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

• Published in: Diabetes, obesity & metabolism Vol. 19; no. 6; pp. 858 - 865
• Main Authors: Harris, Stewart B., Kocsis, Győző, Prager, Rudolf, Ridge, Terry, Chandarana, Keval, Halladin, Natalie, Jabbour, Serge
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.06.2017; Wiley Subscription Services, Inc
• Subjects: Aged; Algorithms; Antidiabetics; Blood glucose; Blood Glucose - drug effects; Clinical trials; Diabetes; Diabetes mellitus; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - drug therapy; Drug Administration Schedule; Drug Combinations; Drug Therapy, Combination; efficacy; Equivalence Trials as Topic; Evidence-based medicine; Female; Glycated Hemoglobin A - drug effects; Humans; Hypoglycemia; Hypoglycemic Agents - administration & dosage; Insulin; insulin therapy; Insulin, Long-Acting - administration & dosage; Liraglutide - administration & dosage; Male; Metformin; Metformin - administration & dosage; Middle Aged; Original; Pioglitazone; randomized clinical trials; Safety; Thiazolidinediones - administration & dosage; Titration; Treatment Outcome; type 2 diabetes; randomized clinical trials; type 2 diabetes; insulin therapy; safety; efficacy
• ISSN: 1462-8902; 1463-1326
• DOI: 10.1111/dom.12892

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 < 7% in each arm. Mean fasting PG was similar after 32 weeks. Weight change was −1.0 kg vs −2.0 kg for once‐weekly vs twice‐weekly titration. Rates of severe or blood glucose‐confirmed symptomatic hypoglycaemia were low in both arms: 0.16 events/patient‐year of exposure (PYE) for once‐weekly, 0.76 events/PYE for twice‐weekly titration. Mean IDegLira dose at 32 weeks was 41 dose steps (41 U IDeg/1.48 mg Lira) for both arms. Overall adverse event rates were 207.8 and 241.3 events/100 PYE with once‐weekly and twice‐weekly titration, respectively. Conclusion A pragmatic titration algorithm with once‐weekly adjustments based on 2 PG readings resulted in a safety and glycaemic efficacy profile similar to that with twice‐weekly adjustments based on 3 preceding PG values in insulin‐naïve patients.