***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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    Input: In the present multicentre , open‐label , prospect i ve , phase III study , we evaluated the real‐world effectiveness and ease of use of nasal glucagon ( NG ) in the treatment of moderate/severe hypoglycaemic events ( HEs ) in adults with type 1 diabetes ( T1D ) . Patients and caregivers were taught how to use NG ( 3 mg ) to treat moderate/severe HEs , record the time taken to awaken or return to normal status , and measure blood glucose ( BG ) levels over time . Question naires were used to collect information about adverse events and ease of use of NG  . In the efficacy analysis population , 69 patients experienced 157 HEs . In 95.7 % patients , HEs resolved within 30 minutes of NG administration . In all the 12 severe HEs , patients awakened or returned to normal status within 15 minutes of NG administration without additional external medical help . Most caregivers reported that NG was easy to use . Most adverse events were local and of low to moderate severity . In this study , a single , 3‐mg dose of NG demonstrated real‐life effectiveness in treating moderate and severe HEs in adults with T1D .  NG was well tolerated and easy to use OBJECTIVE Treatment of severe hypoglycemia outside of the hospital setting is limited to intramuscular glucagon requiring reconstitution prior to injection . The current study examined the safety and dose-response relationships of a needle-free intranasal glucagon preparation in youth aged 4 to < 17 years . RESEARCH DESIGN AND METHODS A total of 48 youth with type 1 diabetes completed the study at seven clinical centers . Participants in the two youngest cohorts ( 4 to < 8 and 8 to < 12 years old ) were r and omly assigned to receive either 2 or 3 mg intranasal glucagon in two separate sessions or to receive a single , weight-based dose of intramuscular glucagon .  Participants aged 12 to < 17 years received 1 mg intramuscular glucagon in one session and 3 mg intranasal glucagon in the other session . Glucagon was given after glucose was lowered to < 80 mg/dL ( mean nadir ranged between 67 and 75 mg/dL ) . RESULTS All 24 intramuscular and 58 of the 59 intranasal doses produced a ≥25 mg/dL rise in glucose from nadir within 20 min of dosing . Times to peak plasma glucose and glucagon levels were similar under both intramuscular and intranasal conditions . Transient nausea occurred in 67 % of intramuscular sessions versus 42 % of intranasal sessions ( P = 0.05 ) ; the efficacy and safety of the 2- and 3-mg intranasal doses were similar in the youngest cohorts . CONCLUSIONS Results of this phase 1 , pharmacokinetic , and pharmacodynamic study support the potential efficacy of a needle-free glucagon nasal powder delivery system for treatment of hypoglycemia in youth with type 1 diabetes . Given the similar frequency and transient nature of adverse effects of the 2- and 3-mg intranasal doses in the two youngest cohorts , a single 3-mg intranasal dose appears to be appropriate for use across the entire 4- to < 17-year age range We developed an intranasal powder form of glucagon to improve metabolic status and fatty liver in patients with pancreatectomy .  Microcrystalline cellulose , which is commonly used in commercial preparations for allergic rhinitis was used as an absorption enhancer . We compared the intranasal powder form with some spray solutions of glucagon with regard to glucagon absorption , concentration of blood glucose , stability and nasal irritation . The absorption of  glucagon  from the spray solution including 1.5 % sodium glycocholate or 1 % sodium caprate was 1.3- and 2.6-fold higher than that from the powder form mixed with microcrystalline cellulose at a ratio of 1:69 , respectively . The C(max ) values of plasma glucose were 2.18 , 3.39 and 1.56 mmol l(-1 ) in the spray solutions including sodium glycocholate and sodium caprate and in the powder form , respectively . However , glucagon in spray solutions was unstable , but that in the powder form was stable at 5 and 25 degrees C for at least 84 days . The spray solution caused strong irritation , but the powder form did not . These results suggested usefulness of the powder form of glucagon for treatment of pancreatectomized patients Summary The main therapeutic indication for glucagon is the treatment of hypoglycaemia in insulin overdosed Type 1 ( insulin-dependent ) diabetic patients . We have previously shown that an intranasal spray of 7.5 mg glucagon with deoxycholic acid as surfactant was able to correct an i.v . insulin-induced hypoglycaemia in diabetic patients . However , bioavailability and stability needed to be improved before intranasal glucagon could be introduced into clinical practice . This has now been achieved with a freeze-dried mixture of glucagon ( 1 mg ) and glycocholic acid ( 1 mg ) as a surfactant . Kinetics and efficacy have been controlled by ( 1 ) comparing subcutaneous and intranasal glucagon in 12 healthy non-hypoglycaemic subjects ; ( 2 ) testing intranasal glucagon in six Type 1 diabetic patients in whom hypoglycaemia was induced by an i.v . bolus of insulin  and ( 3 ) comparing subcutaneous and intranasal glucagon in six Type 1 diabetic patients in whom hypoglycaemia was induced by adding extra subcutaneous regular insulin to their usual morning dosage . Our results show that 1 mg of intranasal glucagon is as effective as 1 mg of subcutaneous glucagon in terms of the rise in blood glucose . Differences in kinetics between the subcutaneous and the intranasal routes may be observed : intranasal glucagon initiates the blood glucose rise earlier than does the subcutaneous form but the effect of the latter is more sustained . Glycocholic acid appears to be a perfectly tolerated agent in acute conditions . The use of intranasal lyophylized glucagon , for the reversal of hypoglycaemia in Type 1 diabetes , seems to be a clinical ly relevant alternative to its parenteral equivalent and should now be ready to be introduced in the market BACKGROUND Long-term microvascular and neurologic complications cause major morbidity and mortality in patients with insulin-dependent diabetes mellitus ( IDDM ) . We examined whether intensive treatment with the goal of maintaining blood glucose concentrations close to the normal range could decrease the frequency and severity of these complications . METHODS A total of 1441 patients with IDDM--726 with no retinopathy at base line ( the primary -prevention cohort ) and 715 with mild retinopathy ( the secondary -intervention cohort ) were r and omly assigned to intensive therapy administered either with an external insulin pump or by three or more daily insulin injections and guided by frequent blood glucose monitoring or to conventional therapy with one or two daily insulin injections . The patients were followed for a mean of 6.5 years , and the appearance and progression of retinopathy and other complications were assessed regularly . RESULTS In the primary -prevention cohort , intensive therapy reduced the adjusted mean risk for the development of retinopathy by 76 percent ( 95 percent confidence interval , 62 to 85 percent ) , as compared with conventional therapy . In the secondary -intervention cohort , intensive therapy slowed the progression of retinopathy by 54 percent ( 95 percent confidence interval , 39 to 66 percent ) and reduced the development of proliferative or severe nonproliferative retinopathy by 47 percent ( 95 percent confidence interval , 14 to 67 percent ) . In the two cohorts combined , intensive therapy reduced the occurrence of microalbuminuria ( urinary albumin excretion of > or = 40 mg per 24 hours ) by 39 percent ( 95 percent confidence interval , 21 to 52 percent ) , that of albuminuria ( urinary albumin excretion of > or = 300 mg per 24 hours ) by 54 percent ( 95 percent confidence interval 19 to 74 percent ) , and that of clinical neuropathy by 60 percent ( 95 percent confidence interval , 38 to 74 percent ) . The chief adverse event associated with intensive therapy was a two-to-threefold increase in severe hypoglycemia . CONCLUSIONS Intensive therapy effectively delays the onset and slows the progression of diabetic retinopathy , nephropathy , and neuropathy in patients with IDDM To estimate the frequency and morbidity of insulin-induced hypoglycaemia , a retrospective survey was undertaken of the frequency of severe hypoglycaemia in 600 r and omly selected patients with insulin-treated diabetes who were attending a large diabetic outpatient clinic in a teaching hospital . The result ing morbidity ( hypoglycaemia-related injuries , convulsions , and road traffic accidents ) was ascertained in 302 patients . One hundred and seventy-five ( 29.2 % ) of the 600 patients reported a total of 964 episodes of severe hypoglycaemia in the preceding year , giving an overall frequency for the group of 1.60 episodes patient-1year-1 . The frequency of severe hypoglycaemia which was documented in 544 Type 1 ( ketosis prone ) diabetic patients was double that observed in a subgroup of 56 Type 2 diabetic patients who were being treated with insulin ( 1.70 vs 0.73 episodes patient-1year-1 ) . In the subset of 302 patients , those who had experienced severe hypoglycaemia had greater morbidity associated with an estimated rate of injury of 0.04 injuries person-1year-1 . Twenty ( 6.6 % ) patients reported a total of 37 convulsions associated with hypoglycaemia , 5 of which had occurred in the preceding year ( 0.02 convulsions person-1year-1 ) . Five patients reported road traffic accidents in the preceding year which had been caused by hypoglycaemia . The only reliable predictors of severe hypoglycaemia were a history of previous severe hypoglycaemia ( p < 0.001 ) , a history of hypoglycaemia-related injury ( p < 0.001 ) or convulsion ( p < 0.001 ) , and the duration of insulin therapy ( p < 0.001 ) . ( ABSTRACT TRUNCATED AT 250 WORDS Summary The aim of the present study was to compare intranasal glucagon with subcutaneous glucagon as a treatment of insulin-induced hypoglycaemia in 11 children , 7–12 years old , with Type 1 ( insulin-dependent ) diabetes mellitus . Hypoglycaemia ( 1.6±0.1 vs 1.8±0.2 mmol/l ) was induced twice in each child by continuous insulin and variable glucose infusions . One milligram of intranasal glucagon or 0.5 mg of subcutaneous glucagon was given in a r and omized order . At 15 min after the administrations of either intranasal or subcutaneous  glucagon , the blood glucose concentration increased by 1.5±0.2 mmol/l or 1.7±0.2 mmol/l above the glucose nadir , respectively . After nasal administration , the maximal rise in blood glucose was seen after 25 min . Subcutaneous injections induced higher and more sustained plasma glucagon concentrations but the children suffered more often from nausea than when they were treated intranasally . In conclusion , treatment with intranasal glucagon seems to be efficient and results in a rapid correction of insulin-induced hypoglycaemia with few side-effects Intranasal glucagon can raise blood glucose levels in healthy subjects . The aims of this study were to 7 ) compare the hyperglycemic effect of intranasal and intramuscular glucagon in healthy subjects and type I ( insulin-dependent ) diabetes patients during euglycemic conditions and 2 ) test the efficacy of intranasal and intramuscular glucagon in counteracting hypoglycemic episodes in insulin-treated diabetic patients . Intranasal glucagon raised blood glucose levels in both healthy subjects and type I diabetic patients , the effect of intramuscular glucagon being similar for the first 30 min and higher thereafter . Intranasal glucagon was also quicker acting than oral glucose in healthy subjects . Intranasal glucagon raised blood glucose levels in patients with hypoglycemic episodes , although less effectively than intramuscular glucagon . These data indicate intranasal glucagon as a possible emergency remedy for self-medication in insulin-treated patients prone to hypoglycemic episodes OBJECTIVES To develop and vali date a new risk-of-bias tool for nonr and omized studies ( NRSs ) . STUDY DESIGN AND SETTING We developed the Risk of Bias Assessment Tool for Nonr and omized Studies ( RoBANS ) . A validation process with 39 NRSs examined the reliability ( interrater agreement ) , validity ( the degree of correlation between the overall assessment s of RoBANS and Method ological Index for Nonr and omized Studies [ MINORS ] , obtained by plotting the overall risk of bias relative to effect 
    Output:
    
This meta- analysis indicates that in conscious T1DM patients IN glucagon and IM/SC glucagon are equally effective in resolution of hypoglycemia