IDegLira is Efficacious Across Baseline HbA1C Categories in Subjects with Type 2 Diabetes Uncontrolled on SU, GLP-1RA or Insulin Glargine: Analyses from Completed Phase 3b Trials

AimsTo assess efficacy and safety of dulaglutide 1.5 mg combined with insulin, categorized by subgroups of baseline glycated haemoglobin (HbA1c; ≤9% and >9% [≤74.9 and >74.9 mmol/mol]), age (<65 and ≥65 years), and duration of diabetes (<10 and ≥10 years) at 6 months in patients with type 2 diabetes (T2D).Materials and methodsThis pooled analysis was conducted in a population of patients with T2D with similar baseline characteristics who were included in the AWARD‐4 and AWARD‐9 clinical trials and randomized to dulaglutide 1.5 mg (pooled mean baseline age 59 years, duration of diabetes 13 years, HbA1c 8.4% [68.3 mmol/mol]). Weight and hypoglycaemia were analysed by individual trial. In AWARD‐4, dulaglutide plus lispro three times daily was assessed against glargine plus lispro three times daily. In AWARD‐9, dulaglutide added to glargine was assessed against placebo added to glargine. Insulins were titrated to target in both trials.ResultsA total of 445 patients were included in this analysis (73% with HbA1c ≤9%, 27% [≤74.9 mmol/mol] with HbA1c >9% [>74.9 mmol/mol]; 70% aged <65 years, 30% aged ≥65 years; 36% with duration of diabetes <10 years, 64% with duration of diabetes ≥10 years). At 6 months, dulaglutide 1.5 mg significantly reduced HbA1c in all subgroups (P < .001), with the highest reduction observed in patients with baseline HbA1c >9% (>74.9 mmol/mol) (range − 1.3% to −2.5% [−14.2 to −27.3 mmol/mol]). The incidence rates of documented symptomatic and severe hypoglycaemia were similar in all subgroups in both trials. The most common adverse events observed in each trial were gastrointestinal in nature.ConclusionDulaglutide 1.5 mg combined with basal or prandial insulin is efficacious for patients with T2D irrespective of age, duration of diabetes or baseline HbA1c.

Section: Discussionsupporting

confidence: 84%

Dulaglutide 1.5 mg as an add‐on option for patients uncontrolled on insulin: Subgroup analysis by age, duration of diabetes and baseline glycated haemoglobin concentration

Pantalone

Patel

et al. 2018

“…Similar results have also been obtained with IDegLira, a fixed‐ratio combination of insulin degludec and the long‐acting GLP‐1RA liraglutide when analysing subgroups of patients with baseline HbA1c and BMI, including a post hoc analysis of the DUAL I extension and DUAL II trials …”

Section: Discussionsupporting

confidence: 71%

“…The ability to show that a treatment strategy is more or less equally effective according to the initial characteristics of the patients can be of benefit to clinicians and patients. Furthermore, understanding the underlying factors that may influence response to new treatment options such as iGlarLixi, may be of particular value . The objective of the present exploratory subpopulation analysis was to examine the efficacy in subpopulations of patients based on baseline glycated haemoglobin (HbA1c), disease duration and body mass index (BMI) in the LixiLan‐O trial.…”

Section: Introductionmentioning

confidence: 99%

Impact of baseline glycated haemoglobin, diabetes duration and body mass index on clinical outcomes in the LixiLan‐O trial testing a titratable fixed‐ratio combination of insulin glargine/lixisenatide (iGlarLixi) vs insulin glargine and lixisenatide monocomponents

Davies

Leiter

Guerci

et al. 2017

To determine whether baseline characteristics had an impact on clinical outcomes in the LixiLan‐O trial (N = 1170), we compared the efficacy and safety of iGlarLixi, a titratable fixed‐ratio combination of insulin glargine 100 U (iGlar) and lixisenatide (Lixi) with iGlar or Lixi alone in patients with uncontrolled type 2 diabetes mellitus (T2DM) on oral therapy. Subgroups according to baseline glycated haemoglobin (HbA1c; <8% or ≥8% [<64 or ≥64 mmol/mol]), T2DM disease duration (<7 or ≥7 years) and body mass index (BMI; <30 or ≥30 kg/m2) were investigated. In all subpopulations, iGlarLixi was consistently statistically superior to iGlar and Lixi alone in reducing HbA1c from baseline to week 30; higher proportions of patients achieved HbA1c <7% (<53 mmol/mol) with iGlarLixi vs iGlar and Lixi alone. Compared with iGlar, iGlarLixi resulted in a substantial decrease in 2‐hour postprandial plasma glucose levels, and mitigation of weight gain, with no differences among subpopulations in incidence of symptomatic hypoglycaemia. iGlarLixi consistently improved glycaemic control compared with iGlar and Lixi alone, without weight gain or increase in hypoglycaemic risk compared with iGlar in the subpopulations tested, regardless of baseline HbA1c, disease duration and BMI.

“…The hypoglycaemia results, therefore, were also analysed by dosing time, and by varying the definition of the nocturnal period to better characterize the clinical profile of IDegLira with regard to its relative risks for hypoglycaemia. In addition, previous analyses have shown that IDegLira is efficacious regardless of baseline characteristics, such as BMI and glycated haemoglobin (HbA1c) . In the present analysis, we assessed whether the relative risk of hypoglycaemia was influenced by key baseline characteristics, again using the different definitions.…”

Section: Introductionmentioning

confidence: 97%

“…In addition, previous analyses have shown that IDegLira is efficacious regardless of baseline characteristics, such as BMI 7 and glycated haemoglobin (HbA1c). 8 In the present analysis, we assessed whether the relative risk of hypoglycaemia was influenced by key baseline characteristics, again using the different definitions.…”

Section: Introductionmentioning

confidence: 99%

Rates of hypoglycaemia are lower in patients treated with insulin degludec/liraglutide (IDegLira) than with IDeg or insulin glargine, regardless of the hypoglycaemia definition used

Norwood¹,

Chen

Jaeckel

et al. 2017

Self Cite

AimsTo re‐analyse, using a series of alternative hypoglycaemia definitions, the data from 2 trials, DUAL I and V, in which the once‐daily, fixed ratio combination of insulin degludec/liraglutide (IDegLira) was compared with basal insulin therapy.Material and Methods Post hoc analyses of the DUAL I (patients uncontrolled on oral antidiabetic drugs) and DUAL V (patients uncontrolled on insulin glargine (IGlar) U100) trials were carried out using different definitions of hypoglycaemia and according to whether treatments were administered in the morning or afternoon. Rates of hypoglycaemia for the definitions of confirmed and American Diabetes Association (ADA)‐documented symptomatic hypoglycaemia were compared according to age, gender and body mass index (BMI).ResultsAlthough hypoglycaemia rates differed according to the alternative hypoglycaemia definitions, rates were consistently lower with IDegLira vs insulin degludec (IDeg) and IGlar U100. Despite glycated haemoglobin concentrations being lower with IDegLira at end of treatment, confirmed and nocturnal‐confirmed hypoglycaemia rates were lower for IDegLira vs IDeg and IGlar U100, irrespective of dosing time. The definitions of confirmed and ADA‐documented symptomatic hypoglycaemia did not have a significant effect on the treatment difference between IDegLira and IDeg, liraglutide or IGlar U100 when further assessed by baseline age, gender and BMI.ConclusionsTreatment with IDegLira, vs IDeg and IGlar U100, resulted in lower rates of hypoglycaemia regardless of dosing time and definition of hypoglycaemia used. The choice of hypoglycaemia definition did not influence the results of analyses when stratified by age, sex and BMI.