Transcript PowerPoint プレゼンテーション - 埼玉医科大学総合医療センター 内分泌

Journal Club
Phung OJ, Scholle JM, Talwar M, Coleman CI
Effect of Noninsulin Antidiabetic Drugs Added to Metformin Therapy on
Glycemic Control, Weight Gain, and Hypoglycemia
in Type 2 Diabetes
JAMA. 2010;303(14):1410-1418
Ruilope LM, Dukat A, Böhm M, Lacourcière Y, Gong J, Lefkowitz MP.
Blood-pressure reduction with LCZ696, a novel dual-acting inhibitor of the
angiotensin II receptor and neprilysin: a randomised, double-blind, placebocontrolled, active comparator study.
Lancet. 2010 Apr 10;375(9722):1255-66.
2010年４月15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
Matsuda, Masafumi
Diabetes Care 32:193–203, 2009
University of Connecticut School of
Pharmacy, Storrs, and Drug Information
Center, Hartford Hospital, Hartford,
Connecticut.
JAMA. 2010;303(14):1410-1418
Aim
Context Metformin is the recommended initial
drug therapy for patients with type 2 diabetes
mellitus (DM). However, the optimal secondline drug when metformin monotherapy fails is
unclear.
Objective To determine the comparative
efficacy, risk of weight gain, and hypoyglycemia
associated with noninsulin antidiabetic drugs in
patients with type 2 DM not controlled by
metformin alone.
Methods
Data Sources A literature search via MEDLINE (beginning in January 1950)
and Cochrane CENTRAL through January 2010 and a manual search of
references for additional relevant studies.
Study Selection Randomized controlled trials (RCTs) with at least 3 months’
duration, evaluating noninsulin antidiabetic drugs added to metformin in
patients experiencing an inadequate response to maximized and stable (_4
weeks at _1500 mg or maximally tolerated dose) metformin therapy.
Data Extraction Inclusion/exclusion criteria; duration of patient follow-up; drug,
dose, and schedule used; use of concurrent lifestyle modification; and baseline
characteristics (age, sex, anthropometrics, glycated hemoglobin A1c [HbA1c],
duration of DM, and metformin dose). End points collected included mean
change in HbA1c, proportion of patients achieving HbA1c goal of less than 7%,
change in weight, and incidence of hypoglycemia. Mixed-treatment comparison
meta-analysis was used to calculate the weighted mean difference for changes
from baseline in HbA1c and body weight and relative risk (RR) of HbA1c goal
attainment and hypoglycemia, with associated 95% credible intervals.
Figure.
Flow Diagram of RCTs Evaluating
the Use of Noninsulin Antidiabetic
Drugs Added to Metformin in
Patients With Type 2 Diabetes
RCTs indicate randomized
controlled trials.
aProvided
information about
study design or patient
demographics.
ΔHbA1C
Jadad Score: Oxford quality scoring system (highest quality to lowest)
Was the study described as randomized? yes and good=2, yes but not good=1, no=0
Was the study described as double blind? yes and good=2, yes but not good=1, no=0
Was there a description of withdrawals and dropouts? yes =1, no=0
Results
Data Synthesis Overall, 27 RCTs (n=11 198) were
included. Mean (range) trial duration was 32 (12-52)
weeks. The different classes of drugs were associated
with similar HbA1c reductions (range, 0.64%0.97%) compared with placebo. Although use of
thiazolidinediones, sulfonylureas, and glinides were
associated with weight gain (range, 1.77-2.08 kg),
glucagon-like peptide-1 analogs, α-glucosidase
inhibitors, and dipeptidyl peptidase-4 inhibitors were
associated with weight loss or no weight change.
Sulfonylureas and glinides were associated with
higher rates of hypoglycemia than with placebo (RR
range, 4.57-7.50).
Conclusion
When added to maximal metformin
therapy, all noninsulin antidiabetic
drugs were associated with similar
HbA1c reductions but differed in
their associations with weight gain
and risk of hypoglycemia.
Message
欧米はメトホルミンから開始するが２番目の薬
物は？
どれも同程度の血糖降下作用があるという？？
（SUやGLP-1は低下するはずだが？？？）
SU薬を１番目の薬物とした場合は？
Division of Hypertension, Hospital 12 de Octubre, Madrid, Spain (Prof L M Ruilope MD);
Second Department of Internal Medicine, Comenius University, Bratislava, Slovakia (Prof
A Dukat MD); Department of Internal Medicine III, Cardiology, Angiology, and Intensive
Care, Universitat des Saarlandes, Homburg/Saar, Germany (Prof M Bohm MD);
Hypertension Research Unit, Centre Hospitalier de l’Universite Laval, QC, Canada (Y
Lacourciere MD); and Novartis Pharmaceuticals, East Hanover, NJ, USA (J Gong PhD, M P
Lefk owitz MD)
This trial is registered with ClinicalTrials.gov, number NCT00549770.
Lancet 2010; 375: 1255–66
Background
LCZ696 is a first-in-class inhibitor of the
angiotensin II receptor and neprilysin.
We aimed to establish whether the dual
actions of LCZ696 lead to further
lowering of blood pressure, compared
with the angiotensinreceptor blocker
valsartan.
Method
1328 patients aged 18–75 years with mild-tomoderate hypertension were randomly assigned
(double-blind) to 8 weeks’ treatment in one of eight
groups: 100 mg (n=156 patients), 200 mg (n=169), or
400 mg (n=172) LCZ696; 80 mg (n=163), 160 mg
(n=166), or 320 mg (n=164) valsartan; 200 mg
AHU377 (n=165); or placebo (n=173). The primary
endpoint was the mean difference across the three
single-dose pairwise comparisons of LCZ696
versus valsartan (100 mg vs 80 mg, 200 mg vs 160
mg, and 400 mg vs 320 mg) in mean sitting diastolic
blood pressure during the 8-week treatment period.
Analysis was by intention to treat.
Data are mean (SD) or number of patients (%). *Data supplied for 170 patients on placebo, 164 on 200 mg
AHU377, 154 on 100 mg LCZ696, 168 on 200 mg LCZ696, 172 on 400 mg LCZ696, 162 on 80 mg valsartan, 166
on 160 mg valsartan, and 162 on 320 mg valsartan; data were missing for remaining patients. †Data were
recorded at study entry (week 0) apart from blood pressure measurements, which were recorded at baseline
(week 4) just before patients were given the first dose of study drug.
Systolic BP
Diastolic BP
Systolic BP
Diastolic BP
Results
1215 patients completed the 8-week treatment period.
The average reduction in mean sitting diastolic blood
pressure across the doses of LCZ696 versus the
appropriate comparator dose of valsartan showed
significantly greater reductions with LCZ696 (mean
reduction: –2・17 mm Hg, 95% CI –3・28 to –1・06; p<0・
0001). The reduction in mean sitting diastolic blood
pressure was significantly different for 200 mg LCZ696
versus 160 mg valsartan (–2・97 mm Hg, 95% CI –4・88 to
–1・07, p=0・0023) and for 400 mg LCZ696 versus 320 mg
valsartan (–2・70 mm Hg, –4・61 to –0・80, p=0・0055).
LCZ696 was well tolerated and no cases of angiooedema were reported; only three serious adverse
events occurred during the 8-week treatment period, of
which none was judged to be related to the study drug,
and no patients died.
Conclusion
Compared with valsartan, dualacting LCZ696 provides
complementary and fully additive
reduction of blood pressure, which
suggests that the drug holds
promise for treatment of
hypertension and cardiovascular
disease.
Message
1つの分子に２つの作用点のある降圧薬！
副作用軽減で有用性があるという。
合剤でもよいかもしれないが？？？