Henrik F. Thomsen

Once-daily initiation with biphasic insulin aspart 30 versus insulin glargine in patients with type 2 diabetes inadequately controlled with oral drugs: an open-label, multinational RCT

Abstract Objectives: To assess the efficacy and safety of biphasic insulin aspart 70/30 (BIAsp 30) and insulin glargine, administered once daily in subjects with type 2 diabetes inadequately controlled with oral anti-diabetic drugs. Research design and methods: In this 26-week, open-labeled, randomized, parallel-group, multinational, treat-to-target trial, 480 insulin-naïve subjects were randomized to receive either BIAsp 30 before dinner or insulin glargine at bedtime, both in combination with metformin and glimepiride. Trial registration: NCT00469092, ClinicalTrials.gov. Results: A total of 433 subjects completed the trial. Estimated mean reduction in HbA1c from baseline to end of treatment was −1.41% with BIAsp 30 and −1.25% with insulin glargine (BIAsp 30 – insulin glargine = −0.16%, 95% CI [−0.30; −0.02], p = 0.029). At the end of treatment, mean HbA1c was 7.1% and 7.3% for BIAsp 30 and insulin glargine, respectively. Significantly lower plasma glucose levels were observed with BIAsp 30 post-dinner (BIAsp 30 – insulin glargine = −0.52 mmol/L, 95% CI [−1.02; −0.03], p = 0.04) and at bedtime (BIAsp 30 – insulin glargine = −0.78 mmol/L, 95% CI [−1.25; −0.31], p < 0.01). The relative risk (RR) of experiencing a nocturnal hypoglycemic episode (00:00–06.00 a.m.) was significantly higher with BIAsp 30 than with insulin glargine (1.1 versus 0.5 episodes/year, RR = 2.41, 95% CI [1.34; 4.34], p = 0.003), but overall hypoglycemia rates were low. There were three major hypoglycemic episodes in each group. Conclusions: With respect to HbA1c, BIAsp 30 fulfilled the statistical criteria for non-inferiority and superiority to insulin glargine and, according to pre-defined criteria, the improvements in HbA1c are considered clinically equivalent. Subjects had an increased risk of minor nocturnal hypoglycemia with BIAsp 30. There were no differences in treatment satisfaction between the two groups.

Reductions in systolic blood pressure with liraglutide in patients with type 2 diabetes: Insights from a patient-level pooled analysis of six randomized clinical trials☆

AIMS To quantify the effect of liraglutide on systolic blood pressure (SBP) and pulse in patients with type 2 diabetes (T2D), and assess the influence of covariates on observed SBP reductions. METHODS A patient-level pooled analysis of six phase 3, randomized trials was conducted. RESULTS The analysis included 2792 randomized patients. In the intention-to-treat population (n=2783), mean [±SE] SBP reductions from baseline with liraglutide 1.2 mg (2.7 [0.8] mmHg) and 1.8 mg (2.9 [0.7] mmHg) once daily were significantly greater than with placebo (0.5 [0.9] mmHg; P=0.0029 and P=0.0004, respectively) after 26 weeks, and were evident after 2 weeks. Liraglutide was also associated with significantly greater SBP reductions than glimepiride and, at a dose of 1.8 mg, insulin glargine and rosiglitazone. SBP reductions with liraglutide weakly correlated with weight loss (Pearsons correlation coefficient: 0.08-0.12; P≤0.0148). No dependence of these reductions on concomitant antihypertensive medications was detected (P=0.1304). Liraglutide 1.2 and 1.8 mg were associated with mean increases in pulse of 3 beats per minute (bpm), versus a 1 bpm increase with placebo (P<0.0001 for each dose versus placebo). CONCLUSIONS Liraglutide reduces SBP in patients with T2D, including those receiving concomitant antihypertensive medication.

COMPARISON OF THE LONG-TERM EFFECTS OF LIRAGLUTIDE AND GLIMEPIRIDE MONOTHERAPY ON BONE MINERAL DENSITY IN PATIENTS WITH TYPE 2 DIABETES

OBJECTIVE Patients with type 2 diabetes have an increased risk of fragility fractures; the cause is unclear but is likely multifactorial. Some diabetes treatments induce bone loss, accentuating underlying skeletal fragility and increasing fracture risk. This subgroup analysis aimed to compare long-term effects of liraglutide and glimepiride on bone mineral density (BMD) in patients with type 2 diabetes. METHODS LEAD-3, a 52-week, double-blind, active-control, phase III, multicenter trial, investigated the efficacy of liraglutide (1.2 and 1.8 mg/day) versus glimepiride monotherapy in type 2 diabetes. A 52-week, open-label extension followed, in which participants remained on randomized therapy. A subgroup of participants underwent BMD measurement by dual-energy X-ray absorptiometry at baseline, 52, and 104 weeks. The main outcome measure was change from baseline in total body BMD at 52 and 104 weeks, assessed by analysis of covariance. RESULTS A total of 746 patients with type 2 diabetes aged 19 to 79 years were randomized into the main trial. Of these, 61 patients (20 assigned to liraglutide 1.8 mg/day, 23 to liraglutide 1.2 mg/day, 18 to glimepiride 8 mg/day) had BMD measurements. Baseline age, body mass index, diabetes duration, glycated hemoglobin, and total BMD were similar across treatment groups. There was no apparent difference in mean total BMD change from baseline in patients receiving liraglutide 1.8 or 1.2 mg/day or glimepiride 8 mg/day at 52 or 104 weeks. CONCLUSION In this small subgroup analysis, liraglutide monotherapy did not negatively affect total BMD in a 2-year prospective study, suggesting it may not exacerbate the consequences of bone fragility.