Efficacy and safety of the fixed-ratio combination of insulin degludec and liraglutide by baseline glycated hemoglobin, body mass index and age in Japanese individuals with type 2 diabetes: A subgroup analysis of two phase III trials.

AIMS/INTRODUCTION: To assess efficacy and safety of insulin degludec/liraglutide (IDegLira) in Japanese participants with type 2 diabetes across different baseline characteristics. MATERIALS AND METHODS: Data from two randomized controlled trials were used: DUAL I Japan (n = 819 insulin-naïve participants) and DUAL II Japan (n = 210 insulin-experienced participants). Outcomes were assessed according to baseline glycated hemoglobin ( HbA1c ; <8.0%, ≥8.0-<9.0%, ≥9.0%), body mass index (<25, ≥25-<30, ≥30 kg/m2 ) and age (<65, ≥65 years). RESULTS: In DUAL I Japan, reductions in HbA1c with IDegLira versus degludec and liraglutide were observed across all subgroups (treatment differences: -0.48% to -0.72% vs degludec, -0.29% to -0.73% vs liraglutide). Results were similar with IDegLira versus degludec in DUAL II Japan (treatment differences: -0.82% to -1.61%). Treatment-by-subgroup interactions were significant for IDegLira versus liraglutide for baseline HbA1c and age in DUAL I Japan, and for IDegLira versus degludec for baseline HbA1c in DUAL II Japan. In DUAL I Japan, IDegLira was associated with less weight gain than degludec in most subgroups. In DUAL II Japan, IDegLira was associated with a small mean weight loss (except for baseline HbA1c ≥9.0%) versus a small gain for degludec (except for age ≥65 years subgroup); treatment-by-subgroup interactions were not significant. Total daily insulin dose was lower with IDegLira versus degludec across all categories, except for age >65 years in DUAL II Japan. CONCLUSIONS: IDegLira reduced HbA1c in Japanese participants with type 2 diabetes across baseline HbA1c , body mass index and age categories, without unexpected safety issues.

IDegLira Improves Glycemic Control in Japanese Patients with Uncontrolled Type 2 Diabetes on Premixed Insulin Therapy.

INTRODUCTION: DUAL II Japan (NCT02911948) was a 26-week, phase 3a randomized, treat-to-target trial which compared the efficacy and safety of IDegLira with degludec in 210 Japanese patients with type 2 diabetes (T2D) uncontrolled on premixed or basal insulin therapy. The DUAL II Japan trial presented the opportunity for a post hoc analysis to examine the safety and efficacy of switching patients from a premixed regimen (containing both basal and bolus insulin components) to IDegLira. METHODS: Patients from DUAL II Japan were stratified according to prior insulin regimen (premixed or basal insulin). The following endpoints were assessed in this post hoc analysis by pre-trial insulin regimen: change in HbA1c, body weight, daily total insulin dose, nine-point self-measured blood glucose, and severe or blood glucose-confirmed hypoglycemia (defined as severe or plasma glucose less than 56 mg/dL). RESULTS: This post hoc analysis included 39 patients who switched from premixed insulin to IDegLira. The treatment effect in this population was independent of insulin type at baseline (premixed or basal; interaction test, P = 0.2535). In patients switching from premixed insulin to IDegLira, mean [standard deviation (SD)] HbA1c was 8.26% (0.73) at baseline and 6.68% (0.93) at week 26. Mean (SD) body weight was reduced by 1.5 (2.9) kg. At week 26, daily insulin dose was 34.2 dose steps. After 26 weeks, the mean prandial increment was smaller at all meals with IDegLira irrespective of pre-trial insulin regimen. Rate of hypoglycemic events was 2.59 events/patient-year of exposure over the 26 weeks. CONCLUSION: This post hoc study is the first to evaluate the switch from premixed insulin to IDegLira in patients with uncontrolled T2D. IDegLira initiation resulted in improved HbA1c and weight loss. This study offers insight into the effectiveness and safety of switching patients from premixed insulin therapy to IDegLira, and provides support for further investigation. TRIAL REGISTRATION: NCT02911948.

Fixed-ratio combination of insulin degludec and liraglutide (IDegLira) improves cardiovascular risk markers in patients with type 2 diabetes uncontrolled on basal insulin.

In this post hoc analysis we investigated the effects of insulin degludec/liraglutide fixed-ratio combination (IDegLira) versus comparators on cardiovascular (CV) risk markers in participants in the DUAL II (vs. insulin degludec), DUAL V (vs. insulin glargine 100 units/mL) and DUAL VII (vs. basal-bolus therapy) trials, grouped by sex, age (<65 years, ≥65 years) and diabetes duration (<10 years, ≥10 years). Treatment contrasts were in favour of IDegLira in many subgroups for changes from baseline in glycated haemoblogin (DUAL II, DUAL V), body weight (all three trials), systolic blood pressure (BP; all three trials), HDL cholesterol (DUAL VII) and LDL cholesterol (DUAL II, DUAL V). Higher heart rates were seen with IDegLira versus comparators (all three trials) plus significantly higher diastolic BP in men (DUAL V). Differences in treatment effect were seen between sexes in waist circumference (DUAL II), systolic BP (DUAL II, DUAL V) and triglycerides (DUAL VII), and between diabetes durations in LDL cholesterol (DUAL V). In conclusion, IDegLira is associated with a general improvement in CV risk markers compared with basal insulin or basal-bolus therapy after 26 weeks of treatment.

Left Ventricular Systolic Function Assessed by Global Longitudinal Strain is Impaired in Atrial Fibrillation Compared to Sinus Rhythm.

BACKGROUND: Atrial fibrillation (AF) is the most common aberrant cardiac arrhythmia. Many AF patients present with symptoms of dyspnea and fatigue, but have normal left ventricular ejection fraction (LVEF). PURPOSE: To determine the reproducibility of measurements of global longitudinal strain (GLS) and strain rate in patients with AF and examine if the arrhythmia is associated with abnormal LV strain and strain rate independent of age, sex, heart rate, LVEF and LV mass. We hypothesized that AF independently reduces ventricular systolic performance. METHODS: The study was conducted as a retrospective analysis of images from 150 randomly selected patients with AF compared to an equal number of subjects with sinus rhythm (SR) matched for age, sex, heart rate, LVEF and LV mass. Half of the patients had normal LVEF (LVEF > 50%) and half had reduced LVEF (LVEF < 50%). GLS and strain rate were measured in each group, as were quantitative LV volumes and standard systolic and diastolic parameters. Results: GLS was significantly impaired in patients with AF compared to subjects with SR, both in the overall population (-12.25 ± 4.1% vs. -16.13 ± 4.7%, p<0.0001), in patients with normal LVEF (-14.41 ± 3.9% vs. -19.42 ± 3.1%, p<0.0001) and in patients with reduced LVEF (-10.10 ± 3.1% vs. -12.85 ± 3.5%, p<0.0001).Linear regression and Bland Altman analyses demonstrated good intraobserver and interobserver agreement for measurements of GLS and strain rate parameters even in patients with AF.