Assessment of channeling bias among initiators of glucose-lowering drugs: A UK cohort study

Abstract

Mikkel Z Ankarfeldt,1,2 Brian L Thorsted,1 Rolf HH Groenwold,2,3 Erpur Adalsteinsson,1 M Sanni Ali,2–4 Olaf H Klungel2,3 1Novo Nordisk A/S, Bagsvaerd, Denmark; 2Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands; 3Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, University of Utrecht, Utrecht, the Netherlands; 4Nuffield Department of Orthopaedics, Rheumatology, Musculoskeletal Sciences, University of Oxford, Oxford, UK Background: Channeling bias may occur when a newly marketed drug and an established drug, despite similar indications, are prescribed to patients with different prognostic characteristics (ie, confounding).Aim: To investigate channeling bias and its impact on relative effectiveness of glucagon-like peptide-1 (GLP-1) analogs versus basal insulin and dipeptidyl peptidase-4 inhibitors (DPP-4i) versus sulfonylurea.Methods: In the UK Clinical Practice Research Datalink, patients with type 2 diabetes initiating treatment between 2006 and 2015 were included. Analyses were stratified by years since first prescription of GLP-1 and DPP-4i, respectively. The characteristics of GLP-1 versus insulin and DPP-4i versus sulfonylurea initiators were compared over time. After propensity score matching, the relative effectiveness regarding 6-month changes in glycated hemoglobin (HbA1c) and body weight was estimated.Results: In total, 8,398 GLP-1, 14,807 insulin, 24,481 DPP-4i, and 33,505 sulfonylurea initiators were identified. No major channeling was observed. Considerable overlap in distributions of characteristics allowed for propensity score-matched analyses. Relative effectiveness was similar across time. The overall relative effect of GLP-1 versus insulin showed no difference for HbA1c and relative increase in body weight (3.57 kg [95% confidence interval {CI}: 3.21, 3.92]) for insulin. The overall relative effect of DPP-4i versus sulfonylurea showed relative decrease in HbA1c (–0.34% [95% CI: –0.38, –0.30]) and increase in body weight (1.58 kg [95% CI: 1.38, 1.78]) for sulfonylurea.Conclusion: No major channeling was identified in the investigated glucose-lowering drugs. Relative effectiveness could be estimated already in the first year after launch and was consistent in the years thereafter. Keywords: channelling bias, channeling bias, glucose-lowering drugs, DPP-4i, GLP-1, type 2 diabetes, observational study, relative effectivenes