Lower rates of cardiovascular events and mortality associated with liraglutide use in patients treated with basal insulin: A DEVOTE subanalysis (DEVOTE 10)

AIM: To compare the associations between concomitant liraglutide use versus no liraglutide use and the risk of major adverse cardiovascular events (MACE) and all-cause mortality among patients receiving basal insulin (either insulin degludec [degludec] or insulin glargine 100 units/mL [glargine U100]) in the Trial Comparing Cardiovascular Safety of Insulin Degludec versus Insulin Glargine in Patients with Type 2 Diabetes at High Risk of Cardiovascular Events (DEVOTE). MATERIALS AND METHODS: Patients with type 2 diabetes and high cardiovascular risk were randomized 1:1 to degludec or glargine U100. Hazard ratios for MACE/mortality were calculated using a Cox regression model adjusted for treatment and time-varying liraglutide use at any time during the trial, without interaction. Sensitivity analyses were adjusted for baseline covariates including, but not limited to, age, sex, smoking and prior cardiovascular disease. RESULTS: At baseline, 436/7637 (5.7%) patients were treated with liraglutide; after baseline, 187/7637 (2.4%) started and 210/7637 (2.7%) stopped liraglutide. Mean liraglutide exposure from randomization was 530.2 days. Liraglutide use versus no liraglutide use was associated with significantly lower hazard rates for MACE [0.62 (0.41; 0.92)95%CI ] and all-cause mortality [0.50 (0.29; 0.88)95%CI ]. There was no significant difference in the rate of severe hypoglycaemia with versus without liraglutide use. Multiple sensitivity analyses yielded similar results. CONCLUSIONS: Use of liraglutide was associated with significantly lower risk of MACE and death in patients with type 2 diabetes and high cardiovascular risk using basal insulin

The clinical benefits of IDegLira in DUAL VII were achieved while using a simple regimen with fewer injections and dose adjustments compared with basal-bolus therapy

Background and aims:Complex treatment regimens, such as basal-bolus insulin therapy (BB), are associated with lower compliance, greater treatment burden and poor patient satisfaction. Complex regimens are also a major concern for physicians since they require more resources and clinical decisions, both of which become more problematic as type 2 diabetes (T2D) progresses. In DUAL VII, insulin degludec/liraglutide (IDegLira) resulted in non-inferior HbA1c reductions (as per the trial design), weight loss (-0.9 vs. 2.6 kg), and an 89% reduction in rates of hypoglycaemia compared with BB in patients with T2D. This post hoc analysis evaluated the treatment complexity of IDegLira vs. BB in terms of number of injections and dose adjustments.Materials and methods:In a 26-week, open-label trial, patients with T2D uncontrolled on metformin and 20-50 U insulin glargine 100 U/mL (IGlar U100) were randomised 1:1 to IDegLira (N=252) or BB (IGlar U100 + insulin aspart ≤4 times/day; N=254). IDegLira was initiated at 16 dose steps/units (U) (16 U insulin degludec + 0.58 mg liraglutide); initial IGlar U100 dose was the pre-trial dose (mean: 33 U). Both were titrated twice-weekly, based on the mean of three pre-breakfast self-monitored plasma glucose (SMPG) readings, to a target of 4-5 mmol/L. Insulin aspart was initiated at 4 U/main meal and titrated twice-weekly to a pre-prandial and bedtime SMPG target of 4-6 mmol/L. This analysis reports the observed mean number of insulin injections and dose adjustments during 26 weeks.ResultsDespite the lower starting basal insulin component dose with IDegLira vs. BB, the number of basal insulin dose adjustments were similar during treatment (Table). The mean number of bolus insulin adjustments increased steadily during the trial to 200 per patient (median [min; max]: 218 [1; 569]). 66.5% of patients in the BB group were receiving ≥3 bolus injections/day at Week 26 in addition to their basal insulin and SMPG measurements in connection with each injection. Conclusion: Burdensome regimens impact on patients’ quality of life, treatment adherence and ability to achieve good glycaemic control. Compared with BB, the clinical benefits of IDegLira (comparable HbA1c reduction, lower hypoglycaemia rates and weight loss) are achieved using a more convenient regimen in the DUAL VII study. In addition to the clinical benefits, this simple regimen has the advantages of fewer daily injections, SMPG readings and dose adjustments, requiring fewer clinical decisions.</p

Experiences, considerations and emotions relating to cardiogenetic evaluation in relatives of young sudden cardiac death victims

Relatives of young sudden cardiac death (SCD) victims are at increased risk of carrying a potentially fatal inherited cardiac disease. Hence, it is recommended to perform an autopsy on the victim and to refer his or her relatives to a cardiogenetics clinic for a full evaluation to identify those at risk and allow preventive measures to be taken. However, at present, the number of families attending a cardiogenetics clinic after the SCD of a young relative is low in the Netherlands. We performed a qualitative study and report on the experiences and attitudes of first-degree relatives who attended a cardiogenetics clinic for evaluation. In total, we interviewed nine first-degree relatives and one spouse of seven SCD victims about their experiences, considerations and emotions before attendance and at the first stage of the cardiogenetic evaluation before DNA results were available. Interviews were transcribed verbatim and analysed. Medical professionals did not have an important role in informing or referring relatives to a cardiogenetics clinic. Importantly, all participants indicated that they would have appreciated a more directive approach from medical professionals, because their mourning process hampered their own search for information and decision-making. A need to understand the cause of death and wanting to prevent another SCD event occurring in the family were the most important reasons for attending a clinic. There are possibilities to improve the information process and better support their decision-making. The multidisciplinary cardiogenetic evaluation was appreciated, but could be improved by minor changes in the way it is implemented