous insulin production and hypoglycemic events BACKGROUND The combination of insulin and glucagon-like peptide-1 ( GLP-1 ) receptor agonist therapy improves glycaemic control , induces weight loss , and reduces insulin dose needed in type 2 diabetes . We assessed the efficacy and safety of the GLP-1 receptor agonist liraglutide as an add-on therapy to insulin for overweight adult patients with type 1 diabetes . METHODS We did a r and omised , double-blind , placebo-controlled trial at Steno Diabetes Center ( Gentofte , Denmark ) . Patients aged 18 years or older with type 1 diabetes , insufficient glycaemic control ( HbA1c > 8 % [ 64 mmol/mol ] ) , and overweight ( BMI > 25 kg/m(2 ) ) were r and omly assigned ( 1:1 ) to receive insulin treatment plus either liraglutide or placebo ( saline solution ) by subcutaneous injection once per day . R and omisation was done in blocks of four . Treatment assignment was masked to investigators and patients . Treatment lasted 24 weeks and liraglutide was started at a dose of 0·6 mg per day , escalated to 1·2 mg per day after 1 week , and then again to 1·8 mg per day after another week . Intervals between dose increments could be extended at the discretion of the investigator . The primary endpoint was change in HbA1c from baseline to week 24 . Secondary endpoints were changes in hypoglycaemic events , glycaemic variability , glycaemic excursions , insulin dose , bodyweight , postpr and ial plasma concentrations of glucagon and GLP-1 , gastric emptying , blood pressure , heart rate , patient-reported outcome measures , time spent in hypoglycaemia , near-normoglycaemia , and hyperglycaemia , plasma fasting glucose , mean glucose , and cholesterol . Efficacy analyses were calculated by use of a mixed model , whereby a patient 's data are used as long as the patient is in the study . The safety analyses were done in the intention-to-treat population , which consisted of all patients who received at least one dose of their r and omly assigned study drug . This study is registered with Clinical Trials.gov , number NCT01612468 . FINDINGS Between July 10 , 2012 , and May 30 , 2014 , we enrolled 100 patients with type 1 diabetes , with 50 patients allocated liraglutide and 50 to placebo .  Four patients from the liraglutide group and six patients from the placebo group discontinued treatment before 24 weeks . At the end of treatment , change in HbA1c from baseline did not differ between groups ( -0·5 % , 95 % CI -0·8 to -0·4 [ -6·0 mmol/mol , 95 % CI -8·7 to -4·4 ] with liraglutide vs -0·3 % , -0·6 to -0·2 [ -4·0 mmol/mol , -6·6 to -2·3 ] with placebo ; between-group difference -0·2 % [ -0·5 to 0·1 ; 2·2 mmol/mol , -5·5 to 1·1 ] , p=0·1833 ) . The number of hypoglycaemic events was reduced with liraglutide , with an incident rate ratio of 0·82 ( 95 % CI 0·74 to 0·90 ) . However , we detected no changes in glycaemic variability ( continuous overall net glycaemic action per 60 min from 10·3 [ 95 % CI 9·8 to 10·8 ] to 9·9 [ 9·2 to 10·6 ] in the liraglutide treated patients vs 10·2 [ 9·7 to 10·7 ] to 9·7 [ 9·1 to 10·3 ] in the placebo treated patients ) . Both bolus insulin ( difference -5·8 IU , 95 % CI -10·7 to -0·8 , p=0·0227 ) and bodyweight ( difference -6·8 kg , 95 % CI -12·2 to -1·4 , p=0·0145 ) decreased with liraglutide treatment compared with  placebo . Heart rate increased with liraglutide , with a difference between groups of 7·5 bpm ( 95 % CI 2·8 - 12·2 , p=0·0019 ) . Postpr and ial plasma glucagon and GLP-1 concentrations did not differ between groups ( difference between groups at end of treatment : -408 mmol/L per 240 min [ 95 % CI -941 to 125 , p=0·1309 ] for glucagon and -266 mmol/L per 240 min [ -1034 to 501 , p=0·4899 ] for GLP-1 ) . Gastric emptying was delayed after 3 weeks of treatment with liraglutide ( 19·9 min , 95 % CI 0·8 to 39·0 , p=0·0412 ) , but we detected no difference after 24 weeks of treatment ( -1·5 min , -20·5 to 17·6 , p=0·8793 ) . Patient-reported outcome measures differed between groups only with respect to perceived frequency of hypoglycaemia , which was higher with placebo , with a difference between groups of -0·6 ( 95 % CI -1·1 to -0·07 ,  p=0·0257 ) . Liraglutide was associated with more frequent nausea ( 29 [ 58 % ] patients with liraglutide vs five [ 10 % ] with placebo ) , dyspepsia ( 11 [ 22 % ] patients with liraglutide vs one [ 2 % ] with placebo ) , diarrhoea ( ten [ 20 % ] patients with liraglutide vs one [ 2 % ] with placebo ) , decreased appetite ( seven patients [ 14 % ] with liraglutide vs none with placebo ) , and vomiting ( seven [ 14 % ] patients with liraglutide vs one [ 2 % ] with placebo ) . INTERPRETATION In patients with type 1 diabetes , overweight , and insufficient glycaemic control , the reduction in HbA1c did not differ between insulin plus placebo and insulin plus liraglutide treatment . Liraglutide was associated with reductions in hypoglycaemic events , bolus and total insulin dose , and bodyweight , and increased heart rate . FUNDING Novo Nordisk OBJECTIVE To investigate the effect of 4 weeks of treatment with liraglutide on  insulin dose and glycemic control in type 1 diabetic patients with and without residual β-cell function . 
    Output:
    
CONCLUSIONS Incretin-based treatment in patients with T1DM may improve glycemic control and reduce insulin dose and weight without increasing the risk of serious adverse event , such as severe hypoglycemia , ketosis or ketoacidosis .