***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: Importance Hypoglycemia , common in patients with type 1 diabetes , is a major barrier to achieving good glycemic control . Severe hypoglycemia can lead to coma or death . Objective To determine whether insulin degludec is noninferior or superior to insulin glargine U100 in reducing the rate of symptomatic hypoglycemic episodes . Design , Setting , and Participants Double-blind , r and omized , crossover noninferiority trial involving 501 adults with at least 1 hypoglycemia risk factor treated at 84 US and 6 Polish centers ( January 2014-January 12 , 2016 ) for two 32-week treatment periods , each with a 16-week titration and a 16-week maintenance period . Interventions Patients were r and omized 1:1 to receive once-daily insulin degludec followed by insulin glargine U100 ( n = 249 ) or to receive insulin glargine U100 followed by insulin degludec ( n = 252 ) and r and omized 1:1 to morning or evening dosing within each treatment sequence . Main Outcomes and Measures The primary end point was the rate of overall severe or blood glucose-confirmed ( < 56 mg/dL ) symptomatic hypoglycemic episodes during the maintenance period . Secondary end points included the rate of nocturnal symptomatic hypoglycemic episodes and proportion of patients with severe hypoglycemia during the maintenance period . The noninferiority criterion for the primary end point and for the secondary end point of nocturnal hypoglycemia was defined as an upper limit of the 2-sided 95 % CI for a rate ratio of 1.10 or lower ; if noninferiority was established , 2-sided statistical testing for superiority was conducted . Results Of the 501 patients r and omized ( mean age , 45.9 years ; 53.7 % men ) , 395 ( 78.8 % ) completed the trial . During the maintenance period , the rates of overall symptomatic hypoglycemia were 2200.9 episodes per 100 person-years ’ exposure ( PYE ) in the insulin degludec group vs 2462.7 episodes per 100 PYE in the insulin glargine U100 group for a rate ratio ( RR ) of 0.89 ( 95 % CI , 0.85 - 0.94 ; P < .001 for noninferiority ; P < .001 for superiority ; rate difference , −130.31 episodes per 100 PYE ; 95 % CI , −193.5 to −67.16 ) . The rates of nocturnal symptomatic hypoglycemia were 277.1 per 100 PYE in the insulin degludec group vs 428.6 episodes per 100 PYE in the insulin glargine U100 group , for an RR of 0.64 ( 95 % CI , 0.56 - 0.73 ; P < .001 for noninferiority ; P < .001 for superiority ; rate difference , −61.94 episodes per 100 PYE ; 95 % CI , −83.85 to −40.03 ) . A lower proportion of patients in the insulin degludec than in the insulin glargine U100 group experienced severe hypoglycemia during the maintenance period ( 10.3 % , 95 % CI , 7.3%-13.3 % vs 17.1 % , 95 % CI , 13.4%-20.8 % , respectively ; McNemar P = .002 ; risk difference , −6.8 % ; 95 % CI , −10.8 % to −2.7 % ) . Conclusions and Relevance Among patients with type 1 diabetes and at least 1 risk factor for hypoglycemia , 32 weeks ’ treatment with insulin degludec vs insulin glargine U100 result ed in a reduced rate of overall symptomatic hypoglycemic episodes . Trial Registration clinical trials.gov Identifier : Importance Hypoglycemia , a serious risk for insulin-treated patients with type 2 diabetes , negatively affects glycemic control . Objective To test whether treatment with basal insulin degludec is associated with a lower rate of hypoglycemia compared with insulin glargine U100 in patients with type 2 diabetes . Design , Setting , and Participants R and omized , double-blind , treat-to-target crossover trial including two 32-week treatment periods , each with a 16-week titration period and a 16-week maintenance period . The trial was conducted at 152 US centers between January 2014 and December 2015 in 721 adults with type 2 diabetes and at least 1 hypoglycemia risk factor who were previously treated with basal insulin with or without oral antidiabetic drugs . Interventions Patients were r and omized 1:1 to receive once-daily insulin degludec followed by insulin glargine U100 ( n = 361 ) or to receive insulin glargine U100 followed by insulin degludec ( n = 360 ) and r and omized 1:1 to morning or evening dosing within each treatment sequence . Main Outcomes and Measures The primary end point was the rate of overall symptomatic hypoglycemic episodes ( severe or blood glucose confirmed [ < 56 mg/dL ] ) during the maintenance period . Secondary end points were the rate of nocturnal symptomatic hypoglycemic episodes ( severe or blood glucose confirmed , occurring between 12:01 AM and 5:59 AM ) and the proportion of patients with severe hypoglycemia during the maintenance period . Results Of the 721 patients r and omized ( mean [ SD ] age , 61.4 [ 10.5 ] years ; 53.1 % male ) , 580 ( 80.4 % ) completed the trial . During the maintenance period , the rates of overall symptomatic hypoglycemia for insulin degludec vs insulin glargine U100 were 185.6 vs 265.4 episodes per 100 patient-years of exposure ( PYE ) ( rate ratio = 0.70 [ 95 % CI , 0.61 - 0.80 ] ; P < .001 ; difference , −23.66 episodes/100 PYE [ 95 % CI , −33.98 to −13.33 ] ) , and the proportions of patients with hypoglycemic episodes were 22.5 % vs 31.6 % ( difference , −9.1 % [ 95 % CI , −13.1 % to −5.0 % ] ) . The rates of nocturnal symptomatic hypoglycemia with insulin degludec vs insulin glargine U100 were 55.2 vs 93.6 episodes/100 PYE ( rate ratio = 0.58 [ 95 % CI , 0.46 - 0.74 ] ; P < .001 ; difference , −7.41 episodes/100 PYE [ 95 % CI , −11.98 to −2.85 ] ) , and the proportions of patients with hypoglycemic episodes were 9.7 % vs 14.7 % ( difference , −5.1 % [ 95 % CI , −8.1 % to −2.0 % ] ) . The proportions of patients experiencing severe hypoglycemia during the maintenance period were 1.6 % ( 95 % CI , 0.6%-2.7 % ) for insulin degludec vs 2.4 % ( 95 % CI , 1.1%-3.7 % ) for insulin glargine U100 ( McNemar P = .35 ; risk difference , −0.8 % [ 95 % CI , −2.2 % to 0.5 % ] ) . Statistically significant reductions in overall and nocturnal symptomatic hypoglycemia for insulin degludec vs insulin glargine U100 were also seen for the full treatment period . Conclusions and Relevance Among patients with type 2 diabetes treated with insulin and with at least 1 hypoglycemia risk factor , 32 weeks ’ treatment with insulin degludec vs insulin glargine U100 result ed in a reduced rate of overall symptomatic hypoglycemia . Trial Registration clinical trials.gov Identifier : BACKGROUND Glucagon-like peptide-1 ( GLP-1 ) receptor agonists and sodium-glucose co-transporter-2 ( SGLT2 ) inhibitors improve glycaemic control and reduce bodyweight in patients with type 2 diabetes through different mechanisms . We assessed the safety and efficacy of the addition of the once-weekly GLP-1 receptor agonist dulaglutide to the ongoing treatment regimen in patients whose diabetes is inadequately controlled with SGLT2 inhibitors , with or without metformin .  METHODS AWARD-10 was a phase 3b , double-blind , parallel-arm , placebo-controlled , 24-week study done at 40 clinical sites in Austria , Czech Republic , Germany , Hungary , Israel , Mexico , Spain , and the USA . Eligible adult patients ( ≥18 years ) with inadequately controlled type 2 diabetes ( HbA1c concentration ≥7·0 % [ 53 mmol/mol ] and ≤9·5 % [ 80 mmol/mol ] ) , a BMI of 45 kg/m2 or less , and taking stable doses ( > 3 months ) of an SGLT2 inhibitor ( with or without metformin )  were r and omly assigned ( 1:1:1 ) via an interactive web-response system to subcutaneous injections of either dulaglutide 1·5 mg , dulaglutide 0·75 mg , or placebo once per week for 24 weeks . Patients and investigators were masked to dulaglutide and placebo assignment , and those assessing outcomes were masked to study drug assignment . The primary objective was to test for the superiority of dulaglutide ( 1·5 mg or 0·75 mg ) versus placebo for change in HbA1c concentration from baseline at 24 weeks . All analyses were done in the intention-to-treat population , defined as all r and omly assigned patients who received at least one dose of study drug . This study is registered with Clinical Trials.gov , number NCT02597049 . FINDINGS Between Dec 7 , 2015 , and Feb 3 , 2017 , 424 patients were r and omly assigned to dulaglutide 1·5 mg ( n=142 ) , dulaglutide 0·75 mg ( n=142 ) , and placebo ( n=140 ) . One patient in the dulaglutide 0·75 mg group was excluded from the analysis because they did not receive any dose of the study drug . The reduction in HbA1c concentration at 24 weeks was larger in patients receiving dulaglutide ( least squares mean [ LSM ] for dulaglutide 1·5 mg -1·34 % [ SE 0·06 ] or -14·7 mmol/mol [ 0·6 ] ; dulaglutide 0·75 mg -1·21 % [ 0·06 ] or -13·2 mmol/mol [ 0·6 ] ) than in patients receiving placebo ( -0·54 % [ 0·06 ] or -5·9 mmol/mol [ 0·6 ] ; p<0·0001 for both groups vs placebo ) . The LSM differences were -0·79 % ( 95 % CI -0·97 to -0·61 ) or -8·6 mmol/mol ( -10·6 to -6·7 ) for dulaglutide 1·5 mg and -0·66 % ( -0·84 to -0·49 ) or -7·2 mmol/mol ( -9·2 to -5·4 ) for dulaglutide 0·75 mg ( p<0·0001 for both ) . Serious adverse events were reported for five ( 4 % ) patients in the dulaglutide 1·5 mg group , three ( 2 % ) patients in the dulaglutide 0·75 mg group , and five ( 4 % ) patients in the placebo group . Treatment-emergent adverse events were more common in patients treated with dulaglutide than in patients who received placebo , mainly because of an increased incidence of gastrointestinal adverse events . Nausea ( 21 [ 15 % ] patients in the dulaglutide 1·5 mg group vs seven [ 5 % ] in the dulaglutide 0·75 mg group vs five [ 4 % ] in the placebo group ) , diarrhoea ( eight [ 6 % ] vs 14 [ 10 % ] vs four [ 3 % ] ) , and vomiting ( five [ 4 % ] vs four [ 3 % ] vs one [ 1 % ] ) were more common with dulaglutide than with placebo . One episode of severe hypoglycaemia was reported in the dulaglutide 0·75 mg group . Two ( 1 % ) patients receiving dulaglutide 1·5 mg died , but these deaths were not considered to be related to study drug ; no deaths 
    Output:
    
Reductions in total and LDL cholesterol were found .
The present review supports treatment intensification with GLP-1RA in uncontrolled type 2 diabetes on SGLT2i .
This drug regimen could provide improved HbA1c control , together with enhanced weight loss and blood pressure and lipids control