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Safety and efficacy of IDegLira titrated once weekly versus twice weekly in patients with type 2 diabetes uncontrolled on oral antidiabetic drugs: DUAL VI randomized clinical trial.

ABSTRACT: AIMS:To compare the safety and efficacy of a simpler titration algorithm for insulin degludec/liraglutide (IDegLira) with that used in previous DUAL trials in insulin-naïve patients with type 2 diabetes. RESEARCH DESIGN AND METHODS:This 32-week, open-label, non-inferiority trial randomized adults with type 2 diabetes uncontrolled on metformin?±?pioglitazone to receive IDegLira, titrated either once weekly, based on the mean of 2 pre-breakfast plasma glucose (PG) readings (n?=?210), or twice weekly, based on the mean of 3 pre-breakfast PG readings (n?=?210). RESULTS:Mean HbA1c decreased from 8.2% (65?mmol/mol) to 6.1% (43?mmol/mol) with once-weekly titration and from 8.1% (65?mmol/mol) to 6.0% (42?mmol/mol) with twice-weekly titration; non-inferiority was confirmed (estimated treatment difference: 0.12% [-0.04; 0.28]95%CI , 1.30?mmol/mol [-0.41; 3.01]95%CI ). Approximately 90% of patients achieved HbA1c?

SUBMITTER: Harris SB

PROVIDER: S-EPMC5484356 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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Safety and efficacy of IDegLira titrated once weekly versus twice weekly in patients with type 2 diabetes uncontrolled on oral antidiabetic drugs: DUAL VI randomized clinical trial.

Harris Stewart B SB Kocsis Győző G Prager Rudolf R Ridge Terry T Chandarana Keval K Halladin Natalie N Jabbour Serge S

Diabetes, obesity & metabolism 20170303 6

<h4>Aims</h4>To compare the safety and efficacy of a simpler titration algorithm for insulin degludec/liraglutide (IDegLira) with that used in previous DUAL trials in insulin-naïve patients with type 2 diabetes.<h4>Research design and methods</h4>This 32-week, open-label, non-inferiority trial randomized adults with type 2 diabetes uncontrolled on metformin ± pioglitazone to receive IDegLira, titrated either once weekly, based on the mean of 2 pre-breakfast plasma glucose (PG) readings (n = 210) ...[more]

PMID: 28124817

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Project description:IntroductionThe efficacy and safety of insulin degludec/liraglutide (IDegLira) has been evaluated in the Dual Action of Liraglutide and Insulin Degludec in Type 2 Diabetes (DUAL) phase 3 clinical trial program. In this post hoc analysis, we compared the efficacy and safety of IDegLira in the Indian subpopulation with the results from the global trial population of DUAL trials. The analysis includes participants uncontrolled on oral antidiabetic drugs (OADs) in DUAL I and DUAL IV and participants uncontrolled on basal insulin and OADs in DUAL II.MethodsThree phase 3 trials were included in the analysis: DUAL I extension (IDegLira vs. insulin degludec or liraglutide 1.8 mg in participants uncontrolled on metformin ± pioglitazone; 52 weeks; n = 1663), DUAL IV (IDegLira vs. placebo as an add-on to a regimen of sulfonylurea ± metformin; 26 weeks; n = 435) and DUAL II (IDegLira vs. insulin degludec in participants uncontrolled on basal insulin + OADs; 26 weeks; n = 398). There were 251, 64 and 64 participants, respectively, at the Indian sites.ResultsIn the Indian subpopulations, the reductions in glycated hemoglobin (HbA1c) with IDegLira were substantial [DUAL I: 1.96% (-21 mmol/mol); DUAL IV: -1.40% (-15 mmol/mol); DUAL II: -2.20% (-24 mmol/mol)] and significantly greater than those in the comparators in each trial. IDegLira was generally weight-neutral after the administration of OADs (-0.3 and +0.6 kg in DUAL I and DUAL IV) and resulted in weight loss after the administration of basal insulin (-2.1 kg in DUAL II). Hypoglycemia rates were 1.98, 1.08 and 0.37 events/patient-years of exposure (PYE) for IDegLira, insulin degludec and liraglutide in DUAL I, 4.06 and 0.36 events/PYE for IDegLira and placebo in DUAL IV and 1.16 and 0.83 events/PYE with IDegLira and insulin degludec in DUAL II.ConclusionsResults from the Indian subpopulations reflect those of the global study populations, supporting IDegLira as an effective and safe treatment option for people with type 2 diabetes inadequately controlled on OADs or basal insulin + OADs in the South Asian population.Trial registrationClinicalTrials.gov identifier, NCT01336023 (DUAL I), NCT01392573 (DUAL II), NCT01618162 (DUAL IV).FundingNovo Nordisk A/S, Bagsvaerd, Denmark.

Project description:A 48-week, multicenter, randomized, double-blind, double-dummy, active-controlled, non-inferiority trial (the TWICE study) conducted in Japanese primary osteoporosis patients with a high risk of fractures demonstrated that a 28.2-?g twice-weekly regimen of teriparatide can provide comparable efficacy to a 56.5-?g once-weekly regimen of teriparatide, while also improving safety.IntroductionWhile a 56.5-?g once-weekly regimen of teriparatide has high efficacy for osteoporosis, treatment continuation rates are low, with one of the major causes being adverse drug reactions such as nausea or vomiting. The TWICE study was therefore conducted to investigate whether a twice-weekly regimen with 28.2-?g teriparatide can provide comparable efficacy to the 56.5-?g once-weekly regimen while improving safety.MethodsA 48-week, multicenter, randomized, double-blind, double-dummy, active-controlled, non-inferiority trial was conducted in Japan. Patients with primary osteoporosis aged ??65 years at high risk of fractures (n?=?553) were randomly allocated to the 28.2-?g twice-weekly group (n?=?277) or the 56.5-?g once-weekly group (n?=?276). The primary endpoint was the percentage change in lumbar spine (L2-L4) bone mineral density (BMD) at final follow-up.ResultsThe percentage changes in lumbar spine (L2-L4) BMD at final follow-up in the 28.2-?g twice-weekly and 56.5-?g once-weekly groups were 7.3% and 5.9%, respectively; the difference (95% confidence interval [CI]) in percentage change was 1.3% (0.400-2.283%). Since the lower limit of the 95% CI was above the pre-specified non-inferiority margin (-?1.6%), non-inferiority of the 28.2-?g twice-weekly group was demonstrated. Adverse drug reactions were significantly less frequent in the 28.2-?g twice-weekly group (39.7% vs 56.2%; p?<?0.01); the incidence of major adverse drug reactions was lower, and the number of subjects who discontinued due to adverse drug reactions was less in the 28.2-?g twice-weekly group.ConclusionsA 28.2-?g twice-weekly regimen of teriparatide can provide comparable efficacy to a 56.5-?g once-weekly regimen while improving safety.Clinical trial registrationJapicCTI-163477 .

Project description:Anaemia is a common complication of chronic kidney disease and prevalence increases with declining renal function. Renal anaemia has significant implications for the well-being and quality of life of patients and impacts on morbidity and mortality. Anaemia can be well managed by therapy with erythropoiesis-stimulating agents (ESAs). Previous clinical trials have shown that the only human cell-line-derived ESA, epoetin delta, is well tolerated and effective in maintaining haemoglobin levels in anaemic patients with chronic kidney disease. The half-life of epoetin delta suggests that administration of this agent is feasible once weekly and once every two weeks. We report on the design and rationale of a trial to compare once weekly vs. twice weekly, and once weekly vs. once every two weeks dosing of epoetin delta.This is a randomized, open-label, multicentre trial. Patients aged 18 years or above with chronic kidney disease (Stages 3-5) are eligible to enter this trial. Two groups of patients form the trial population, those naïve to ESA therapy and those previously stable on ESA therapy. There are two primary objectives of this trial: 1) to demonstrate non-inferiority between twice weekly and once weekly dosing of epoetin delta in previously naïve patients (assessed by haemoglobin at Week 24); 2) to demonstrate non-inferiority between once weekly and once every two weeks dosing in previously stable patients (assessed by average haemoglobin over Weeks 16-24). Among the secondary analyses will be assessments of haematocrit, number(%) of patients meeting predefined targets for haemoglobin and haematocrit levels, and comparisons of average dose. All patients will receive study medication for 24 weeks and dose will be adjusted according to a predefined algorithm to achieve and maintain haemoglobin >or= 11 g/dL. All patients completing this trial are eligible to enter a 2-year follow-up study to enable monitoring of emergent adverse events, anti-erythropoietin antibody responses, maintenance of efficacy and changes in diabetic retinopathy status.To our knowledge, this trial is the first to randomize ESA-naïve patients to different dosing regimens of the same ESA. Data generated will help in guiding the most appropriate dosing frequency for epoetin delta, particularly in those patients new to epoetin delta therapy.ClinicalTrials.gov: NCT00450333.

Project description:BackgroundCyslipidemia and type 2 diabetes are two of the most significant risk factors for the development of cardiovascular disease. Measurement of lipoprotein subclasses provides important information about derangements in lipid metabolism and helps refine cardiovascular risk assessment. Exenatide, a glucagon-like peptide 1 receptor agonist, improved glycemic control, obesity, hypertension, and dyslipidemia in patients with type 2 diabetes in clinical trials.MethodsIn the DURATION-1 trial, patients with type 2 diabetes were treated with exenatide once weekly or twice daily for 30 weeks. This post hoc analysis evaluated the impact of exenatide on lipoprotein subclasses in 211 DURATION-1 patients using vertical auto profile methodology and the Statistical Package for the Social Sciences general linear model adjusted for glycosylated hemoglobin (HbA(1c)) and weight.ResultsBaseline lipids and high sensitivity C-reactive protein were normal overall based on the standard lipid panel. Once-weekly exenatide reduced apolipoprotein B and the apolipoprotein B to apolipoprotein A1 ratio (P < 0.05), independent of glycemic improvement and weight loss. A significant shift in lipoprotein pattern away from small, dense low-density lipoprotein-4 cholesterol was also observed (P < 0.05). Exenatide once weekly increased high-density lipoprotein-2 cholesterol, even after adjustment for changes in HbA(1c) and weight (P < 0.05). Triglycerides, very low-density lipoprotein cholesterol, and high sensitivity C-reactive protein were reduced with both the once-weekly and twice-daily exenatide regimens (P < 0.05).ConclusionIn this post hoc analysis, exenatide significantly improved a number of cardiovascular risk markers. Continuous exenatide exposure with exenatide once weekly elicited a greater response than did immediate-release exenatide twice daily, generally independent of glycemic improvement and weight loss. Thus, in addition to improving glycemic control, exenatide induced favorable changes in lipid and lipoprotein metabolism and decreased systemic inflammation.

Dataset Information

Safety and efficacy of IDegLira titrated once weekly versus twice weekly in patients with type 2 diabetes uncontrolled on oral antidiabetic drugs: DUAL VI randomized clinical trial.

Publications

Safety and efficacy of IDegLira titrated once weekly versus twice weekly in patients with type 2 diabetes uncontrolled on oral antidiabetic drugs: DUAL VI randomized clinical trial.

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