Predictors of Insulin Initiation in Patients with Type 2 Diabetes: An
Analysis of the Look AHEAD Randomized Trial
Scott J. Pilla, MD, MHS
, Hsin-Chieh Yeh, PhD
, Stephen P. Juraschek, MD, PhD
Jeanne M. Clark, MD, MPH
, and Nisa M. Maruthur, MD, MHS
Department of Medicine, Division of General Internal Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, USA;
Department of Epidemiology, The Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA;
Welch Center for Prevention,
Epidemiology & Clinical Research, Baltimore, MD, USA.
BACKGROUND: The decision to initiate insulin in pa-
tients with type 2 diabetes is a challenging escalation of
care that requires an individualized approach. However,
the sociodemographic and clinical factors affecting insu-
lin initiation are not well understood.
OBJECTIVE: We sought to identify patient factors that
were independent predictors of insulin initiation among
participants in the Look AHEAD (Action for Health in
Diabetes) clinical trial.
DESIGN: Retrospective analysis of a randomized clinical
PARTICIPANTS: Beginning in 2001, Look AHEAD en-
rolled ambulatory U.S. adults with type 2 diabetes who
were overweight or obese and had a primary healthcare
provider. Participants were randomized (1:1) to an inten-
sive lifestyle intervention, or diabetes support and educa-
tion. This study examined 3913 participants across the
two trial arms who were not using insulin at baseline.
MAIN MEASURES: We used Cox proportional hazards
models to estimate the association between participant
characteristics and time to insulin initiation. We per-
formed time-varying adjustment for HbA1c measured
eight times over the 10-year study period, as well as for
multiple clinical and socioeconomic factors.
KEY RESULTS: A total of 1087 participants (27.8%) ini-
tiated insulin during a median follow-up of 8.0 years. Age
was inversely associated with insulin initiation (adjusted
hazard ratio [aHR] 0.88 per 10 years, P = 0.025). The risk
of insulin initiation was greater with a higher number of
diabetes complications (P < 0.001 for trend); chronic kid-
ney disease and cardiovascular disease were indepen-
dently associated with insulin initiation. There was a low-
er risk of insulin initiation in black (aHR 0.77, P = 0.008)
and Hispanic participants (aHR 0.66, P < 0.001) relative to
white participants. Socioeconomic factors were not asso-
ciated with insulin initiation.
CONCLUSIONS: Patient age, race/ethnicity, and diabetes
complications may influence insulin initiation in type 2
diabetes, independent of glycemic control. Future work is
needed to understand the drivers of racial differences in
antihyperglycemic treatment, and to identify patients who
benefit most from insulin.
KEY WORDS: diabetes mellitus, type 2; insulin/therapeutic use; risk
J Gen Intern Med 33(6):839–46
© Society of General Internal Medicine 2018
An ongoing challenge in the management of type 2 diabetes is
to provide individualized treatment of hyperglycemia in terms
of selection of medications and glycemic targets.
from the American Diabetes Association and European Asso-
ciation for the Study of Diabetes recommend insulin as one of
several second-line antihyperglycemic options after metfor-
min, or first-line therapy with hemoglobin A1c (HbA1c)
Insulin is commonly used in the treatment of type 2
diabetes, prescribed in over one fourth of ambulatory visits for
type 2 diabetes in the U.S. in 2012.
Although insulin may be
more effective than other antihyperglycemic medications in
lowering blood glucose, disadvantages include high cost, the
need for injections, and increased risk of weight gain and
Insulin initiation is an important transition of care from the
perspective of both providers and patients.
initiation is a strong preference and major motivating factor
among patients with type 2 diabetes,
and primary care
physicians list insulin initiation as one of the most difficult
aspects of diabetes care.
Patient-reported barriers to insulin
use include personal beliefs, difficulty of administration, and
cost of therapy.
Due to provider and patient factors, insulin is
not used in many patients with significant hyperglycemia.
Guidelines suggest that insulin use should be individual-
ized, but do not indicate the criteria for individualization.
Accordingly, providers treating patients with type 2 diabetes
have reported varying opinions about the risks and benefits of
insulin and the circumstances under which it should be
NIH Trial Registration Number
Look AHEAD (Action for Health in Diabetes) trial: NCT00017953
Electronic supplementary material The online version of this article
(https://doi.org/10.1007/s11606-017-4282-9) contains supplementary
material, which is available to authorized users.
Received August 30, 2017
Revised December 16, 2017
Accepted December 24, 2017
Published online January 19, 2018