Treatment patterns in patients with type 2 diabetes mellitus treated with glucagon-like peptide-1 receptor agonists: Higher adherence and persistence with dulaglutide compared with once-weekly exenatide and liraglutide.

To compare adherence (proportion of days covered [PDC]), persistence, and treatment patterns among patients with type 2 diabetes mellitus (T2DM) newly initiating glucagon-like peptide-1 receptor agonists (GLP-1RAs). More specifically, the main objectives were to compare dulaglutide vs exenatide once weekly and dulaglutide vs liraglutide. Patients with T2DM newly initiating dulaglutide, albiglutide, exenatide once weekly, exenatide twice daily and liraglutide between November 2014 and April 2015 were hierarchically selected from Truven Health's MarketScan Research Databases. Propensity score matching was used to account for selection bias. Adherence to and persistence with the index GLP-1RA, and switching and augmentation patterns were assessed during the 6-month post-index period. Mean adherence for the matched cohorts was significantly higher for dulaglutide than for exenatide once weekly (0.72 vs 0.61; P  < .0001) and liraglutide (0.71 vs 0.67; P  < .0001). The percentage of patients achieving PDC ≥ 0.80 was significantly higher for dulaglutide compared with exenatide once weekly (54.2% vs 37.9%; P  < .0001) and liraglutide (53.5% vs 44.3%; P  < .0001). The mean (standard deviation) days on treatment for all matched patients was significantly higher for patients in the dulaglutide cohort compared with those in the exenatide once-weekly (148.4 [55.4] vs 123.6 [61.6]; P  < .0001) and liraglutide cohorts (146.0 [56.9] vs 137.4 [60.1]; P  < .0001). A significantly lower proportion of patients on dulaglutide discontinued treatment compared with those on exenatide once weekly (26.2% vs 48.4%; P  < .0001) and those on liraglutide (28.0% vs 35.6%; P  < .0001). Dulaglutide initiators had significantly higher adherence, were more persistent, and had lower discontinuation rates compared with initiators of exenatide once weekly or liraglutide during the 6-month follow-up period.

Alatorre C ，Fernández Landó L ，Yu M ，Brown K ，Montejano L ，Juneau P ，Mody R ，Swindle R ... -  《-》

Efficacy and safety of glucagon-like peptide-1 receptor agonists in type 2 diabetes: A systematic review and mixed-treatment comparison analysis.

To compare efficacy and safety of glucagon-like peptide-1 receptor agonists (GLP-1RAs) in people with type 2 diabetes. We electronically searched, up to June 3, 2016, published randomized clinical trials lasting between 24 and 32 weeks that compared a GLP-1RA (albiglutide, dulaglutide, twice-daily exenatide and once-weekly exenatide, liraglutide, lixisenatide, semaglutide and taspoglutide) with placebo or another GLP-1RA. Data on cardiometabolic and safety outcomes were analysed using a mixed-treatment comparison meta-analysis. A total of 34 trials (14 464 participants) met the inclusion criteria; no published data for semaglutide were available. Compared with placebo, all GLP-1RAs reduced glycated haemoglobin (HbA1c) and fasting plasma glucose (FPG) levels (reductions ranged from -0.55% and -0.73 mmol/L, respectively, for lixisenatide to -1.21% and -1.97 mmol/L, respectively, for dulaglutide). There were no differences within short-acting (twice-daily exenatide and lixisenatide) or long-acting (albiglutide, dulaglutide, once-weekly exenatide, liraglutide and taspoglutide) groups. Compared with twice-daily exenatide, dulaglutide treatment was associated with the greatest HbA1c and FPG reduction (0.51% and 1.04 mmol/L, respectively), followed by liraglutide (0.45% and 0.93 mmol/L, respectively) and once-weekly exenatide (0.38% and 0.85 mmol/L, respectively); similar reductions were found when these 3 agents were compared with lixisenatide. Compared with placebo, all GLP-1RAs except albiglutide reduced weight and increased the risk of hypoglycaemia and gastrointestinal side effects, and all agents except dulaglutide and taspoglutide reduced systolic blood pressure. When all GLP-1RAs were compared with each other, no clinically meaningful differences were observed in weight loss, blood pressure reduction or hypoglycaemia risk. Albiglutide had the lowest risk of nausea and diarrhoea and once-weekly exenatide the lowest risk of vomiting. The RCTs in the present analysis show that all GLP-1RAs improve glycaemic control, reduce body weight and increase the risk of adverse gastrointestinal symptoms compared with placebo. Although there were no differences when short-acting agents were compared with each other or when long-acting agents were compared with each other, dulaglutide, liraglutide and once-weekly exenatide were superior to twice-daily exenatide and lixisenatide at lowering HbA1c and FPG levels. There were no differences in hypoglycaemia between these 3 agents, whilst once-weekly exenatide had the lowest risk of vomiting. These results, along with patient's preferences and individualized targets, should be considered when selecting a GLP-1RA.

Htike ZZ ，Zaccardi F ，Papamargaritis D ，Webb DR ，Khunti K ，Davies MJ ... -  《-》

Adherence, persistence, glycaemic control and costs among patients with type 2 diabetes initiating dulaglutide compared with liraglutide or exenatide once weekly at 12-month follow-up in a real-world setting in the United States.

To evaluate adherence, persistence, glycaemic control and costs at 12-month follow-up for patients initiating dulaglutide versus liraglutide or exenatide once weekly. The present retrospective observational claims study included patients with type 2 diabetes (T2D) and ≥ 1 pharmacy claim for dulaglutide, liraglutide or exenatide once weekly from the HealthCore Integrated Research Database. Adherence was defined as proportion of days covered ≥80%, and persistence was measured by time to discontinuation of index therapy. Change from baseline in glycated haemoglobin (HbA1c) concentration was assessed in a subset with pre- and post-index HbA1c results. Propensity scores were used to match the cohorts. The baseline characteristics were balanced for the matched cohorts, dulaglutide versus liraglutide (n = 2471) and dulaglutide versus exenatide once weekly (n = 1891). Among those initiating dulaglutide there was a significantly higher proportion of adherent patients compared with the groups initiating liraglutide (51.2% vs. 38.2%; P < 0.001) and exenatide once weekly (50.7% vs. 31.9%; P < 0.001). At 12 months, 55% of patients in the dulaglutide group versus 43.8% in the liraglutide group (P < 0.001), and 54.9% in the dulaglutide versus 34.4% in the exenatide once-weekly group (P < 0.001) were persistent. The dulaglutide group had a significantly greater reduction in HbA1c than the liraglutide group (-34.24 vs. -31.94 mmol/mol; P = 0.032), and a greater, but nonsignificant, reduction in HbA1c than the exenatide once-weekly group (-34.46 vs. -31.94 mmol/mol; P = 0.056). The diabetes-related total costs were not significantly different between the dulaglutide and the liraglutide group ($16,174 vs. $16,694; P = 0.184), and were significantly higher for dulaglutide than for exenatide once weekly ($15,768 vs. $14,615; P = 0.005). Adherence and persistence are important considerations in patient-centric treatment selection for patients with T2D. Higher adherence and persistence for dulaglutide compared with liraglutide or exenatide once weekly are relevant criteria when choosing glucagon-like peptide-1 receptor agonist treatment for patients with T2D.

Mody R ，Huang Q ，Yu M ，Zhao R ，Patel H ，Grabner M ，Landó LF ... -  《-》

Efficacy and safety of once-weekly glucagon-like peptide-1 receptor agonists compared with exenatide and liraglutide in type 2 diabetes: a systemic review of randomised controlled trials.

Once-weekly glucagon-like peptide-1 receptor agonists (GLP-1RAs) have shown promising results in the treatment of type 2 diabetes. Herein, we compared the efficacy and safety of once-weekly GLP-1RAs with exenatide and liraglutide separately. We systematically surveyed the pertinent literature using various databases. The randomised controlled trials that compared once-weekly GLP-1RAs with exenatide and liraglutide in type 2 diabetes were included. Our main end-points were control of glycaemia, body weight, hypoglycaemia and gastrointestinal adverse events (AEs). Our analysis included eight trials involving 5531 patients. Exenatide-long-acting release (LAR), dulaglutide and taspoglutide were more effective than twice-daily exenatide in reducing glycosylated haemoglobin A1c (HbA1c) and fasting blood glucose (FBG) levels and achieving HbA1c targets (< 7.0% and ≤ 6.5%). Liraglutide was as effective as dulaglutide and more effective than exenatide-LAR and albiglutide in controlling glycaemia. With regard to the effectiveness in decreasing body weight, exenatide-LAR, dulaglutide and taspoglutide were similar to exenatide whereas exenatide-LAR, dulaglutide and albiglutide were inferior to liraglutide. Once-weekly GLP-1RAs, exenatide and liraglutide resulted in a similar incidence of hypoglycaemia and of gastrointestinal, serious, or other AEs. Once-weekly GLP-1RAs were more effective in controlling glycaemia and equally effective in decreasing body weight than twice-daily exenatide but were inferior to liraglutide in controlling these two parameters (dulaglutide was similar with liraglutide in controlling glycaemia). Once-weekly GLP-1RAs, exenatide and liraglutide had a similar risk of causing AEs.

Xue X ，Ren Z ，Zhang A ，Yang Q ，Zhang W ，Liu F ... -  《-》

Comparative effectiveness of once-weekly glucagon-like peptide-1 receptor agonists with regard to 6-month glycaemic control and weight outcomes in patients with type 2 diabetes.

A retrospective cohort study was conducted in patients with type 2 diabetes in an electronic medical record database to compare real-world, 6-month glycated haemoglobin (HbA1c) and weight outcomes for exenatide once weekly with those for dulaglutide and albiglutide. The study included 2465 patients: exenatide once weekly, n = 2133; dulaglutide, n = 201; and albiglutide, n = 131. The overall mean (standard deviation [s.d.]) age was 60 (11) years and 54% were men; neither differed among the comparison groups. The mean (s.d.) baseline HbA1c was similar in the exenatide once-weekly (8.3 [1.7]%) and dulaglutide groups (8.5 [1.5]%; P = .165), but higher in the albiglutide group (8.7 [1.7]%; P < .001). The overall mean (s.d.) HbA1c change was -0.5 (1.5)% (P < .001) and this did not differ among the comparison groups in either adjusted or unadjusted analyses. The mean (s.d.) weight change was -1.4 (4.7) kg for exenatide once weekly and -1.6 (3.7) kg for albiglutide (P = .579), but was greater for dulaglutide, at -2.7 (5.7) kg (P = .001). Outcomes were similar in subsets of insulin-naive patients with baseline HbA1c ≥7.0% or ≥9.0%. All agents significantly reduced HbA1c at 6 months, with no significant differences among agents or according to baseline HbA1c in insulin-naive subgroups.

Unni S ，Wittbrodt E ，Ma J ，Schauerhamer M ，Hurd J ，Ruiz-Negrón N ，McAdam-Marx C ... -  《-》