Uploaded by User57609

khaloo2018-dikonversi

advertisement
Journal of Endocrinological Investigation
https://doi.org/10.1007/s40618-018-0991-0
ORIGINAL ARTICLE
Sitagliptin vs. pioglitazone as add‑ on treatments in patients
with uncontrolled type 2 diabetes on the maximal dose of metformin
plus sulfonylurea
P. Khaloo1 · S. Asadi Komeleh1 · H. Alemi1 · M. A. Mansournia2 · A. Mohammadi1 · A. Yadegar1 · M. Afarideh1 ·
S. Esteghamati1 · M. Nakhjavani1 · A. Esteghamati1
Received: 23 June 2018 / Accepted: 27 November 2018
© Italian Society of Endocrinology (SIE) 2018
Abstract
Aims To compare the efficacy of sitagliptin versus pioglitazone as add-on drugs in patients with poorly controlled diabetes
with metformin and sulfonylureas.
Methods This is a randomized, open-label, parallel assignment clinical trial. Patients who had inadequate glycemic
control [7% (53 mmol/mol) ≤ A1C < 11% (97 mmol/mol)] despite a minimum 6-month period of active treatment with
metformin 2000 mg/day plus gliclazide 240 mg/day were enrolled in the study. HbA1C, fasting blood glucose (FBG),
fasting plasma lipid parameters [total cholesterol (TC0, low-density lipoprotein cholesterol (LDL-C), triglycerides (TG)
and high-density lipoprotein cholesterol (HDL-C)], systolic and diastolic blood pressure (SBP, DBP), weight, waist
circumference, and body mass index were measured at baseline and after 17, 34, and 52 weeks of treatment. Generalized
estimating equation analysis was done to compare treatment groups for continuous efficacy parameters.
Results No significant difference in HbA1C reduction was observed between the treatment groups during the study
course. (P = 0.149, adjusted P = 0.434; coefficient − 0.11 ± 0.08). The FBG (P = 0.032; coefficient 7.44 ± 3.48), HDL-C (P =
0.001;
coefficient − 2.69 ± 0.83), TG (P = 0.027; coefficient 12.63 ± 5.71) and SBP (P < 0.001; coefficient 5.43 ± 1.26) changes from
baseline, and weight gain were greater in the pioglitazone group. The mean changes in LDL-C and TC from baseline to week
52 were greater in the sitagliptin group (P = 0.034; coefficient − 7.40 ± 3.50, P = 0.013; coefficient − 7.16 ± 2.88, respectively).
Conclusion Sitagliptin and pioglitazone were equally effective in improvement of HbA1C. There were some differences
in terms of lipid indices, weight gain, and SBP. The current study confirmed that both sitagliptin and pioglitazone are
effective treatment options and the decision should be made for each individual based on the baseline characteristics.
Keywords Sitagliptin · Pioglitazone · Efficacy · Type2 diabetes
Introduction
The number of people with diabetes is rising as a result of
population growth, aging, urbanization, increased prevalence of obesity, and physical inactivity. It is estimated that
the number of patients with diabetes may rise from
 A. Esteghamati
[email protected]
1
Endocrinology and Metabolism Research Center (EMRC),
Vali-Asr Hospital, School of Medicine, Tehran University
of Medical Sciences, P.O. Box: 13145-784, Tehran, Iran
2
Department of Epidemiology and Biostatistics, School
of Public Health, Tehran University of Medical Sciences,
Tehran, Iran
424 million in 2017 to 629 million in 2045 [1]. Metformin
is the first line of treatment, while gliclazide is the most
common conventional second line used in controlling type
2 diabetes mellitus (T2DM) [2].
Sitagliptin, approved by FDA in 2006, is the first dipeptidyl peptidase-4 (DPP-4) inhibitor which acts by preventing
inactivation of incretin hormones glucagon-like peptide-1
(GLP-1) and glucose-dependent insulin tropic polypeptide
(GIP). Recently, sitagliptin has been proposed as an alternative for uncontrolled diabetes in patients who failed to
respond to either metformin or gliclazide. It has been shown
that sitagliptin helps in improving the glycemic control and
lipid profile in addition to reducing the blood pressure and
body weight simultaneously [3–7].
13
Journal of Endocrinological Investigation
Pioglitazone is a thiazolidinedione approved by FDA in
1999 that has been recommended as an alternative in patients
with diabetes treated with a combination of metformin and
sulfonylurea (SU) but having poor glycemic control. Pioglitazone improves blood glucose control by decreasing target tissues’ insulin resistance through activating peroxisome
proliferator-activated receptor-gamma (PPRA-gamma) [8].
Pioglitazone could also improve abnormal lipid profile by
acting on PPRA-alpha in T2DM. Notably, changes in liver
function tests, blood pressure, and body weight have been
also reported [9–11].
However, many patients still could not reach glycemic targets with metformin and gliclazide and require other agents
in combination to control blood glucose level [12]. Numerous clinical trials have been done to show the efficacy and
safety of pioglitazone and sitagliptin as monotherapies or in
combination with other antidiabetic drugs as dual therapies
[13–15]. However, few trials have compared triple therapies
consisting each of these two oral agents with metformin and
gliclazide so far. A 24-week study has shown that pioglitazone and sitagliptin achieved similar improvements in overall glycemic control in patients inadequately controlled with
metformin and an SU, but there were some differences in
FBG, lipids, and body weight changes [16]. The durability of
these drugs is also of great importance. Both sitagliptin and
pioglitazone have been reported to have long-term effects on
glycemic control and improve durability when given in combination with other oral agents [17–19]. Therefore, in the
current study, we investigated the improvement in glycemic
control variables, lipid profile indices, blood pressure, and
weight control after adding sitagliptin or pioglitazone to conventional oral therapy (metformin + gliclazide) to compare
the efficacy and safety of these two drug regimens through
the 52 weeks of follow-up.
Materials and methods
Study population
Men and women with type 2 diabetes mellitus based on the
American Diabetes Association (ADA) criteria who had
inadequate glycemic control were enrolled in this study.
Their treatment regimen included a minimum 6 months
period of active treatment with the maximum dose of metformin, 2000 mg/day (500 mg QID) [20], plus the advised
maximum dose of gliclazide, 240 mg/day (80 mg TDS) [21].
Inadequate glycemic control was defined as baseline level of
7% (53 mmol/mol) ≤ A1C < 11% (97 mmol/mol).
Eligible patients were aged 25–70 years.
The following exclusion criteria were applied: cardiovascular disease (including myocardial infarction,
unstable angina, history of revascularization procedure
13
or cerebrovascular accident) or uncontrolled hypertension, estimated glomerular filtration rate (eGFR) < 60 ml/
min/1.73 m2 (calculated using the CKD–EPI equation),
treatment with corticosteroids or other drugs interfering
with glucose metabolism, any history of malignant disease,
active infectious disease or history of infectious disease in
the last 6 months, and a documented diagnosis of interstitial
or obstructive lung disease.
Study design
This is a randomized, open-label, parallel assignment clinical trial conducted in the diabetes clinic of Vali-Asr Hospital, affiliated to Tehran University of Medical Sciences
in Tehran, Iran. The study was performed between February 2015 and April 2017. Eligible patients were randomly
divided into two 1.1 ratio treatment groups by the use of
randomizations software. One took sitagliptin 100 mg daily,
and the other took pioglitazone 30 mg daily both in combination with metformin 500 mg QID and gliclazide 80 mg
TDS for 52 weeks. Patients were instructed to continue the
lifestyle they had prior to entry to the trial through these
52 weeks. Participants were withdrawn from the study if
they met any severe adverse effects including hypoglycemia,
heart failure, or hepatic failure. Prior to enrollment, written informed consents were taken from all participants. The
study was conducted in accordance with the Declaration of
Helsinki, and the Ethics Committee of the Tehran University
of Medical Sciences approved the study protocol. This trial
was registered with ClinicalTrials.gov (NCT03125694).
Study end point
The primary outcome of this study was a change in the
mean glycated hemoglobin (A1C) levels from baseline by
sitagliptin vs. pioglitazone during the 52 weeks of treatment. HbA1C, fasting blood glucose, fasting plasma lipid
parameters [total cholesterol (TC), low-density lipoprotein
cholesterol (LDL-C), triglycerides (TG) and high-density
lipoprotein cholesterol (HDL-C)], systolic and diastolic
blood pressure (SBP and DBP), weight, waist circumference
(WC), hip circumference (HC),and body mass index (BMI)
were measured at baseline and after 17, 34, and 52 weeks
of treatment. Secondary efficacy end points were changes in
HbA1C of patients who achieve the HbA1C < 7% (53 mmol/
mol), HbA1C < 6.5% (48 mmol/mol), and changes in other
previously mentioned measurements at week 17, 34, and 52.
Statistical analysis
Intent-to-treat (ITT) analysis was done using all randomized participants who received at least one dose of study
treatment, had baseline measurements of HbA1C,
Journal of Endocrinological Investigation
and at least one follow-up visit after initiation of treatment. Mean ± standard deviation (SD) for continuous and
frequencies (%) for categorical variables were used to
show the baseline characteristics of participants. Regression models with generalized estimating equation (GEE)
analysis were done to compare treatment groups for continuous efficacy parameters, taking into account the correlation between repeated variable measurements of the
same subjects. Treatments as indicator variables were the
main predictors of the model. In the model, the variable
“time” was defined as months from the baseline visit. In
our study, univariable regression analysis was per- formed
for each potential risk factor including age, sex, duration of
diabetes, weight, waist circumference, BMI, SBP, DBP,
HbA1C, FBG, and lipid profile. Later on, covariates with a
P value < 0.2 in the initial univariable analysis were
selected to enter the multivariable model. Age, sex, weight,
duration of diabetes, time, HbA1C, and baseline values
were entered in the final model as covariates. The
interaction between time and treatment was examined in
the multivariate model. Considering that there was no
significant interaction, we did not enter their product term
in regression models with the generalized estimating
equation. Missing data were han- dled using the lastobservation-carried-forward method. We used Huber-white
cluster robust standard error for calculating 95%
confidence interval. The proportion of patients achieving
HbA1C ≤ 7 (53) or ≤ 6.5% (48 mmol/ mol) was compared
among groups using logistic regres- sion analysis.
Statistical analyses were performed using STATA version
12; P values ≤ 0.05 were considered sta- tistically
significant.
Results
Baseline characteristics
A total of 250 participants were recruited. 125 patients were
randomized in each treatment group. One hundred and ten
patients with the mean age of 62.7 in the pioglitazone group
and 112 patients with the mean age of 60.8 in the sitagliptin
group completed the 52 weeks of treatment including 128
females and 94 males. The factors leading to early study
discontinuation were weight gain (nine in the pioglitazone
group), edema (six in the pioglitazone group), GI upset (five
in the sitagliptin group),and cost consideration (8 in the sitagliptin group) (Fig. 1). Percentage of females and duration
of diabetes were significantly higher in patients randomly
assigned to the pioglitazone group at baseline. Additionally, SBP and weight were higher in the sitagliptin group.
Randomized and treated
(N=250)
Sitagliptin 100mg
(N=125)
Pioglitazone 30mg
(N=125)
Discontinued study
(N=13)
GI upset
5
Cost consideration 8
Discontinued study
(N=15)
Weight gain
9
Edema
6
Completed 52 weeks
(N=112)
Completed 52 weeks
(N=110)
Fig. 1 Study population flowgram
Table 1 Baseline characteristics and demographics of randomized
patients
Pioglitazone
Sitagliptin
P value
Sex
Female
Male
Age
DM Duration
Weight
BMI
WC
HC
SBP
DBP
FBG
TC
HDL-C
LDL-C
TG
71 (55.5%)
39 (41.5%)
62.7 ± 8.2
14.3 ± 6.9
74.2 ± 13.5
29 ± 4.8
107.2 ± 85.9
104.3 ± 9.3
129.1 ± 14.1
79.4 ± 6.1
180.2 ± 47.5
167 ± 32.8
43.2 ± 10.6
90.4 ± 25.6
169 ± 70
57 (44.5%)
55 (58.5%)
60.8 ± 8.1
11.3 ± 6.2
78.3 ± 12.5
29.7 ± 4.3
101.6 ± 10
106.5 ± 9.9
135.7 ± 16.2
78.8 ± 8.2
171.4 ± 44.1
158.1 ± 34.6
42.3 ± 9
87.9 ± 26.8
150.2 ± 75.3
0.04
N/S
0.001
0.019
N/S
N/S
N/S
0.001
N/S
N/S
N/S
N/S
N/S
N/S
HbA1C
9 ± 1.2
8.8 ± 1.1
N/S
DM diabetes, SBP systolic blood pressure, DBP diastolic blood pressure, BMI body mass index, WC waist circumferences, HC hip circumference, FPG fasting plasma glucose, TC total cholesterol, TG
triglyceride, HDL-C high-density lipoprotein cholesterol, LDL-C lowdensity lipoprotein cholesterol
There was no significant difference in other baseline measurements and clinical characteristics of the two treatment
groups (Table 1).
13
Journal of Endocrinological Investigation
Fig. 2 HBA1C levels over time up to 52 weeks of treatment
The mean changes in LDL-C and TC from baseline to week 52 were greater in the sitagliptin group
(P = 0.034; coefficient − 7.40 ± 3.50, P = 0.013; coefficient
− 7.16 ± 2.88, respectively). On the other hand, the mean
changes observed during 52 weeks in HDL-C and TG were
significantly higher in the pioglitazone group (P = 0.001;
coefficient − 2.69 ± 0.83, P = 0.027; coefficient 12.63 ± 5.71,
respectively).
At week 52, a decrease in body weight and HC with sitagliptin and an increase with pioglitazone were observed
which led to a significant difference between the two treatment groups (P < 0.001; coefficient − 2.44 ± 0.34, P < 0.001;
coefficient − 1.68 ± 0.45, respectively).
SBP increased during the study course in both sitagliptin (3 ± 15.4) and pioglitazone (2.4 ± 14.6) groups, but the
changes in the sitagliptin group were significantly greater
(P < 0.001; coefficient 5.43 ± 1.26). DBP changes were not
different between the two treatment groups (P = 0.161). No
subjects showed any clinically significant adverse events.
Changes in all study end points during the follow-ups are
shown in Table 2.
Discussion
Fig. 3 FBG changes over time up to 52 weeks of treatment
Efficacy
The mean HbA1C changes from baseline to week 52 were
− 1.9 ± 1.2% for the pioglitazone group and − 1.8 ± 1% for
the sitagliptin group, but no significant difference in HbA1C
reduction was observed between the treatment groups during
the study course (P = 0.149, adjusted P = 0.434; coefficient
− 0.11 ± 0.08). HbA1C values over time up to 52 weeks
are shown in Fig. 2. After 52 weeks of treatment, the percentage of participants reaching the HbA1C goal of < 7%
(53 mmol/mol) was significantly higher in the pioglitazone
group (57.3%) compared to the sitagliptin group (42.7%)
(Adjusted P = 0.048; IRR 1.31 ± 0.18). However, no difference was seen between the treatment groups (P = 0.139) by
changing the target definition to HbA1C < 6.5% (48 mmol/
mol).
Both pioglitazone and sitagliptin decreased FBG during
the study course (− 45 ± 52, − 35 ± 46.4 mg/dL, respectively), but the FBG changes from baseline were greater in
the pioglitazone group (P = 0.032; coefficient 7.44 ± 3.48).
Figure 3 shows the FBG values over time up to week 52.
13
While metformin is widely recognized as the first line of
diabetes treatment, physicians should choose the second and
third line of antidiabetic agents according to the patients’
baseline characteristics and glycemic control, suggested by
international and national guidelines. There is no consensus
about how to intensify treatment in patients with poor glycemic control [22]. Here, we compared the efficacy of sitagliptin and pioglitazone as add-on drugs in triple therapy with
metformin and SU. We found that although adding sitagliptin or pioglitazone both result in better glycemic control,
there was no significant difference in HbA1C improvement
between these two drug regimens after 52 weeks of treatment. However, pioglitazone was more potent in reaching
HbA1C target goal [HbA1C < 7% (53 mmol/mol)]. Our
results also showed a greater change in FBG with pioglitazone despite the similar effect on HbA1C.
Significant reductions in HbA1C, FBG, and postprandial plasma glucose have been shown in previous studies
using pioglitazone and sitagliptin alone or in combination
with other treatments in patients with T2DM. The observed
effects of pioglitazone and sitagliptin on HbA1c in the current study are similar to those reported in previous clinical
studies [23]. In Kutoh et al.’s study, significant changes of
HbA1c (from 10.05 to 8.01%) were observed in drug-naïve
Japanese patients with diabetes [24]. Pioglitazone was indicated to be as effective as metformin elsewhere [25]. Pioglitazone and sitagliptin are also considered to be effective in
patients with poor glycemic control using metformin alone
Journal of Endocrinological Investigation
Table 2 Changes of clinical
data from baseline during
treatment with sitagliptin or
pioglitazone
Week 17
Pioglitazone
Week 34
Sitagliptin
Pioglitazone
Week 52
Sitagliptin
Pioglitazone
Weight (kg)*
0.4 ± 1.1
− 0.1 ± 0.8
0.7 ± 1.3 − 0.2 ± 0.9
0.9 ± 1.5
BMI (kg/m2)
1 ± 2.8
− 0.4 ± 2
1.9 ± 3.3 − 0.6 ± 2.4
2.3 ± 3.8
WC (cm)
− 7.6 ± 85.7
− 0.3 ± 3.5
− 6.8 ± 85.8 − 0.4 ± 4.2
− 6.6 ± 85.8
HC (cm)*
1.1 ± 3
− 0.5 ± 2.9
1.6 ± 4.9
− 1 ± 3.5
2 ± 5.3
FBG (mg/dL)*
− 42 ± 47.7 − 30.3 ± 45.3 − 41.4 ± 52.8 − 31 ± 43.8
− 45 ± 52
HbA1C (%)
− 1.3 ± 1.1
− 1.1 ± 0.9
− 1.6 ± 1.2
− 1.5 ± 1
− 1.9 ± 1.2
TG (mg/dL)*
− 28.1 ± 56.6
− 4.1 ± 56.5 − 21.1 ± 62.9
4.2 ± 64.3 − 22.9 ± 58.6
TC (mg/dL)*
− 1.7 ± 27.9
− 7.3 ± 29.4
− 3.1 ± 33.2 − 4.7 ± 31.1
− 3.4 ± 33.7
HDL-C (mg/dL)*
2.4 ± 7
− 0.7 ± 7.8
2.7 ± 7.9 − 0.2 ± 8.2
3.2 ± 10.1
LDL-C (mg/dL)*
8 ± 93.1 − 5.6 ± 23.3
− 0.6 ± 28.4 − 3.2 ± 26.6
− 0.9 ± 29.1
SBP (mmHg)*
− 2.1 ± 12
1.5 ± 13.3
0.6 ± 12.7
1.6 ± 15.7
2.4 ± 14.6
DBP (mmHg)
− 1.7 ± 6.3
− 1.8 ± 7.9
− 0.3 ± 7.4
− 1.4 ± 9.1
− 0.6 ± 7.8
Sitagliptin
− 0.5 ± 1.1
− 1.2 ± 2.8
− 0.1 ± 4.3
− 0.7 ± 3.1
− 35 ± 46.4
− 1.8 ± 1
− 1.7 ± 65.3
− 6.9 ± 34.6
1 ± 9.6
− 6 ± 27.5
3 ± 15.4
− 0.6 ± 8.9
DM diabetes, SBP systolic blood pressure, DBP diastolic blood pressure, BMI body mass index, WC waist
circumferences, HC hip circumference, FPG fasting plasma glucose, TC total cholesterol, TG triglyceride,
HDL-C high-density lipoprotein cholesterol, LDL-C low-density lipoprotein cholesterol
*Refers to significant difference between two treatment groups during the study course
or metformin in combination with SU [6, 26]. Nevertheless, there are not adequate data to decide which one is the
preferred alternative to intensify the metformin and SU dual
therapy. In concordance with our results, Sung-Chen et al.’s
study showed a similar HbA1C reduction using pioglitazone and sitagliptin in patients with T2DM inadequately
controlled with metformin and an SU. They also showed a
greater FBG change in the pioglitazone group which was in
favor of our results [16].
The desirable effect of pioglitazone and sitagliptin on
lipid profile is well established. Sitagliptin is known to be
effective on all lipid components [24, 25], while the effect
of pioglitazone is mainly limited to TG and HDL-C [23, 27,
28]. Moreover, a recent meta-analysis indicated that sitagliptin is also more beneficial in the improvement of serum
TG and HDL-C levels, especially when used in combination with other treatments [29]. Our results extended the
present data and showed a positive effect on TG, HDL-C,
LDL-C, and TC for both sitagliptin and pioglitazone when
added to dual therapy with metformin and SU. Furthermore,
we observed that improvements in HDL-C and TG were
significantly greater with pioglitazone, while changes in
TC and LDL-C were in favor of sitagliptin. In Sung-Chen
et al.’s study, the only prominent improvement observed in
the pioglitazone group was on TG and HDL-C with no significant difference in other lipid components [16]. It can be
deduced that serum levels of lipid parameters are important
factors for choosing the third line of treatment.
In agreement with the established effect of pioglitazone
on body weight [24, 30], we found a significant increase
in HC and body weight with pioglitazone during the study
course. On the contrary to the ADA/EASD statement [31]
on the neutral effect of sitagliptin on weight gain, a significant decrease in body weight and HC was observed in our
study. These results led to a significant difference in body
weight and HC between the two groups of treatment in favor
of sitagliptin. Weight gain resulted in early discontinuation
of pioglitazone in nine patients and peripheral edema led to
drug withdrawal in six patients in the pioglitazone group,
whereas discontinuation in the sitagliptin group was mainly
because of cost consideration. Although both drugs were
well tolerated during the study and no adverse events were
reported, taking all the observations into account, sitagliptin
was a better choice according to the side effects in our study.
Cardiovascular safety is another noticeable element in
diabetes therapy, considering the high risk of cardiovascular events among these patients. Presently, the effect of
sitagliptin on blood pressure remains controversial. Some
studies indicate an improvement in the blood pressure [32,
33], while others report that sitagliptin either increases the
blood pressure [34] or does not affect it [35]. In contrast,
literature mostly indicates favorable effects on BP for pioglitazone [36, 37]. In our study, SBP increased in both pioglitazone and sitagliptin groups and the change was greater
with pioglitazone. Our results showed no difference regarding DBP between the two groups. Our results confirmed the
context-dependent effect of sitagliptin on BP, which could
be due to the complex modification in the levels of biologically active peptides that would accompany the inhibition of
DPP4 [38]. The observed discrepancy for pioglitazone can
be due to racial differences, since it is reported that different
ethnicities in different regions or even same geographical
regions have different outcomes and drug responses to the
same endocrine disease [39, 40].
13
Journal of Endocrinological Investigation
Glycemic durability of sitagliptin and pioglitazone as
monotherapies or in combination with other drugs was
reported in 4–5 years follow-up studies which all indicated the long-term effect of these two drugs [18, 19].
Ching-Jung et al. showed that in the initial 6 months of
sitagliptin therapy, the HbA1C concentration was reduced
significantly, but the HbA1C levels fluctuated mildly, followed by a 0.1% increase from 6 to 48 months of therapy
[41]. Another trial stated that sitagliptin was effective in
patients with suboptimal glycemic control with metformin,
SU or dual therapy, maximum between 36 and 48 weeks
[42]. Besides, it was found that pioglitazone could result in
improved glycemic durability when given in combina- tion
with other oral glucose-lowering drugs compared with oral
glucose-lowering treatment alone [17]. Considering the
drugs’ durability and the fact that present data on the
comparison of pioglitazone and sitagliptin efficacy in triple therapy is limited to one 28 weeks length study [16],
we decided to follow patients for 52 weeks. We found that
HbA1C and FBG decreased in both groups after 4 months
and the glucose-lowering effect was maintained through all
the follow-ups up to 52 weeks. We did not observe any
time–treatment interaction for both sitagliptin and pioglitazone, and no difference in glycemic durability between
the two groups was seen.
There are several limitations in our study. We did not
have a control group, so the changes observed in glycemic
or lipid indices in each group from baseline can be due to
the placebo effect. However, the main question of the study
is to compare pioglitazone and sitagliptin in a triple therapy
which is not affected by this limitation. Additionally, we
did not have any data about the patients’ physical activity
and diet. These two factors could both modify the evaluated
variables. Hence, to minimize the potential effects of these
factors, patients were given a diet plan, and they were asked
to continue the lifestyle they had prior to entry to the trial
through the 52 weeks of the study. Moreover, there were
slight differences in the baseline characteristics of the two
treatment groups, which might have affected the obtained
results. All the potential confounders including the whole
baseline demographic and measurements were considered
in our analysis to minimize the possible effect of basal differences of the two cohorts studied.
In conclusion, sitagliptin and pioglitazone were equally
effective in improvement of HbA1C. Pioglitazone was superior in reducing the FBG compared to sitagliptin. There were
also some differences regarding body weight and SBP in
favor of sitagliptin. In the case of lipid control indices, TG
and HDL-C were better controlled with pioglitazone, while
TC and LDL-C had greater improvement with sitagliptin.
The current study confirmed that both sitagliptin and pioglitazone are effective treatment options in patients treated
with metformin and SU who require more intensive therapy.
13
This decision should be made separately for each individual
based on the baseline characteristics.
Acknowledgements The authors wish to thank the patients for their
participation and kind cooperation.
Funding This research did not receive any specific grant from
funding agencies in the public, commercial, or not-for-profit sectors.
Data availability All data generated or analyzed during this study are
included in this submitted article.
Compliance with ethical standards
Conflict of interest The authors declare that they have no competing
interest.
Ethical approval All procedures performed in studies involving
human participants were in accordance with the ethical standards of
the insti- tutional and/or national research committee and with the 1964
Helsinki Declaration and its later amendments or comparable ethical
standards.
Informed consent Informed consent was obtained from all
individual participants included in the study.
References
1. Ogurtsova K et al (2017) IDF diabetes atlas: global estimates for
the prevalence of diabetes for 2015 and 2040. Diabetes Res Clin
Pract 128:40–50
2. 2 Diabetes. 2013 Sep. https://www.ncbi.nlm.nih.gov/books/
NBK361996/, C.R.P.i.B.I.O.O.C.A.f.D.a.T.i.H.-O.S.-a.T.-L.T.i.T
3. Ahren B (2010) Use of DPP-4 inhibitors in type 2 diabetes: focus
on sitagliptin. Diabetes Metab Syndr Obes 3:31–41
4. Drucker DJ, Nauck MA (2006) The incretin system: glucagon-like
peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors
in type 2 diabetes. Lancet 368(9548):1696–1705
5. Derosa G et al (2014) Sitagliptin added to previously taken antidiabetic agents on insulin resistance and lipid profile: a 2-year
study evaluation. Fundam Clin Pharmacol 28(2):221–229
6. Ba J et al (2017) Randomized trial assessing the safety and efficacy of sitagliptin in Chinese patients with type 2 diabetes mellitus inadequately controlled on sulfonylurea alone or combined
with metformin. J Diabetes 9(7):667–676
7. Harashima SI et al (2012) Sitagliptin add-on to low dosage sulphonylureas: efficacy and safety of combination therapy on glycaemic
control and insulin secretion capacity in type 2 diabetes. Int J Clin
Pract 66(5):465–476
8. Smith U (2001) Pioglitazone: mechanism of action. Int J Clin
Pract Suppl 121:13–18
9. Al-Azzam SI et al (2012) Effects of pioglitazone add-on to gliclazide and metformin on glycemic control in patients with type
2 diabetes. Endocr Res 37(1):7–11
10. Filipova E et al (2017) Effects of pioglitazone therapy on blood
parameters, weight and BMI: a meta-analysis. Diabetol Metab
Syndr 9(1):90
11. Hirose H et al (2002) Effects of pioglitazone on metabolic
parameters, body fat distribution, and serum adiponectin levels
in Japanese male patients with type 2 diabetes. Metab Clin Exp
51(3):314–317
Journal of Endocrinological Investigation
12. Turner RC et al (1999) Glycemic control with diet, sulfonylurea,
metformin, or insulin in patients with type 2 diabetes mellitus:
progressive requirement for multiple therapies (UKPDS 49).
JAMA 281(21):2005–2012
13. Sharma M et al (2017) Effectiveness of sitagliptin compared to
sulfonylureas for type 2 diabetes mellitus inadequately controlled
on metformin: a systematic review and meta-analysis. BMJ Open
7(10):e017260
14. Nauck M et al (2014) Efficacy and safety of dulaglutide versus
sitagliptin after 52 weeks in type 2 diabetes in a randomized controlled trial (AWARD-5). Diabetes Care 37(8):2149–2158
15. Herz M et al (2003) A randomized, double-blind, placebocontrolled, clinical trial of the effects of pioglitazone on glycemic control and dyslipidemia in oral antihyperglycemic medication-naive patients with type 2 diabetes mellitus. Clin Ther
25(4):1074–1095
16. Liu SC et al (2013) Efficacy and safety of adding pioglitazone or
sitagliptin to patients with type 2 diabetes insufficiently controlled
with metformin and a sulfonylurea. Endocr Pract 19(6):980–988
17. Stringer F et al (2015) Evaluation of the long-term durability
and glycemic control of fasting plasma glucose and glycosylated
hemoglobin for pioglitazone in Japanese patients with type 2 diabetes. Diabetes Technol Ther 17(3):215–223
18. Ku EJ et al (2015) Four-Year durability of initial combination therapy with sitagliptin and metformin in patients with type 2 diabetes
in clinical practice; COSMIC study. PLoS one 10(6):e0129477
19. Derosa G, D’Angelo A, Maffioli P (2015) Sitagliptin in type 2
diabetes mellitus: efficacy after 5 years of therapy. Pharmacol Res
100:127–134
20. International Diabetes Federation. Recommendations for managing type 2 diabetes in primary care, 2017. http://www.idf.org/
managing-type2-diabetes. Accessed 20 Aug 2018
21. Landman GW et al (2014) Safety and efficacy of gliclazide as
treatment for type 2 diabetes: a systematic review and meta-analysis of randomized trials. PLoS One 9(2):e82880
22. Aschner P, Beck-Nielsen H, Bennett P, Boulton A, Colagiuri R,
Colagiuri S, Franz M, Gadsby R, Gagliardino JJ, Home P, McGill
M, Manley S, Marshall S, Mbanya JC, Neil A, Ramachandran
A, Ramaiya K, Roglic G, Schaper N, Siminerio L, Sinclair A,
Snoek F, Van Crombrugge P, Vespasiani G, Viswanathan V, Sim
K (2014) Global guideline for type 2 diabetes. Diabetes Res Clin
Pract 104(1):1–52
23. Ikeda H, Sugiyama Y (2001) Pharmacological effects of a
thiazolidinedione derivative, pioglitazone. Nihon Rinsho
59(11):2191–2194
24. Kutoh E (2010) Differential effects of pioglitazone on metabolic
parameters in newly diagnosed, drug-naive Japanese patients with
type 2 diabetes with or without metabolic syndrome. Endocr Res
35(3):118–127
25. Erem C et al (2014) Comparison of effects of gliclazide, metformin and pioglitazone monotherapies on glycemic control
and cardiovascular risk factors in patients with newly diagnosed
uncontrolled type 2 diabetes mellitus. Exp Clin Endocrinol Diabetes 122(5):295–302
26. Moses RG et al (2016) A randomized clinical trial evaluating the
safety and efficacy of sitagliptin added to the combination of sulfonylurea and metformin in patients with type 2 diabetes mellitus
and inadequate glycemic control. J Diabetes 8(5):701–711
27. Baba S (2001) Pioglitazone: a review of Japanese clinical studies.
Curr Med Res Opin 17(3):166–189
28. Lu ZH et al (2011) A randomized, double blind, placebo-controlled, parallel and multicenter study to evaluate the safety and
efficacy of pioglitazone with sulphonylurea in type 2 diabetic
patients. Zhonghua Nei Ke Za Zhi 50(10):826–830
29. Fan M, Li Y, Zhang S (2016) Effects of sitagliptin on lipid Profiles in patients with type 2 diabetes mellitus: a meta-analysis of
randomized clinical trials. Med (Baltim) 95(2):e2386
30. Aghamohammadzadeh N et al (2015) The effect of pioglitazone
on weight, lipid profile and liver enzymes in type 2 diabetic
patients. Ther Adv Endocrinol Metab 6(2):56–60
31. Inzucchi SE et al (2012) Management of hyperglycemia in type
2 diabetes: a patient-centered approach: position statement of
the American diabetes association (ADA) and the European
association for the study of diabetes (EASD). Diabetes Care
35(6):1364–1379
32. Yuasa S et al (2017) Primary care-based investigation of the effect
of sitagliptin on blood pressure in hypertensive patients with type
2 diabetes. J Clin Med Res 9(3):188–192
33. Hussain M et al (2016) Effect of sitagliptin on glycemic control,
body weight, blood pressure and serum lipid profile in type 2
diabetic hyperlipidemic patients. J Ayub Med Coll Abbottabad
28(2):369–372
34. Jackson EK, Dubinion JH, Mi Z (2008) Effects of dipeptidyl peptidase iv inhibition on arterial blood pressure. Clin Exp Pharmacol
Physiol 35(1):29–34
35. Zhang X, Zhao Q (2016) Effects of dipeptidyl peptidase-4 inhibitors on blood pressure in patients with type 2 diabetes: a systematic review and meta-analysis. J Hypertens 34(2):167–175
36. Giles TD, Sander GE (2007) Effects of thiazolidinediones on
blood pressure. Curr Hypertens Rep 9(4):332–337
37. Takahashi A, Kushiro T (2008) Pioglitazone effects on blood
pressure in patients with metabolic syndrome. Nihon Rinsho
66(8):1591–1595
38. Jackson EK et al (2015) Effect of dipeptidyl peptidase 4 inhibition on arterial blood pressure is context dependent. Hypertension
65(1):238–249
39. Chong SA et al (2009) Depressive symptoms and diabetes mellitus
in an Asian multiracial population. Asian J Psychiatr 2(2):66–70
40. Golden SH et al (2012) Health disparities in endocrine disorders:
biological, clinical, and nonclinical factors–an Endocrine Society
scientific statement. J Clin Endocrinol Metab 97(9):E1579–E1639
41. Hsieh CJ, Shen FC (2014) The durability of sitagliptin in elderly
patients with type 2 diabetes. Clin Interv Aging 9:1905–1911
42. Mamza J et al (2015) Comparative efficacy of adding sitagliptin
to metformin, sulfonylurea or dual therapy: a propensity scoreweighted cohort study. Diabetes Ther 6(2):213–226
13
Download
Random flashcards
Rekening Agen Resmi De Nature Indonesia

9 Cards denaturerumahsehat

Nomor Rekening Asli Agen De Nature Indonesia

2 Cards denaturerumahsehat

Secuplik Kuliner Sepanjang Danau Babakan

2 Cards oauth2_google_2e219703-8a29-4353-9cf2-b8dae956302e

Create flashcards