XML Template (2009) [7.9.2009–9:27am] [1–14]
{TANDF_FPP}CMO/CMO_A_370737(NEW).3d (CMO) [First Proof]
Current Medical Research and OpinionC213 Volume 25, Number 3 2008
0300-7995 Article 4881/370737
doi:10.1185/03007990802705679 All rights reserved: reproduction in whole or part not permitted
Original article
Efficacy and safety of initial combination therapy
with sitagliptin and metformin in patients with
type 2 diabetes: a 54-week study
,
Debora Williams-Herman
ABSTRACT
Jeremy Johnson
Rujun Teng
Objective:
Edmund Luo
To assess the 54-week efficacy and safety of initial combination therapy with sitagliptin and metformin in
patients with type 2 diabetes and inadequate glycemic control (HbA
Michael J. Davies
1c
7.5–11%) on diet and exercise.
Keith D. Kaufman
Barry J. Goldstein
Methods and materials:
John M. Amatruda
This was multinational study conducted at 140 clinical sites in 18 countries. Following an initial 24-week,
double-blind, placebo-controlled period, patients entered a double-blind continuation period for an
Merck Research Laboratories, Rahway, NJ, USA
additional 30 weeks. Following the week 24
ed users can download
evaluation, patients remained on their previously assigned
active, oral treatments: sitagliptin 50 mg b.i.d.þmetformin 1000 mg b.i.d. (S100þM2000), sitagliptin
Address for correspondence: 50 mg b.i.d.þmetformin 500 mg
thoris
b.i.d. (S100þM1000), metformin 1000 mg b.i.d. (M2000), metformin
Debora Williams-Herman, MD, Merck Research
500 mg b.i.d. (M1000), and sitagliptin 100le copy for personal use mg q.d. (S100). Patients initially randomized to placebo were
Laboratories, RY34-A232, Rahway, NJ 07065, USA.
switched to M2000 (designated PBO/M2000) at week 24. This report summarizes the overall safety and
debora_williamsherman@merck.com
tolerability data for the 54-week study and presents efficacy results for patients randomized to continuous
treatments who entered the 30-week continuation period.
Key words:
n
t a sing
dipeptidyl peptidase-4 inhibitors – DPP-IV –
Results:
Incretins – MK-0431
Of the 1091 randomized patients, 906 completed the 24-week placebo-controlled phase and 885 patients
Accepted: 19 December 2008; published online: 15 January 2009 continued into the 30-week continuation period (S100þM2000 n¼161, S100þM1000 n¼160, M2000
Copyright © 2009 Informa UK Limited
n¼153, M1000 n¼147, S100 n¼141, PBO/M2000 n¼123). At baseline, patients included in the
efficacy analysis had mean age of 54 years, mean BMI of 32 kg/m
2
, mean HbA
1c
of 8.7% (8.5–8.8% across
Not for Sale or Commercial Distribution
groups), and mean duration of type 2 diabetes of 4 years. At week 54, in the all-patients-treated analysis of
continuing patients, least-squares (LS) mean changes in HbA
1c
from baseline were C01.8%
(S100þM2000), C01.4% (S100þM1000), C01.3% (M2000), C01.0% (M1000), and C00.8% (S100).
Unauthorized use prohibited. Au
display, view and pri
The proportions of continuing patients with an HbA
1c
57% at week 54 were 67% (S100þM2000),
48% (S100þM1000), 44% (M2000), 25% (M1000), and 23% (S100). For the patients completing
treatment through week 54, LS mean changes in HbA
1c
from baseline were C01.9% (S100þM2000),
C01.7% (S100þM1000), C01.6% (M2000), C01.2% (M1000), and C01.4% (S100). Glycemic response was
generally durable over time across treatments. All treatments improved measures of C12-cell function (e.g.,
HOMA-C12, proinsulin/insulin ratio). Mean body weight decreased from baseline in the combination and
metformin monotherapy groups and was unchanged from baseline in the sitagliptin monotherapy group.
The incidence of hypoglycemia was low (1–3%) across treatment groups. The incidence of gastrointestinal
adverse experiences with the co-administration of sitagliptin and metformin was similar to that observed
with metformin alone.
Limitations:
The patient population evaluated in the 54-week efficacy analysis was a population of patients who entered
the continuation period without receiving glycemic rescue therapy in the 24-week placebo-controlled period.
Because the baseline HbA
1c
inclusion criteria ranged from 7.5 to 11% and the glycemic rescue criterion was
an HbA
1c
48% after week 24, there was a greater likelihood of glycemic rescue in the monotherapy groups;
!
2009 Informa UK Ltd www.cmrojournal.com 54-week efficacy and safety of sitagliptin/metformin Williams-Herman et al.
1
Page 1  |  Page 2  |  Page 3  |  Page 4  |  Page 5  |  Page 6  |  Page 7  |  Page 8  |  Page 9  |  Page 10  |  Page 11  |  Page 12  |  Page 13  |  Page 14  |  Page 15  |  Page 16  |  Page 17  |  Page 18  |  Page 19  |  Page 20  |  Page 21  |  Page 22  |  Page 23  |  Page 24  |  Page 25  |  Page 26  |  Page 27  |  Page 28  |  Page 29  |  Page 30  |  Page 31  |  Page 32  |  Page 33  |  Page 34