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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 7. Summary of clinical adverse experiences through 54 weeks (APaT population).
Number (%) Placebo/ MF Sitagliptin Metformin Metformin Sitagliptin 50mg Sitagliptin 50mg
of patients* 1000mg b.i.d.
y
100mg q.d. 500mg b.i.d 1000mg b.i.d. b.i.dþMF b.i.d.þMF
N¼176 N¼179 N¼182 N¼182 500mg b.i.d. 1000mg b.i.d.
N¼190 N¼182
One or more AEs 97 (55) 105 (59) 114 (63) 129 (71) 130 (68) 126 (69)
Drug-related AEs
z
21 (12) 15 (8) 24 (13) 32 (18) 29 (15) 34 (19)
Serious AEs (SAEs) 13 (7) 12 (7) 6 (3) 3 (2) 7 (4) 7 (4)
Drug-related SAEs
z
1(51) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0)
Who died 1 (51) 0 (0) 0 (0) 0 (0) 0 (0) 1 (51)
Discontinued due to 9 (5) 5 (3) 6 (3) 7 (4) 6 (3) 4 (2)
AEs
Discontinued due to 2 (1) 0 (0) 2 (1) 5 (3) 3 (2) 2 (1)
drug-related AEs
Discontinued due to 7 (4) 4 (2) 4 (2) 1 (51) 1 (51) 0 (0)
SAEs
Discontinued due to 1(51) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0)
drug-related SAEs
Special AEs of Clinical
Interest
Hypoglycemia 4 (2) 2 (1) 2 (1) 2 (1) 4 (2) 5 (3)
All gastrointestinal 28 (16) 36 (20) 37 (20) 57 (31) 50 (26) 53 (29)
AEs
Selected gastroin
testinal AEs
Diarrhea 11 (6) 7 (4) 13 (7) 22 (12) 17 (9) 23 (13)
Nausea 4 (2) 2 (1) 6 (3) 18 (10) 10 (5) 11 (6)
Abdominal pain
x
5 (3) 8 (5) 7 (4) 10 (6) 5 (3) 7 (4)
Vomiting 1 (1) 1 (1) 0 (0) 6 (3) 4 (2) 7 (4)
*Excludes data after initiation of glycemic [glyburide/glibenclamide] rescue therapy.
y
Patients were switched from placebo to metformin 1000mg b.i.d. at week 24.
z
Considered by the investigator to be drug-related.
x
Including abdominal pain, abdominal discomfort, upper abdominal pain, and stomach discomfort.
MF, metformin, AE, adverse experiences.
All treatments were generally well tolerated for 54 in phase A, took at least one dose of study medication in
weeks. The additional 30 weeks of treatment extend and the continuation phase, and had at least one efficacy mea-
supportthefindingsreportedforthe24-weekplacebo-con- surement during the continuation phase. Second, because
trolled portion of this study
15
. Despite the substantial and the baseline HbA
1c
inclusion criteria ranged from 7.5 to
durable improvements in glycemic control observed with 11%andtheglycemicrescuecriterionwasanHbA
1c
48%
all active treatments, the incidence of hypoglycemia was
after week 24, there was a greater likelihood of glycemic
low and similar across the treatment groups over 54 weeks.
rescue in the monotherapy groups; thisled tomore missing
The incidences of overall and select gastrointestinal
data in the CAPT analysis and fewer patients contributing
adverse experiences were similar for the combination
to thecompleters analysis inthe monotherapy groups.The
and metformin monotherapy groups. Because some incre-
present study assesses the efficacy and safety of these treat-
tin-based therapies have been shown to have gastrointest-
ments for 54 weeks. This study has been extended for an
inal side-effects
17
, it is noteworthy that sitagliptin did not
additional 50weeks to further assess thesafety and efficacy
exacerbate the gastrointestinal side-effects commonly
of combination therapy with sitagliptin and metformin.
associated with metformin
28
, even when used as initial
therapy. The combination of sitagliptin and metformin
provided weight loss from baseline similar to that observed
with metformin monotherapy, whereas sitagliptin alone
Conclusions
was weight neutral over 54 weeks. This suggests that sita-
gliptindoesnotaffecttheweightlossusuallyobservedwith
In this study of patients with type 2 diabetes and
metformin
28
. inadequate glycemic control on diet and exercise, therapy
Thisstudyhadsomelimitations.First,thepatientpopu- withsitagliptin,metformin,orthecombinationofsitaglip-
lation evaluated was not a randomized population in that tin and metformin provided substantial and durable glyce-
this study evaluated randomized patients who had a base- mic control, improved markers of C12-cell function, and was
line measurement, did not receive glycemic rescue therapy generally well-tolerated over 54 weeks.
!
2009 Informa UK Ltd
www.cmrojournal.com 54-week efficacy and safety of sitagliptin/metformin Williams-Herman et al.
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