Time to Treatment Intensification After Monotherapy Failure and Its Association With Subsequent Glycemic Control Among 93,515 Patients With Type 2 Diabetes

Urvi Desai, Noam Y. Kirson, Jennifer Kim, Kamlesh Khunti, Sarah King, Erich Trieschman, Michael Hellstern, Phillip R. Hunt, Jayanti Mukherjee

Abstract:

OBJECTIVE
The goal of this study was to evaluate the association between the timing of
treatment intensification and subsequent glycemic control among patients with
type 2 diabetes in whom monotherapy fails.
RESEARCH DESIGN AND METHODS
This retrospective analysis of the U.K. Clinical Practice Research Datalink database
focused on patients with type 2 diabetes and one or more HbA1c measurements
‡7% (‡53 mmol/mol) after ‡3 months of metformin or sulfonylurea monotherapy (first measurement meeting these criteria was taken as the study index date).
Baseline (6 months before the index date) characteristics were stratified by time
from the index date to intensification (early: <12 months; intermediate: 12 to
<24 months; late: 24 to <36 months). Intensification was defined as initiating after
the index date one or more noninsulin antidiabetes medication in addition to
metformin or a sulfonylurea. Association between time to intensification and subsequent glycemic control (first HbA1c <7% [<53 mmol/mol] after intensification)
was evaluated using Kaplan-Meier analyses and Cox proportional hazard models
that accounted for baseline differences.
RESULTS
Of the 93,515 patients who met the study criteria (mean age 60 years; ∼59% male;
80% taking metformin), 23,761 (25%) intensified <12 months after the index date;
11,908 (13%) intensified after 12 to <24 months; and 7,146 (8%) intensified after
24 to <36 months. Patients who intensified treatment ‡36 months after the index
date (n 5 9,638 [10%]) and those with no evidence of treatment intensification
during the observable follow-up period (n 5 41,062 [44%]) were not included in
further analyses. The median times from intensification to control were 20.0,
24.1, and 25.7 months, respectively, for the early, intermediate, and late intensification cohorts. After adjustment for baseline differences, the likelihood of attaining
glycemic control was 22% and 28% lower for patients in the intermediate and late
intensification groups, respectively, compared with those intensifying early (P <
0.0001).
CONCLUSIONS
Earlier treatment intensification is associated with shorter time to subsequent
glycemic control, independent of whether patients initiate first-line treatment
with metformin or a sulfonylurea.