Transcript 20131003AlogliptinACS&ChinaDM

Journal Club
White WB, Cannon CP, Heller SR, Nissen SE, Bergenstal RM, Bakris GL, Perez AT,
Fleck PR, Mehta CR, Kupfer S, Wilson C, Cushman WC, Zannad F; the EXAMINE
Investigators.
Alogliptin after Acute Coronary Syndrome in Patients with Type 2 Diabetes.
N Engl J Med. 2013 Sep 2. [Epub ahead of print]
Xu Y, Wang L, He J, Bi Y, Li M, Wang T, Wang L, Jiang Y, Dai M, Lu J, Xu M, Li Y,
Hu N, Li J, Mi S, Chen CS, Li G, Mu Y, Zhao J, Kong L, Chen J, Lai S, Wang W,
Zhao W, Ning G; 2010 China Noncommunicable Disease Surveillance Group.
Prevalence and control of diabetes in Chinese adults.
JAMA. 2013 Sep 4;310(9):948-59. doi: 10.1001/jama.2013.168118.
2013年10月3日 8:30-8:55
８階 医局
埼玉医科大学 総合医療センター 内分泌・糖尿病内科
Department of Endocrinology and Diabetes,
Saitama Medical Center, Saitama Medical University
松田 昌文 坂下 杏奈
Matsuda, Masafumi, Sakashita, Anna
DPP-4阻害薬の心血管アウトカム試験
試験名
TECOS
EXAMINE
SAVOR-TIMI 53
CAROLINA
対象
2型糖尿病患者
急性冠症候群を合併 2型糖尿病患者
した2型糖尿病患者
2型糖尿病患者
薬剤名
シタグリプチン
アログリプチン
サクサグリプチン
リナグリプチン
対照薬
プラセボ
プラセボ
プラセボ
グリメピリド
登録例数
14,000例
5,400例
16,500例
6,000例
主要
エンドポイント
心血管死，非致死 心血管死，非致死的 心血管死，非致死
的心筋梗塞，非致 心筋梗塞，非致死的 的心筋梗塞，非致
死的脳卒中，不安 脳卒中の複合
死的虚血性脳卒中
狭心症による複合
の複合
心血管死，非致死
的心筋梗塞，非致
死的脳卒中，不安
狭心症による複合
観察期間
5年間
4.75年間
4年間
8.33年間
試験開始
2008年
2009年
2010年
2010年
試験終了予定
2014年12月
2013年12月
2013年7月
2018年9月
綿田裕孝（順天堂大学大学院代謝内分泌内科学）Pharma Medica ;30,8,157-164.2012.
clinicaltrials.gov（http://clinicaltrials.gov/）をもとに一部改変
SAVOR-TIMI 53
N Engl J Med 2013. DOI:
10.1056/NEJMoa1307684
the University of Connecticut School of Medicine, Farmington (W.B.W.); Brigham and
Women’s Hospital and Harvard Medical School (C.P.C.) and Harvard School of Public
Health (C.R.M.) — all in Boston; University of Sheffield, Sheffield, United Kingdom
(S.R.H.); Cleveland Clinic Foundation, Cleveland (S.E.N.); International Diabetes
Center, Park Nicollet Clinic, Minneapolis (R.M.B.); University of Chicago Medicine,
Chicago (G.L.B.); Takeda Development Center Americas, Deerfield, IL (A.T.P., P.R.F,
S.K., C.W.); University of Tennessee College of Medicine, Memphis Veterans Affairs
Medical Center, Memphis (W.C.C.); and INSERM Unite 9501, Universite de Lorraine
and Centre Hospitalier Universitaire, Nancy, France (F.Z.).
N Engl J Med 2013. DOI: 10.1056/NEJMoa1305889
Background To assess potentially elevated
cardiovascular risk related to new
antihyperglycemic drugs in patients with type 2
diabetes, regulatory agencies require a
comprehensive evaluation of the
cardiovascular safety profile of new
antidiabetic therapies. We assessed
cardiovascular outcomes with alogliptin, a new
inhibitor of dipeptidyl peptidase 4 (DPP-4), as
compared with placebo in patients with type 2
diabetes who had had a recent acute coronary
syndrome.
Methods We randomly assigned patients with
type 2 diabetes and either an acute myocardial
infarction or unstable angina requiring
hospitalization within the previous 15 to 90
days to receive alogliptin or placebo in addition
to existing antihyperglycemic and
cardiovascular drug therapy. The study design
was a double-blind, noninferiority trial with a
prespecified noninferiority margin of 1.3 for the
hazard ratio for the primary end point of a
composite of death from cardiovascular
causes, nonfatal myocardial infarction, or
nonfatal stroke.
* Plus–minus values are means
±SD. There were no significant
differences between the two
groups for any baseline
characteristic. ACS denotes acute
coronary syndrome.
† The body-mass index is the
weight in kilograms divided by the
square of the height in meters.
‡ Race or ethnic group was selfreported.
§ Values include the index event
of the acute coronary syndrome.
¶ The estimated glomerular
filtration rate was calculated with
the use of the Modification of Diet
in Renal Disease formula.
* Diuretics included loop diuretics and
thiazide diuretics. Renin–angiotensin
system–blocking agents included
angiotensin-converting–enzyme
inhibitors and angiotensin II–receptor
blockers.
This analysis resulted in a hazard ratio of 0.96 and an
upper boundary of the one-sided repeated confidence
interval of 1.17, findings that indicated noninferiority but
not superiority of alogliptin to placebo, and the
conditional power for superiority at 650 events was less
than 20%; therefore, the data and safety monitoring
committee recommended to the steering committee
that the study be stopped. On March 9, 2013, the
steering committee accepted the recommendation, and
the sponsor agreed to stop enrollment in the study and
proceed with a timely and orderly study closeout. The
final date for evaluation of vital status was June 18,
2013.
Results A total of 5380 patients underwent
randomization and were followed for up to 40
months (median, 18 months). A primary end-point
event occurred in 305 patients assigned to
alogliptin (11.3%) and in 316 patients assigned to
placebo (11.8%) (hazard ratio, 0.96; upper
boundary of the one-sided repeated confidence
interval, 1.16; P<0.001 for noninferiority).
Glycated hemoglobin levels were significantly
lower with alogliptin than with placebo (mean
difference, −0.36 percentage points; P<0.001).
Incidences of hypoglycemia, cancer, pancreatitis,
and initiation of dialysis were similar with
alogliptin and placebo.
Conclusions Among patients with type 2
diabetes who had had a recent acute
coronary syndrome, the rates of major
adverse cardiovascular events were not
increased with the DPP-4 inhibitor alogliptin
as compared with placebo.
(Funded by Takeda Development Center Americas;
EXAMINE ClinicalTrials.gov number, NCT00968708.)
Message
急性冠症候群を最近発症した2型糖尿病（DM）患
者5380人を対象に、アログリプチン投与による
心血管転帰を非劣性試験でプラセボと比較
（EXAMINE試験）。追跡期間中央値18カ月での主
要複合評価項目（心血管死、非致死性心筋梗塞/
脳卒中）発生率はアログリプチン群11.3％、プ
ラセボ群11.8％だった（非劣性P＜0.001）。
Guang Ning,MD, PhD, Key Laboratory for Endocrine and Metabolic Diseases of
Ministry of Health, Department of Endocrine and Metabolic Diseases, Rui-Jin Hospital,
Shanghai Jiao-Tong University School of Medicine, 197 Rui-Jin 2nd Rd, Shanghai,
200025, China ([email protected]);Wenhua Zhao, PhD ([email protected]);
andWeiqingWang, MD, PhD (wqingw @hotmail.com).
JAMA. 2013 Sep 4;310(9):948-59. doi: 10.1001/jama.2013.168118.
IMPORTANCE: Noncommunicable
chronic diseases have become the
leading causes of mortality and disease
burden worldwide.
OBJECTIVE: To investigate the
prevalence of diabetes and glycemic
control in the Chinese adult population.
DESIGN, SETTING, AND PARTICIPANTS Using a
complex, multistage, probability sampling design, we
conducted a cross-sectional survey in a nationally
representative sample of 98 658 Chinese adults in 2010.
MAIN OUTCOMES AND MEASURES Plasma glucose
and hemoglobin A1c levels were measured after at least
a 10-hour overnight fast among all study participants,
and a 2-hour oral glucose tolerance test was conducted
among participants without a self-reported history of
diagnosed diabetes. Diabetes and prediabetes were
defined according to the 2010 American Diabetes
Association criteria; whereas, a hemoglobin A1c level of
<7.0% was considered adequate glycemic control.
Abbreviation: MET,metabolic
equivalent. a There were
85missing values for body mass
index (BMI), which is calculated
as weight in kilograms divided
by height in meters squared,
and 75 missing values for waist
circumference.
SI conversion factors: To convert
plasma glucose to mmol/L,
multiply by 0.0555; total, lowdensity lipoprotein, and highdensity lipoprotein cholesterol to
mmol/L multiply by 0.0259; and
triglycerides to mmol/L, multiply
by 0.0113.
a There were 85 missing values
for body mass index (BMI),
which is calculated as weight in
kilograms divided by height in
meters squared, and 75 missing
values for waist circumference.
Abbreviations: BMI, body mass
index (BMI) is calculated as
weight in kilograms divided by
height in meters squared;
HbA1c, hemoglobin A1c. SI
conversion factor: To convert
plasma glucose to mmol/L,
multiply by 0.0555. a Data are
weighted percentages.
Abbreviation: HbA1c,
hemoglobin A1c. SI conversion
factor: To convert plasma
glucose to mmol/L, multiply by
0.0555. a Data are weighted
percentages. b Body mass index
(BMI) is calculated as weight in
kilograms divided by height in
meters squared.
Abbreviation: BMI, body mass
index, which is calculated as
weight in kilograms divided by
height in meters squared.
a Awareness was defined as the
proportion of individuals who
reported a history of physiciandiagnosed diabetes among all
patients with diabetes. Treatment
was defined as the proportion of
individuals taking diabetes
medications among all patients
with diabetes. Control was defined
as the proportion of individuals
with a hemoglobin A1c level of
less than 7.0% among patients
with diabetes who were treated
with diabetes medications.
bData are weighted percentages.
Abbreviation: OR, odds ratio. SI
conversion factors: To convert
total, low-density lipoprotein, and
high-density lipoprotein
cholesterol to mmol/L, multiply by
0.0259; triglycerides to mmol/L,
multiply by 0.0113. a There were
1432missing values for status of
glucose regulation, 4 missing
values for current smoking, 85
missing values for body mass
index and 75 missing values for
waist circumference. b Numbers
for continuous variables are
values of 1 standard deviation. c
Overweight was defined as a body
mass index (BMI), which is
calculated as weight in kilograms
divided by height in meters
squared, of 25.0-29.9 and obesity
was defined as a BMI of 30.0 or
higher. Central obesity was
defined as waist circumference 90
cm or more in men and 80 cm or
more in women.
RESULTS The overall prevalence of diabetes was estimated to be
11.6%(95%CI, 11.3%-11.8%) in the Chinese adult population. The
prevalence among men was 12.1% (95%CI, 11.7%-12.5%) and
among women was 11.0% (95%CI, 10.7%-11.4%). The
prevalence of previously diagnosed diabetes was estimated to be
3.5%(95%CI, 3.4%-3.6%) in the Chinese population:
3.6%(95%CI, 3.4%-3.8%) in men and 3.4%(95%CI, 3.2%-3.5%) in
women. The prevalence of undiagnosed diabetes was 8.1%
(95%CI, 7.9%-8.3%) in the Chinese population: 8.5%(95%CI,
8.2%-8.8%) in men and 7.7%(95%CI, 7.4%-8.0%) in women. In
addition, the prevalence of prediabetes was estimated to be
50.1%(95%CI, 49.7%-50.6%) in Chinese adults: 52.1% (95%CI,
51.5%-52.7%) in men and 48.1%(95%CI, 47.6%-48.7%) in
women. The prevalence of diabetes was higher in older age
groups, in urban residents, and in persons living in economically
developed regions. Among patients with diabetes, only 25.8%
(95%CI, 24.9%-26.8%) received treatment for diabetes, and only
39.7%(95%CI, 37.6%-41.8%) of those treated had adequate
CONCLUSIONS AND RELEVANCE The
estimated prevalence of diabetes among a
representative sample of Chinese adults
was 11.6%and the prevalence of
prediabetes was 50.1%. Projections based
on sample weighting suggest this may
represent up to 113.9 million Chinese adults
with diabetes and 493.4 million with
prediabetes. These findings indicate the
importance of diabetes as a public health
problem in China.
Message
中国人の成人全国代表標本9万8658人を対象
に、糖尿病の推定有病率を横断研究で調
査。有病率は糖尿病11.6％、前糖尿病
50.1％と推定された。高齢者、都市居住
者、および経済発展地域の居住者ほど糖尿
病有病率が高かった。治療率は25.8％に過
ぎず、このうち十分な血糖コントロールが
得られていたのは39.7％にみだった。