Superior efficacy with a fixed-ratio combination of insulin degludec and liraglutide (IDegLira) compared with insulin degludec and liraglutide in insulin-naïve Japanese patients with type 2 diabetes in a phase 3, open-label, randomized trial.

Publisher: Wiley-Blackwell Country of Publication: England NLM ID: 100883645 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1463-1326 (Electronic) Linking ISSN: 14628902 NLM ISO Abbreviation: Diabetes Obes Metab Subsets: MEDLINE

Original Publication: Oxford : Wiley-Blackwell, c1999-

Diabetes Mellitus, Type 2/*drug therapy ; Hypoglycemic Agents/*therapeutic use ; Insulin, Long-Acting/*therapeutic use ; Liraglutide/*therapeutic use; Adult ; Aged ; Aged, 80 and over ; Blood Glucose/analysis ; Drug Combinations ; Female ; Glycated Hemoglobin/analysis ; Humans ; Hypoglycemia/chemically induced ; Hypoglycemic Agents/administration & dosage ; Hypoglycemic Agents/adverse effects ; Insulin, Long-Acting/administration & dosage ; Insulin, Long-Acting/adverse effects ; Japan ; Liraglutide/administration & dosage ; Liraglutide/adverse effects ; Male ; Middle Aged

Aims: To investigate the efficacy and safety of insulin degludec/liraglutide (IDegLira) compared with its individual components in Japanese people with type 2 diabetes (T2D) uncontrolled on an oral antidiabetic drug (OAD).
Materials and Methods: This 52-week, open-label, multicentre, treat-to-target trial randomized participants (n = 819) 1:1:1 to IDegLira, liraglutide 1.8 mg or degludec, as add-on to their pre-trial OAD. The maximum IDegLira dose was 50 dose steps (50 U degludec/1.8 mg liraglutide), there was no maximum dose for degludec, and both were titrated based on individual blood glucose measurements.
Results: After 52 weeks, glycated haemoglobin (HbA1c) decreased by 26 mmol/mol with IDegLira vs 20 mmol/mol with degludec and liraglutide: estimated treatment differences were -6.91 mmol/mol (95% confidence interval [CI] -8.18; -5.64) and -5.30 mmol/mol (95% CI -6.58; -4.03), confirming non-inferiority of IDegLira to degludec and superiority of IDegLira to liraglutide (P < .0001 for both [primary endpoint]). Mean body weight changes were 2.9 kg, 4.1 kg and -1.0 kg with IDegLira, degludec and liraglutide, respectively, showing superiority of IDegLira versus degludec (P = .0001), but a significant difference in favour of liraglutide (P < .0001). Rates of severe or blood glucose-confirmed hypoglycaemia for IDegLira were lower versus degludec (rate ratio 0.48 [95% CI 0.35; 0.68]; P < .0001), but higher versus liraglutide (rate ratio 37.58 [95% CI 19.80; 71.31]; P < .0001). Mean daily total insulin dose was lower with IDegLira (27.7 U) versus degludec (34.8 U; P < .0001). Overall adverse event (AE) rates were similar. In total, 34.9%, 22.9% and 41.8% of IDegLira-, degludec- and liraglutide-treated participants experienced gastrointestinal AEs.
Conclusion: IDegLira was superior to degludec and liraglutide in terms of HbA1c reduction and superior to degludec in terms of body weight change and rates of hypoglycaemia in Japanese people with T2D.
(© 2019 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

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Keywords: basal insulin; liraglutide; hypoglycaemia; randomized trial; type 2 diabetes

ClinicalTrials.gov NCT02607306

0 (Blood Glucose)
0 (Drug Combinations)
0 (Glycated Hemoglobin A)
0 (Hypoglycemic Agents)
0 (IDegLira)
0 (Insulin, Long-Acting)
54Q18076QB (insulin degludec)
839I73S42A (Liraglutide)

Date Created: 20190814 Date Completed: 20201006 Latest Revision: 20221207

20240628

PMC6899795

10.1111/dom.13856

31407845