Efficacy and Safety of IDegLira in Participants with Type 2 Diabetes in India Uncontrolled on Oral Antidiabetic Drugs and Basal Insulin: Data from the DUAL Clinical Trial Program

Abstract

Introduction: The 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.

Methods: Three 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.

Results: In 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.

Conclusions: Results 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 registration: ClinicalTrials.gov identifier, NCT01336023 (DUAL I), NCT01392573 (DUAL II), NCT01618162 (DUAL IV).

Funding: Novo Nordisk A/S, Bagsvaerd, Denmark.

Keywords: IDegLira; Indian population; Type 2 Diabetes.

Figures

Fig. 1

Mean change in glycated hemoglobin (HbA1c) and end-of-trial HbA1c in the global study population and the Indian subpopulations of the DUAL I extension, DUAL IV and DUAL II trials (maximum 50 U) [8, 9, 11, 12]. Mean observed values are based on full analysis set and data inputted using the last observation carried forward (LOCF) method. Treatment difference is estimated from an analysis of covariance (ANCOVA) analysis. CI Confidence interval EOT end of trial, ETD estimated treatment difference, IDeg insulin degludec, IDegLira insulin degludec/liraglutide, Lira liraglutide, OAD oral antidiabetic drug

Fig. 2

Percentages of participants achieving the HbA1c target of <7% in the global study population and the Indian subpopulations of the DUAL I extension, DUAL IV and DUAL II trials (maximum 50 U) [8, 9, 11, 12]. Mean observed values are based on the full analysis set and LOCF inputted data. The odds ratio (OR) is estimated from a logistic regression analysis

Fig. 3

Mean change in body weight in the global study population and Indian subpopulations of the DUAL I extension, DUAL II and DUAL IV trials [8, 9, 11]. Maximum dose of IDeg was 50 U in DUAL II. Mean observed values are based on full analysis set and LOCF inputted data. Treatment difference is estimated from an ANCOVA analysis