e204
COMMENT ON ZHANG ET AL.
Second-Line Agents for Glycemic Control
for Type 2 Diabetes: Are Newer Agents
Better? Diabetes Care 2014;37:13381345
Diabetes Care 2014;37:e204 | DOI: 10.2337/dc14-1041
We read with great interest the article
by Zhang et al. (1) in which they com-
pared in a model four second-line treat-
ment strategies following metformin
monotherapy: sulfonylurea, dipeptidyl
peptidase-4 inhibitor, GLP-1 agonist,
and insulin. They concluded that all
strategies produced similar glycemic
benets, but favored sulfonylurea from
a treatment cost perspective. Diabetes
models are used to simulate outcomes
that cannot be directly observed during
clinical trials. The results are often used
by payers to inform formulary decisions
and, as such, diabetes models play an
increasingly important role on the avail-
ability of therapeutic options to both
patients and prescribers.
Notable methodological achievement
in the study by Zhang et al. was that the
authors jointly estimated the underlying
e-LETTERS COMMENTS AND RESPONSES
probability of the HbA1c changes and the
initial treatment effects to support the
Markov model design. However, the key
assumption that underlying HbA1c uc-
tuation at baseline remains constant
throughout the patients life is not sup-
ported (2). In addition, reliance on the
rst 3-month treatment effect as the
main efcacy is a signicant limitation.
Longer-term studies have suggested
that capacity of various agents to sus-
tain glucose control varies (3). More-
over, due to heterogeneous treatment
response, the efcacy of these drugs
may not be sustained for some; but for
others, third-line therapies may be
Eli Lilly and Company, Indianapolis, IN
Corresponding author: Bradley H. Curtis, curtis_bradley_h@lilly.com.
2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for prot,
and the work is not altered.
Diabetes Care Volume 37, September 2014
Jay Bae, Bradley H. Curtis,
delayed more than 5 years in clinical
practice (4).
Using real-world patient data to esti-
mate treatment effects also raises the
concern that, in contrast to randomized
control clinical trials, real-world clinical
evidence will, in part, reect the selec-
tion of therapies based on the individual
needs of a patient. Adjusting for covari-
ates would not adequately correct for
this selection bias. Using propensity
score methods prior to estimating treat-
ment effects should have been included
to better account for this confounding.
Another important limitation is the
models ability to account for the effects
of hypoglycemia. The model adjusted
for hypoglycemia outcomes but did not
account for the cost associated with
management of hypoglycemia care. Re-
search shows that the cost of hypogly-
cemia hospitalization among patients
with type 2 diabetes treated with oral
medication to be $17,564 per event in
2008 (5). In addition, more recent evi-
dence suggests that nonsevere hypogly-
cemic events, which occur much more
frequently, incur an average cost of
$127 per person per event (6). Full ac-
counting of all health care costs associ-
ated with therapy, and not solely
medication acquisition costs, should
be used to more accurately evaluate
cost-effectiveness.
We encourage the further renement
of models that take into account the full
range of important clinical and economic
David M. Kendall, and Robert J. Heine
factors to better understand diabetes-
related health care burden.
Duality of Interest. J.B., B.H.C., D.M.K., and R.J.H.
are employees and shareholders of Eli Lilly and
Company, which is involved in the manufacture
and marketing of a variety of antihyperglycemia
agents that [at a therapeutic class level] would
be considered to be involved in the analysis
undertaken by Zhang et al. (e.g., insulin). No other
potential conicts of interest relevant to this
article were reported.
References
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