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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
Table 1. Disposition of randomized patients over 54 weeks.
Screened N¼3544
Randomized n¼1091*
Placebo/metformin Sitagliptin Metformin Metformin Sitagliptin 50mg Sitagliptin 50mg
1000mg b.i.d. 100mg q.d. 500mg b.i.d. 1000mg b.i.d. b.i.d.þMF b.i.dþMF
500mg b.i.d. 1000mg b.i.d.
Randomized, n 176 179 182 182 190 182
Discontinued prior to 53 38 35 29 30 21
continuation phase, n
Entered continuation 123 141 147 153 160 161
phase
y
, n
Discontinued in 819211712 20
continuation phase, n
Reasons for discontinua
tions over 54 weeks
Clinical AE, n 9871 6 3
Laboratory AE, n 24200 2
Lack of efficacy
z
, n 14 11 14 7 4 3
Lost to follow-up, n 954 510
Other, n 54300 5
Moved, n 10112 3
Withdrew consent, n 15 17 16 16 15 10
Met protocol-specific 32526 5
discontinuation
criteria, n
Protocol deviation, n 36424 0
Completed, n (%) 115 (65) 122 (68) 126 (69) 136 (75) 148 (78) 141 (77)
*Disposition of patients not randomized published in Goldstein et al.
15
.
y
Includes patients who did and did not initiate glycemic rescue therapy in phase A.
z
Includes patients not meeting the progressively stricter protocol-specified glycemic criteria and/or not meeting the investigator’s expectations of glycemic
improvement.
MF, metformin.
co-administration,low-doseco-administration,metformin for high-dose co-administration, C096.2mg/dL (C0105.5,
1000mg b.i.d., metformin 500mg b.i.d., and sitagliptin C086.9; n¼98) for low-dose co-administration,
groups, respectively. C082.3mg/dL (C091.7, C072.9; n¼93) for metformin
In the CAPT population, FPG decreased relative to 1000mg b.i.d., C064.3mg/dL (C075.0, C053.5; n¼72) for
baseline at week 54 in all groups, with larger reductions metformin 500mg b.i.d., and C066.2mg/dL (C078.6,
observed in the co-administration groups compared with C053.8; n¼54) for sitagliptin.
their respective monotherapy groups (Table 3 and Measures ofC12-cell function, the proinsulin/insulin ratio
Figure 3). In the completers analysis, the LS mean FPG and HOMA-C12, were improved relative to baseline at week
changes from baseline wereC059.4mg/dL (95% CI:C064.8, 54 in all treatment groups, with larger improvement
C053.9; n¼123) for high-dose co-administration, observed in the co-administration groups relative to their
C049.8mg/dL (C055.7, C044.0; n¼109) for low-dose respective monotherapy groups (Table 3). HOMA-IR was
co-administration, C043.8mg/dL (C049.8, C037.8; n¼100) similarly reduced relative to baseline in the co-administra-
formetformin1000mgb.i.d.,C035.6mg/dL(C042.5,C028.7; tion groups compared with their respective metformin
n¼77) for metformin 500mg b.i.d., and C026.0mg/dL monotherapy group (Table 3).
(C034.0, C018.1; n¼58) for sitagliptin. Co-administration of sitagliptin and metformin gener-
Following a standard meal at week 54, 2-hour PPG, ally showed small numeric improvements compared with
total glucose AUC, and the ratio of insulin AUC to glu- baselineandcomparedwithoneorbothmonotherapiesfor
cose AUC were improved with all active treatments rela- TC, LDL-C, non-HDL-C, and triglycerides (Table 5).
tive to baseline in the CAPT population (Table 4). The Changes from baseline in HDL-C were similar between
changes in these parameters with co-administration the co-administration group and its respective metformin
were larger when compared with the sitagliptin and monotherapy group. Treatment with sitagliptin 100mg
respective metformin monotherapy groups. Total insulin q.d. had a generally neutral effect on lipids (Table 5).
and C-peptide AUCs were increased relative to baseline Similar within-group results were observed in the
with sitagliptin at week 54 (Table 4). In the completers 24-week placebo-controlled period (Table 6).
analysis, the LS mean 2-hour PPG changes from baseline After 54 weeks (CAPT population), body weight was
were C0111.1mg/dL (95% CI: C0119.6, C0102.5; n¼114) reduced relative to baseline in the co-administration
!
2009 Informa UK Ltd www.cmrojournal.com 54-week efficacy and safety of sitagliptin/metformin Williams-Herman et al.
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