human
***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 evaluate the efficacy and safety of lixisenatide versus placebo on glycemic control in older patients with type 2 diabetes uncontrolled on their current antidiabetic treatment . RESEARCH DESIGN AND METHODS In this phase III , double-blind , r and omized , placebo-controlled , two-arm , parallel-group , multicenter trial , patients aged ≥70 years were r and omized to receive once-daily lixisenatide 20 μg or placebo before breakfast concomitantly with their existing antidiabetic therapy ( including insulin ) for 24 weeks . Patients at risk for malnutrition or with moderate to severe cognitive impairment were excluded . The primary end point was absolute change in HbA1c from baseline to week 24 . Secondary end points included change from baseline to week 24 in 2-h postpr and ial plasma glucose ( PPG ) and body weight . RESULTS A total of 350 patients were r and omized . HbA1c decreased substantially with lixisenatide ( −0.57 % [ 6.2 mmol/mol ] ) compared with placebo ( + 0.06 % [ 0.7 mmol/mol ] ) from baseline to week 24 ( P < 0.0001 ) . Mean reduction in 2-h PPG was significantly greater with lixisenatide ( −5.12 mmol/L ) than with placebo ( −0.07 mmol/L ; P < 0.0001 ) . A greater decrease in body weight was observed with lixisenatide ( −1.47 kg ) versus placebo ( −0.16 kg ; P < 0.0001 ) . The safety profile of lixisenatide in this older population , including rates of nausea and vomiting , was consistent with that observed in other lixisenatide studies . Hypoglycemia was reported in 17.6 % of patients with lixisenatide versus 10.3 % with placebo . CONCLUSIONS In nonfrail older patients uncontrolled on their current antidiabetic treatment , lixisenatide was superior to placebo in HbA1c reduction and in targeting postpr and ial hyperglycemia , with no unexpected safety findings As life expectancy becomes longer in Japan , there has been an increase of elderly patients with type 2 diabetes who need insulin therapy but can not perform self-injection due to dementia or other conditions . Therefore , the aim of this study was to investigate the efficacy and safety of thrice-weekly insulin degludec therapy in elderly patients with poorly controlled diabetes . The subjects were 22 hospitalized elderly Japanese patients with type 2 diabetes who had difficulty with self-injection . After becoming stable on once-daily insulin degludec treatment , they were assigned to continue once-daily injection ( OD group ) or were switched to thrice-weekly injection ( TW group ) for one week . In the TW group , insulin degludec ( IDeg ) was injected at twice the OD dose before lunch on Monday , Wednesday , and Friday . Glycemic control was assessed by continuous glucose monitoring ( CGM ) over 7 days . The mean 7-day glucose level ( 131±25 mg/dL with OD vs. 152±30 mg/dL with TW , p=0.11 ) and the mean 7-day st and ard deviation ( 32±10 mg/dL with OD vs. 36±14 mg/dL with TW , p=0.45 ) did not differ significantly between the two groups . The percent duration of glucose < 70 mg/dL ( 2.4±3.1 % with OD vs. 1.3±2.5 % with TW , p=0.39 ) and glucose > 200 mg/dL ( 7.2±12.1 % with OD vs. 15.6±18.0 % with TW , p=0.22 ) over 7 days also showed no significant differences between the two groups . In conclusion , thrice-weekly IDeg provided by a visiting nurse could be a practical option for elderly diabetic patients who have difficulty performing self-injection of insulin BACKGROUND The cardiovascular effects of adding once‐weekly treatment with exenatide to usual care in patients with type 2 diabetes are unknown . METHODS We r and omly assigned patients with type 2 diabetes , with or without previous cardiovascular disease , to receive subcutaneous injections of extended‐release exenatide at a dose of 2 mg or matching placebo once weekly . The primary composite outcome was the first occurrence of death from cardiovascular causes , nonfatal myocardial infa rct ion , or nonfatal stroke . The co primary hypotheses were that exenatide , administered once weekly , would be noninferior to placebo with respect to safety and superior to placebo with respect to efficacy . RESULTS In all , 14,752 patients ( of whom 10,782 [ 73.1 % ] had previous cardiovascular disease ) were followed for a median of 3.2 years ( interquartile range , 2.2 to 4.4 ) . A primary composite outcome event occurred in 839 of 7356 patients ( 11.4 % ; 3.7 events per 100 person‐years ) in the exenatide group and in 905 of 7396 patients ( 12.2 % ; 4.0 events per 100 person‐years ) in the placebo group ( hazard ratio , 0.91 ; 95 % confidence interval [ CI ] , 0.83 to 1.00 ) , with the intention‐to‐treat analysis indicating that exenatide , administered once weekly , was noninferior to placebo with respect to safety ( P<0.001 for noninferiority ) but was not superior to placebo with respect to efficacy ( P=0.06 for superiority ) . The rates of death from cardiovascular causes , fatal or nonfatal myocardial infa rct ion , fatal or nonfatal stroke , hospitalization for heart failure , and hospitalization for acute coronary syndrome , and the incidence of acute pancreatitis , pancreatic cancer , medullary thyroid carcinoma , and serious adverse events did not differ significantly between the two groups . CONCLUSIONS Among patients with type 2 diabetes with or without previous cardiovascular disease , the incidence of major adverse cardiovascular events did not differ significantly between patients who received exenatide and those who received placebo . ( Funded by Amylin Pharmaceuticals ; EXSCEL Clinical Trials.gov number , NCT01144338 . Background Mobile health apps for diabetes self-management have different functions . However , the efficacy and safety of each function are not well studied , and no classification is available for these functions . Objective The aims of this study were to ( 1 ) develop and vali date a taxonomy of apps for diabetes self-management , ( 2 ) investigate the glycemic efficacy of  mobile app-based interventions among adults with diabetes in a systematic review of r and omized controlled trials ( RCTs ) , and ( 3 ) explore the contribution of different function to the effectiveness of entire app-based interventions using the taxonomy . Methods We developed a 3-axis taxonomy with columns of clinical modules , rows of functional modules and cells of functions with risk assessment s. This taxonomy was vali date d by review ing and classifying commercially available diabetes apps . We search ed MEDLINE , EMBASE , the Cochrane Central Register of Controlled Trials , the Chinese Biomedical Literature Data base , and Clinical Trials.gov from January 2007 to May 2016 . We included RCTs of adult out patients with diabetes that compared using  mobile app-based interventions with usual care alone . The mean differences ( MDs ) in hemoglobin A1c ( HbA1c ) concentrations and risk ratios of adverse events were pooled using a r and om-effects meta- analysis . After taxonomic classification , we performed exploratory subgroup analyses of the presence or absence of each module across the included app-based interventions . Results Across 12 included trials involving 974 participants , using app-based interventions was associated with a clinical ly significant reduction of HbA1c ( MD 0.48 % , 95 % CI 0.19%-0.78 % ) without excess adverse events . Larger HbA1c reductions were noted among patients with type 2 diabetes than those with type 1 diabetes ( MD 0.67 % , 95 % CI 0.30%-1.03 % vs MD 0.37 % , 95 % CI –0.12%-0.86 % ) . Having a complication prevention module in app-based interventions was associated with a greater HbA1c reduction ( with complication prevention : MD 1.31 % , 95 % CI 0.66%-1.96 % vs without : MD 0.38 % , 95 % CI 0.09%-0.67 % ; intersubgroup P=.01 ) , as was having a structured display ( with structured display : MD 0.69 % , 95 % CI 0.32%-1.06 % vs without : MD 0.69 % , 95 % CI –0.18%-0.53 % ; intersubgroup P=.03 ) . However , having a clinical decision-making function was not associated with a larger HbA1c reduction ( with clinical decision making : MD 0.19 % , 95 % CI –0.24%-0.63 % vs without : MD 0.61 % , 95 % CI 0.27%-0.95 % ; intersubgroup P=.14 ) . Conclusions The use of mobile app-based interventions yields a clinical ly significant HbA1c reduction among adult out patients with diabetes , especially among those with type 2 diabetes . Our study suggests that the clinical decision-making function needs further improvement and evaluation before being added to apps Background : Canagliflozin is a sodium glucose cotransporter 2 inhibitor that reduces the risk of cardiovascular events . We report the effects on heart failure ( HF ) and cardiovascular death overall , in those with and without a baseline history of HF , and in other participant subgroups . Methods : The CANVAS Program ( Canagliflozin Cardiovascular Assessment Study ) enrolled 10 142 participants with type 2 diabetes mellitus and high cardiovascular risk . Participants were r and omly assigned to canagliflozin or placebo and followed for a mean of 188 weeks . The primary end point for these analyses was adjudicated cardiovascular death or hospitalized HF . Results : Participants with a history of HF at baseline ( 14.4 % ) were more frequently women , white , and hypertensive and had a history of prior cardiovascular disease  ( all P<0.001 ) . Greater proportions of these patients were using therapies such as blockers of the renin angiotensin aldosterone system , diuretics , and & bgr;-blockers at baseline ( all P<0.001 ) . Overall , cardiovascular death or hospitalized HF was reduced in those treated with canagliflozin compared with placebo ( 16.3 versus 20.8 per 1000 patient-years ; hazard ratio [ HR ] , 0.78 ; 95 % confidence interval [ CI ] , 0.67–0.91 ) , as was fatal or hospitalized HF ( HR , 0.70 ; 95 % CI , 0.55–0.89 ) and hospitalized HF alone ( HR , 0.67 ; 95 % CI , 0.52–0.87 ) . The benefit on cardiovascular death or hospitalized HF may be greater in patients with a prior history of HF ( HR , 0.61 ; 95 % CI , 0.46–0.80 ) compared with those without HF at baseline ( HR , 0.87 ; 95 % CI , 0.72–1.06 ; P interaction = 0.021 ) . The effects of canagliflozin compared with placebo on other cardiovascular outcomes and key safety outcomes were similar in participants with and without HF at baseline ( all interaction P values > 0.130 ) , except for a possibly reduced absolute rate of events attributable to osmotic diuresis among those with a prior history of HF ( P=0.03 ) . Conclusions : In patients with type 2 diabetes mellitus and an elevated risk of cardiovascular disease , canagliflozin reduced the risk of cardiovascular death or hospitalized HF across a broad range of different patient subgroups . Benefits may be greater in those with a history of HF at baseline . Clinical Trial Registration : URL : https://www . clinical trials.gov . Unique identifiers : NCT01032629 and NCT01989754 ABSTRACT Review of : Neal B , Perkovic V , Mahaffey K , et al. Canagliflozin and cardiovascular and renal events in type 2 diabetes . N Engl J Med . 2017;377:644–657 . The report combines the data from two trials , CANVAS and CANVAS-Renal , which were design ed to evaluate the safety and effect of canagliflozin , an SGLT-2 inhibitor , on the appearance of cardiovascular and renal events in patients with type 2 diabetes . Enrollees were patients with type 2 diabetes of at least 30 years of age , with a glyc 
    Output:
    
agent
Telemedicine interventions can improve communication and connection between older patients and their providers , and improve glycemic control .
Summary A systematic review confirmed the efficacy and safety of metformin as first-line therapy of type 2 diabetes in the older adult , but multiple reports highlighted the risk for vitamin B12 deficiency .
R and omized controlled trials showed the efficacy and safety of antihyperglycemic agents in the elderly , including some with longer duration and lesser risk for hypoglycemia .
R and omized clinical trials showed cardiovascular protection with SGLT-2i ( empagliflozin , canagliflozin ) and GLP-1RA ( liraglutide , semaglutide ) .
***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 evaluate the efficacy and safety of lixisenatide versus placebo on glycemic control in older patients with type 2 diabetes uncontrolled on their current antidiabetic treatment . RESEARCH DESIGN AND METHODS In this phase III , double-blind , r and omized , placebo-controlled , two-arm , parallel-group , multicenter trial , patients aged ≥70 years were r and omized to receive once-daily lixisenatide 20 μg or placebo before breakfast concomitantly with their existing antidiabetic therapy ( including insulin ) for 24 weeks . Patients at risk for malnutrition or with moderate to severe cognitive impairment were excluded . The primary end point was absolute change in HbA1c from baseline to week 24 . Secondary end points included change from baseline to week 24 in 2-h postpr and ial plasma glucose ( PPG ) and body weight . RESULTS A total of 350 patients were r and omized . HbA1c decreased substantially with lixisenatide ( −0.57 % [ 6.2 mmol/mol ] ) compared with placebo ( + 0.06 % [ 0.7 mmol/mol ] ) from baseline to week 24 ( P < 0.0001 ) . Mean reduction in 2-h PPG was significantly greater with lixisenatide ( −5.12 mmol/L ) than with placebo ( −0.07 mmol/L ; P < 0.0001 ) . A greater decrease in body weight was observed with lixisenatide ( −1.47 kg ) versus placebo ( −0.16 kg ; P < 0.0001 ) . The safety profile of lixisenatide in this older population , including rates of nausea and vomiting , was consistent with that observed in other lixisenatide studies . Hypoglycemia was reported in 17.6 % of patients with lixisenatide versus 10.3 % with placebo . CONCLUSIONS In nonfrail older patients uncontrolled on their current antidiabetic treatment , lixisenatide was superior to placebo in HbA1c reduction and in targeting postpr and ial hyperglycemia , with no unexpected safety findings As life expectancy becomes longer in Japan , there has been an increase of elderly patients with type 2 diabetes who need insulin therapy but can not perform self-injection due to dementia or other conditions . Therefore , the aim of this study was to investigate the efficacy and safety of thrice-weekly insulin degludec therapy in elderly patients with poorly controlled diabetes . The subjects were 22 hospitalized elderly Japanese patients with type 2 diabetes who had difficulty with self-injection . After becoming stable on once-daily insulin degludec treatment , they were assigned to continue once-daily injection ( OD group ) or were switched to thrice-weekly injection ( TW group ) for one week . In the TW group , insulin degludec ( IDeg ) was injected at twice the OD dose before lunch on Monday , Wednesday , and Friday . Glycemic control was assessed by continuous glucose monitoring ( CGM ) over 7 days . The mean 7-day glucose level ( 131±25 mg/dL with OD vs. 152±30 mg/dL with TW , p=0.11 ) and the mean 7-day st and ard deviation ( 32±10 mg/dL with OD vs. 36±14 mg/dL with TW , p=0.45 ) did not differ significantly between the two groups . The percent duration of glucose < 70 mg/dL ( 2.4±3.1 % with OD vs. 1.3±2.5 % with TW , p=0.39 ) and glucose > 200 mg/dL ( 7.2±12.1 % with OD vs. 15.6±18.0 % with TW , p=0.22 ) over 7 days also showed no significant differences between the two groups . In conclusion , thrice-weekly IDeg provided by a visiting nurse could be a practical option for elderly diabetic patients who have difficulty performing self-injection of insulin BACKGROUND The cardiovascular effects of adding once‐weekly treatment with exenatide to usual care in patients with type 2 diabetes are unknown . METHODS We r and omly assigned patients with type 2 diabetes , with or without previous cardiovascular disease , to receive subcutaneous injections of extended‐release exenatide at a dose of 2 mg or matching placebo once weekly . The primary composite outcome was the first occurrence of death from cardiovascular causes , nonfatal myocardial infa rct ion , or nonfatal stroke . The co primary hypotheses were that exenatide , administered once weekly , would be noninferior to placebo with respect to safety and superior to placebo with respect to efficacy . RESULTS In all , 14,752 patients ( of whom 10,782 [ 73.1 % ] had previous cardiovascular disease ) were followed for a median of 3.2 years ( interquartile range , 2.2 to 4.4 ) . A primary composite outcome event occurred in 839 of 7356 patients ( 11.4 % ; 3.7 events per 100 person‐years ) in the exenatide group and in 905 of 7396 patients ( 12.2 % ; 4.0 events per 100 person‐years ) in the placebo group ( hazard ratio , 0.91 ; 95 % confidence interval [ CI ] , 0.83 to 1.00 ) , with the intention‐to‐treat analysis indicating that exenatide , administered once weekly , was noninferior to placebo with respect to safety ( P<0.001 for noninferiority ) but was not superior to placebo with respect to efficacy ( P=0.06 for superiority ) . The rates of death from cardiovascular causes , fatal or nonfatal myocardial infa rct ion , fatal or nonfatal stroke , hospitalization for heart failure , and hospitalization for acute coronary syndrome , and the incidence of acute pancreatitis , pancreatic cancer , medullary thyroid carcinoma , and serious adverse events did not differ significantly between the two groups . CONCLUSIONS Among patients with type 2 diabetes with or without previous cardiovascular disease , the incidence of major adverse cardiovascular events did not differ significantly between patients who received exenatide and those who received placebo . ( Funded by Amylin Pharmaceuticals ; EXSCEL Clinical Trials.gov number , NCT01144338 . Background Mobile health apps for diabetes self-management have different functions . However , the efficacy and safety of each function are not well studied , and no classification is available for these functions . Objective The aims of this study were to ( 1 ) develop and vali date a taxonomy of apps for diabetes self-management , ( 2 ) investigate the glycemic efficacy of  mobile app-based interventions among adults with diabetes in a systematic review of r and omized controlled trials ( RCTs ) , and ( 3 ) explore the contribution of different function to the effectiveness of entire app-based interventions using the taxonomy . Methods We developed a 3-axis taxonomy with columns of clinical modules , rows of functional modules and cells of functions with risk assessment s. This taxonomy was vali date d by review ing and classifying commercially available diabetes apps . We search ed MEDLINE , EMBASE , the Cochrane Central Register of Controlled Trials , the Chinese Biomedical Literature Data base , and Clinical Trials.gov from January 2007 to May 2016 . We included RCTs of adult out patients with diabetes that compared using  mobile app-based interventions with usual care alone . The mean differences ( MDs ) in hemoglobin A1c ( HbA1c ) concentrations and risk ratios of adverse events were pooled using a r and om-effects meta- analysis . After taxonomic classification , we performed exploratory subgroup analyses of the presence or absence of each module across the included app-based interventions . Results Across 12 included trials involving 974 participants , using app-based interventions was associated with a clinical ly significant reduction of HbA1c ( MD 0.48 % , 95 % CI 0.19%-0.78 % ) without excess adverse events . Larger HbA1c reductions were noted among patients with type 2 diabetes than those with type 1 diabetes ( MD 0.67 % , 95 % CI 0.30%-1.03 % vs MD 0.37 % , 95 % CI –0.12%-0.86 % ) . Having a complication prevention module in app-based interventions was associated with a greater HbA1c reduction ( with complication prevention : MD 1.31 % , 95 % CI 0.66%-1.96 % vs without : MD 0.38 % , 95 % CI 0.09%-0.67 % ; intersubgroup P=.01 ) , as was having a structured display ( with structured display : MD 0.69 % , 95 % CI 0.32%-1.06 % vs without : MD 0.69 % , 95 % CI –0.18%-0.53 % ; intersubgroup P=.03 ) . However , having a clinical decision-making function was not associated with a larger HbA1c reduction ( with clinical decision making : MD 0.19 % , 95 % CI –0.24%-0.63 % vs without : MD 0.61 % , 95 % CI 0.27%-0.95 % ; intersubgroup P=.14 ) . Conclusions The use of mobile app-based interventions yields a clinical ly significant HbA1c reduction among adult out patients with diabetes , especially among those with type 2 diabetes . Our study suggests that the clinical decision-making function needs further improvement and evaluation before being added to apps Background : Canagliflozin is a sodium glucose cotransporter 2 inhibitor that reduces the risk of cardiovascular events . We report the effects on heart failure ( HF ) and cardiovascular death overall , in those with and without a baseline history of HF , and in other participant subgroups . Methods : The CANVAS Program ( Canagliflozin Cardiovascular Assessment Study ) enrolled 10 142 participants with type 2 diabetes mellitus and high cardiovascular risk . Participants were r and omly assigned to canagliflozin or placebo and followed for a mean of 188 weeks . The primary end point for these analyses was adjudicated cardiovascular death or hospitalized HF . Results : Participants with a history of HF at baseline ( 14.4 % ) were more frequently women , white , and hypertensive and had a history of prior cardiovascular disease  ( all P<0.001 ) . Greater proportions of these patients were using therapies such as blockers of the renin angiotensin aldosterone system , diuretics , and & bgr;-blockers at baseline ( all P<0.001 ) . Overall , cardiovascular death or hospitalized HF was reduced in those treated with canagliflozin compared with placebo ( 16.3 versus 20.8 per 1000 patient-years ; hazard ratio [ HR ] , 0.78 ; 95 % confidence interval [ CI ] , 0.67–0.91 ) , as was fatal or hospitalized HF ( HR , 0.70 ; 95 % CI , 0.55–0.89 ) and hospitalized HF alone ( HR , 0.67 ; 95 % CI , 0.52–0.87 ) . The benefit on cardiovascular death or hospitalized HF may be greater in patients with a prior history of HF ( HR , 0.61 ; 95 % CI , 0.46–0.80 ) compared with those without HF at baseline ( HR , 0.87 ; 95 % CI , 0.72–1.06 ; P interaction = 0.021 ) . The effects of canagliflozin compared with placebo on other cardiovascular outcomes and key safety outcomes were similar in participants with and without HF at baseline ( all interaction P values > 0.130 ) , except for a possibly reduced absolute rate of events attributable to osmotic diuresis among those with a prior history of HF ( P=0.03 ) . Conclusions : In patients with type 2 diabetes mellitus and an elevated risk of cardiovascular disease , canagliflozin reduced the risk of cardiovascular death or hospitalized HF across a broad range of different patient subgroups . Benefits may be greater in those with a history of HF at baseline . Clinical Trial Registration : URL : https://www . clinical trials.gov . Unique identifiers : NCT01032629 and NCT01989754 ABSTRACT Review of : Neal B , Perkovic V , Mahaffey K , et al. Canagliflozin and cardiovascular and renal events in type 2 diabetes . N Engl J Med . 2017;377:644–657 . The report combines the data from two trials , CANVAS and CANVAS-Renal , which were design ed to evaluate the safety and effect of canagliflozin , an SGLT-2 inhibitor , on the appearance of cardiovascular and renal events in patients with type 2 diabetes . Enrollees were patients with type 2 diabetes of at least 30 years of age , with a glyc 
    Output:
    