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Variables associated with HbA1c and weight reductions when adding liraglutide to multiple daily insulin injections in persons with type 2 diabetes (MDI Liraglutide trial 3).

ABSTRACT: Objective:To evaluate variables associated with hemoglobin A1c (HbA1c) and weight reduction when adding liraglutide to persons with type 2 diabetes treated with multiple daily insulin injections (MDI). Research design and methods:This was a reanalysis of a previous trial where 124 patients were enrolled in a double-blind, placebo-controlled, multicenter randomized trial carried out over 24 weeks. Predictors for effect on change in HbA1c and weight were analyzed within the treatment group and with concurrent interaction analyses. Correlation analyses for change in HbA1c and weight from baseline to week 24 were made. Results:The mean age at baseline was 63.7 years, 64.8% were men, the mean number of insulin injections was 4.4 per day, the mean daily insulin dose was 105 units and the mean HbA1c was 74.5?mmol/mol (9.0%). The mean HbA1c and weight reductions were 12.3?mmol/mol (1.13%; P<0.001) and 3.8?kg (P<0.001) greater in liraglutide than placebo-treated persons. There was no significant predictor for greater effect on HbA1c that existed in all analyses (univariate, multivariate and interaction analyses against controls). For a greater weight reduction when adding liraglutide, a lower HbA1c level at baseline was a predictor (liraglutide group P=0.002, P=0.020 for liraglutide group vs placebo). During follow-up in the liraglutide group, no significant correlation was found between change in weight and change in HbA1c (r=0.09, P=0.46), whereas a correlation existed between weight and insulin dose reduction (r=0.44, P<0.001). Conclusion:Weight reduction becomes greater when adding liraglutide in patients with type 2 diabetes treated with MDI who had a lower HbA1c level compared with those with a higher HbA1c level. There was no correlation between reductions in HbA1c and weight when liraglutide was added, that is, different patient groups responded with HbA1c and weight reductions. Trial registration number:EudraCT nr: 2012-001941-42.

SUBMITTER: Dahlqvist S

PROVIDER: S-EPMC5841497 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Variables associated with HbA1c and weight reductions when adding liraglutide to multiple daily insulin injections in persons with type 2 diabetes (MDI Liraglutide trial 3).

Dahlqvist Sofia S Ahlén Elsa E Filipsson Karin K Gustafsson Thomas T Hirsch Irl B IB Tuomilehto Jaakko J Imberg Henrik H Ahrén Bo B Attvall Stig S Lind Marcus M

BMJ open diabetes research & care 20180224 1

<h4>Objective</h4>To evaluate variables associated with hemoglobin A1c (HbA1c) and weight reduction when adding liraglutide to persons with type 2 diabetes treated with multiple daily insulin injections (MDI).<h4>Research design and methods</h4>This was a reanalysis of a previous trial where 124 patients were enrolled in a double-blind, placebo-controlled, multicenter randomized trial carried out over 24 weeks. Predictors for effect on change in HbA1c and weight were analyzed within the treatmen ...[more]

PMID: 29527308

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Project description:Study questionWhat are the effects of liraglutide, an incretin based treatment, on glycaemic control in people with type 2 diabetes treated with multiple daily insulin injections?MethodsThe study was a randomised, double blind, placebo controlled trial with a parallel group design carried out at 13 hospital based outpatient clinics and one primary care unit in Sweden. Patients were considered eligible for inclusion if they had type 2 diabetes and inadequate glycaemic control (HbA1c concentrations ≥ 58 mmol/mol (7.5%) and ≤ 102 mmol/mol (11.5%)), a body mass index of 27.5-45 kg/m(2), and required multiple daily insulin injections. Overall, 124 participants were randomised 1:1 to subcutaneous liraglutide or placebo by minimisation allocation. The main outcome measure was change in HbA1c level from baseline to week 24.Study answer and limitationsLiraglutide was associated with a significant reduction of 16.9 mmol/mol (1.5%) in HbA1c versus 4.6 mmol/mol (0.4%) for placebo, difference -12.3 mmol/mol (95% confidence interval -15.8 to -8.8 mmol/mol; -1.13%, -1.45 to -0.81 mmol/mol). Body weight was significantly reduced in participants in the liraglutide compared with placebo group (3.8 v 0.0 kg, difference -3.8, -4.9 to -2.8 kg), and total daily insulin doses were significantly reduced, by 18.1 units and 2.3 units (difference -15.8, -23.1 to -8.5 units). Reductions in mean and standard deviation of glucose levels estimated by masked continuous glucose monitoring were significantly greater in the liraglutide group than placebo group (-1.9 and -0.5 mmol/L). Neither group experienced severe hypoglycaemic events nor were there any significant differences in symptomatic or asymptomatic non-severe hypoglycaemia (<4.0 or <3.0 mmol/L). The mean number of non-severe symptomatic hypoglycaemic events (<4.0 mmol/L) during follow-up was 1.29 in the liraglutide group and 1.24 in the placebo group (P=0.96). One of the study's limitations was its relatively short duration. Sustained effects of liraglutide have, however, been found over lengthier periods in connection with other treatment regimens. Cardiovascular safety and potential adverse events during longer exposure to liraglutide need to be evaluated. Nausea was experienced by 21 (32.8%) participants in the liraglutide group and 5 (7.8%) in the placebo group and 3 (5%) and 4 (7%) participants in these groups, respectively, had any serious adverse event.What this study addsAdding liraglutide to multiple daily insulin injections in people with type 2 diabetes improves glycaemic control without an increased risk of hypoglycaemia, reduces body weight, and enables patients to lower their insulin doses.Funding, competing interests, data sharingThis study was an investigator initiated trial, supported in part by Novo Nordisk and InfuCare. Potential competing interests have been reported and are available on the bmj.com.Study registrationEudraCT 2012-001941-42.

Project description:AimUse of the glucagon-like peptide 1 receptor agonist liraglutide has been shown to reduce weight. Different types of anthropometric measurements can be used to measure adiposity. This study evaluated the effect of liraglutide on sagittal abdominal diameter, waist circumference, waist-to-hip ratio and adiponectin levels in people with type 2 diabetes (T2D) treated with multiple daily insulin injections (MDI).Materials and methodsIn the multicentre, double-blind, placebo-controlled MDI-liraglutide trial, 124 individuals with T2D treated with MDI were randomized to either liraglutide or placebo. Basal values of weight, waist circumference, waist-to-hip ratio, sagittal abdominal diameter and adiponectin were compared with measurements at 12 and 24 weeks after randomization.ResultsBaseline-adjusted mean weight loss was 3.8 ± 2.9 kg greater in liraglutide than placebo-treated individuals (p < 0.0001). Waist circumference was reduced by 2.9 ± 4.3 cm and 0.2 ± 3.6 cm in the liraglutide and placebo groups, respectively, after 24 weeks (baseline-adjusted mean difference: 2.6 ± 4.0 cm, p = 0.0005). Corresponding reductions in sagittal abdominal diameter were 1.1 ± 1.7 cm and 0.0 ± 1.8 cm (baseline-adjusted mean difference: 1.1 ± 1.7 cm, p = 0.0008). Hip circumference was reduced in patients randomized to liraglutide (baseline-adjusted mean difference between treatment groups: 2.8 ± 3.8 cm, p = 0.0001), but there was no significant difference between the groups in either waist-to-hip ratio (baseline-adjusted mean difference: 0.0 ± 0.04 cm, p = 0.51) or adiponectin levels (baseline-adjusted mean difference: 0.8 ± 3.3 mg L-1, p = 0.17). Lower HbA1c and mean glucose levels measured by masked continuous glucose monitoring at baseline were associated with greater effects of liraglutide on reductions in waist circumference and sagittal abdominal diameter.ConclusionsIn patients with T2D, adding liraglutide to MDI may reduce abdominal and hip obesity to a similar extent, suggesting an effect on both visceral and subcutaneous fat. Liraglutide had greater effects on reducing abdominal obesity in patients with less pronounced long-term hyperglycaemia but did not affect adiponectin levels.

Project description:IntroductionThe effects of the GLP-1 analogue liraglutide on time in hypoglycaemia, time in hyperglycaemia, and time in range for type 2 diabetes patients initially treated with multiple daily insulin injections (MDI) were investigated. Variables associated with hypoglycaemia in the current population were also identified.MethodsAnalyses were based on data from a previously performed double-blind, placebo-controlled trial in which 124 MDI-treated patients with type 2 diabetes were randomized to liraglutide or placebo. Masked continuous glucose monitoring (CGM) was performed at baseline and week 24 in 99 participants.ResultsThe mean time in hypoglycaemia was similar for participants receiving liraglutide and those receiving placebo after 24 weeks of treatment. Mean time in target was greater in the liraglutide group than in the placebo group: 430 versus 244 min/24 h (p < 0.001) and 960 versus 695 min/24 h (p < 0.001) for the two glycaemic ranges considered, 4-7 mmol/l and 4-10 mmol/l, respectively. Mean time in hyperglycaemia was lower in the liraglutide group: 457 versus 723 min/24 h (p = 0.001) and 134 versus 264 min/24 h (p = 0.023) for the two cutoffs considered, > 10 mmol/l and > 14 mmol/l, respectively. Lower mean glucose level, lower C-peptide, and higher glucose variability were associated with an increased risk of hypoglycaemia in both treatment groups. Higher proinsulin level was associated with a lower risk of hypoglycaemia in the liraglutide group.ConclusionFor type 2 diabetes patients initially treated with MDI, introducing liraglutide had a beneficial effect on glucose profiles estimated by masked CGM. Mean glucose level, glycaemic variability, C-peptide, and proinsulin level influenced the risk of hypoglycaemia in this population.Trial registrationClinicalTrials.gov, number (EudraCT nr: 2012-001941-42).FundingNovo Nordisk funded this study. The Diabetes Research Unit, NU-Hospital Group funded the journal's Rapid Service Fee.

Project description:Having demonstrated short-term weight loss with liraglutide in this group of obese adults, we now evaluate safety/tolerability (primary outcome) and long-term efficacy for sustaining weight loss (secondary outcome) over 2 years.A randomized, double-blind, placebo-controlled 20-week study with 2-year extension (sponsor unblinded at 20 weeks, participants/investigators at 1 year) in 19 European clinical research centers.A total of 564 adults (n=90-98 per group; body mass index 30-40?kg?m(-2)) enrolled, 398 entered the extension and 268 completed the 2-year trial. Participants received diet (500?kcal?deficit per day) and exercise counseling during 2-week run-in, before being randomly assigned (with a telephone or web-based system) to once-daily subcutaneous liraglutide (1.2, 1.8, 2.4 or 3.0?mg, n=90-95), placebo (n=98) or open-label orlistat (120?mg × 3, n=95). After 1 year, liraglutide/placebo recipients switched to liraglutide 2.4?mg, then 3.0?mg (based on 20-week and 1-year results, respectively). The trial ran from January 2007-April 2009 and is registered with Clinicaltrials.gov, number NCT00480909.From randomization to year 1, liraglutide 3.0?mg recipients lost 5.8?kg (95% confidence interval 3.7-8.0) more weight than those on placebo and 3.8?kg (1.6-6.0) more than those on orlistat (P?0.0001; intention-to-treat, last-observation-carried-forward). At year 2, participants on liraglutide 2.4/3.0?mg for the full 2 years (pooled group, n=184) lost 3.0?kg (1.3-4.7) more weight than those on orlistat (n=95; P<0.001). Completers on liraglutide 2.4/3.0?mg (n=92) maintained a 2-year weight loss of 7.8?kg from screening. With liraglutide 3.0?mg, 20-week body fat decreased by 15.4% and lean tissue by 2.0%. The most frequent drug-related side effects were mild to moderate, transient nausea and vomiting. With liraglutide 2.4/3.0?mg, the 2-year prevalence of prediabetes and metabolic syndrome decreased by 52 and 59%, with improvements in blood pressure and lipids.Liraglutide is well tolerated, sustains weight loss over 2 years and improves cardiovascular risk factors.

Dataset Information

Variables associated with HbA1c and weight reductions when adding liraglutide to multiple daily insulin injections in persons with type 2 diabetes (MDI Liraglutide trial 3).

Publications

Variables associated with HbA1c and weight reductions when adding liraglutide to multiple daily insulin injections in persons with type 2 diabetes (MDI Liraglutide trial 3).

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