IDegLira Versus Alternative Intensification Strategies in Patients with Type 2 Diabetes Inadequately Controlled on Basal Insulin Therapy

Nick Freemantle, Muhammad Mamdani, Tina Vilsbøll, Jens Harald Kongsø, Kajsa Kvist, Stephen C Bain, Nick Freemantle, Muhammad Mamdani, Tina Vilsbøll, Jens Harald Kongsø, Kajsa Kvist, Stephen C Bain

Abstract

Introduction: IDegLira is a once-daily combination of insulin degludec (IDeg) and liraglutide. Trials directly comparing IDegLira with alternative strategies for intensifying basal insulin are ongoing. While awaiting results, this analysis compared indirectly how different strategies affected glycated hemoglobin (HbA1c) and other outcomes.

Methods: A pooled analysis of five completed Novo Nordisk randomized clinical trials in patients with type 2 diabetes inadequately controlled on basal insulin was used to compare indirectly IDegLira (N = 199) with: addition of liraglutide to basal insulin (N = 225) [glucagon-like peptide-1 receptor agonist (GLP-1RA) add-on strategy]; basal-bolus (BB) insulin [insulin glargine (IGlar) + insulin aspart] (N = 56); or up-titration of IGlar (N = 329). A supplementary analysis was performed with the BB arm including patients who received IGlar or IDeg as basal insulin in the relevant trial (N = 210). All trials had comparable inclusion/exclusion criteria and baseline characteristics. Individual patient-level data were analyzed using multivariable statistical models with potential baseline heterogeneity accounted for using explanatory variables.

Results: At end of study, differences between IDegLira and BB or up-titrated IGlar, respectively, were as follows: reduction in HbA1c -0.30%, 95% confidence interval (-0.58; -0.01) and -0.65% (-0.83; -0.47); change in body weight -6.89 kg (-7.92; -5.86) and -4.04 kg (-4.69; -3.40) all in favor of IDegLira. Confirmed hypoglycemia rate was 122.8 (90.7; 166.1), 1060.8 (680.2; 1654.4), and 286.1 (231.1; 354.1) events/100 patient-years for IDegLira, BB, and up-titrated IGlar, respectively. Odds ratios for achieving HbA1c <7.0%, <7.0% without hypoglycemia, and <7.0% without hypoglycemia and no weight gain were greater with IDegLira versus up-titrated IGlar. The supplementary analysis yielded similar results to the main analysis. Results with IDegLira were similar to those for the 'GLP-1RA add-on' arm.

Conclusion: These results suggest that IDegLira may be more effective, with lower hypoglycemia rates and less weight gain, than up-titrated basal insulin or BB in patients uncontrolled on basal insulin.

Keywords: Basal insulin; IDegLira; Insulin degludec; Intensification; Liraglutide; Type 2 diabetes.

Figures

Fig. 1
Fig. 1
Summary of method: pooled indirect analysis of IDegLira OD versus other insulin intensification strategies in patients uncontrolled on basal insulin [, –21]. ANCOVA analysis of covariance, BMI body mass index, DPP-4 dipeptidyl peptidase-4 inhibitor, HbA1c glycated hemoglobin, HDL high-density lipoprotein, IAsp insulin aspart, IDeg insulin degludec, IDegLira insulin degludec/liraglutide, IDet insulin detemir, IGlar insulin glargine, LDL low-density lipoprotein, lira liraglutide, met metformin, OAD oral antidiabetic drug, OD once daily, pio pioglitazone, SBP systolic blood pressure, SU sulfonylurea, TID three-times daily

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