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{TANDF_FPP}CMO/CMO_A_370737(NEW).3d (CMO) [First Proof]
Current Medical Research and Opinion
C213
Volume 25, Number 3 2008
this led to more missing data in the continuation all-patients-treated population(CAPT) analysis and fewer
patients contributing to the completers analysis in the monotherapy groups.
Conclusions:
In this study, initial treatment with sitagliptin, metformin, or the combination therapy of sitagliptin and
metformin provided substantial and durable glycemic control, improved markers of C12-cell function, and was
generally well-tolerated over 54 weeks in patients with type 2 diabetes.
Introduction
Patientstreatedwithasingleantihyperglycemicagent(AHA)oftenfailtoreach
glycemic goals or, once achieved, do not maintain these goals long term
1,2
.
Recent treatment recommendations from the Canadian Diabetes Association
include initiation of combination therapies for the treatment of patients with
marked hyperglycemia
3
. Furthermore, durability of treatment effect is not the
same among the AHAs. In a large clinical trial, treatment with either rosigli-
tazone or metformin demonstrated greater durability compared with the sulfo-
nylurea glyburide over 4 years
1
. Because type 2 diabetes is a progressive disease
and treatment requires prolonged lifestyle and/or pharmacologic management,
the long-term efficacy, durability, and safety of newer AHAs are important
considerations.
Sitagliptin, a dipeptidyl peptidase-4 inhibitor (DPP-4), is a newer treatment
for type 2 diabetes that was shown to be efficacious as monotherapy and as add-
on therapy in studies ranging from 12 to 52 weeks
4–13
.In a pooled safety analysis
in 6139 patients treated for up to 2 years, treatment with sitagliptin was well-
tolerated compared with non-sitagliptin treatment
14
. In patients with type 2
diabetes over 24 weeks, initial combination therapy with sitagliptin and met-
formin was shown to provide substantial and additive glycemic improvements
and was generally well-tolerated relative to placebo
15
. Further, the gastrointest-
inal tolerability profile of the initial combination of sitagliptin and metformin
was similar to that of metformin monotherapy. The objectives of the present
study were to evaluate the longer-term efficacy and safety of this initial combi-
nation therapy over 54 weeks in patients with type 2 diabetes. The aforemen-
tioned 24-week study
15
was continued for an additional 30 weeks to provide the
results for the 54-week study period.
Methods
This was a 54-week, multinational, randomized, double-blind, parallel-group
study (Clinicaltrials.gov: NCT00103857) consisting of a 24-week placebo-
controlledperiod(phaseA
15
)anda30-weekcontinuationperiod(continuation
phase). This study was conducted at 140 clinical sites in 18 countries (see
Appendix in Goldstein et al.
15
for a list of countries and study investigators).
Patients provided written informed consent to participate in this 54-week trial.
The protocol was reviewed and approved by the appropriate committees and
authorities and performed in accordance with the Declaration of Helsinki.
The design, inclusion and exclusion criteria, and primary results were pre-
viously published for the 24-week placebo-controlled portion of this study
15
.
Briefly, patients with type 2 diabetes (18–78 years of age) who were on or not
on an oral AHA at the screening visit were eligible to participate. After a
screening diet/exercise run-in period (including a drug wash-off period for
those on oral AHAs at screening) of 6–10 weeks (or 8–12 weeks for those on
thiazolidinediones), patients with HbA
1c
C217.5% to C2011.0% entered a 2-week,
2
54-week efficacy and safety of sitagliptin/metformin Williams-Herman et al. www.cmrojournal.com
!
2009 Informa UK Ltd
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