20140423imeglimin - 埼玉医科大学総合医療センター 内分泌

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Journal Club
Fouqueray P1, Pirags V, Inzucchi SE, Bailey CJ,
Schernthaner G, Diamant M, Lebovitz HE.
The efficacy and safety of imeglimin as add-on therapy in
patients with type 2 diabetes inadequately controlled with
metformin monotherapy.
Diabetes Care. 2013 Mar;36(3):565-8. doi: 10.2337/dc120453. Epub 2012 Nov 16.
2014年4月24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
Imeglimin ((6R)-(+)-4-dimethylamino- 2-imino-6methyl-1,2,5,6tetrahydro- 1,3,5, triazine hydrochloride) is the first in a new
tetrahydrotriazine-containing class of oral antidiabetic
agents, the glimins.
It is an oxidative phosphorylation blocker
that acts to inhibit hepatic gluconeogenesis,
increase muscle glucose uptake, and
restore normal insulin secretion.
1Poxel
SA, Lyon, France 2Paul Stradins Clinical University Hospital, Riga, Latvia
3VU University Medical Center, Amsterdam, the Netherlands 4Rudolfstiftung
Hospital, Vienna, Austria 5State University of New York, Health Sciences Center,
Brooklyn, NY 6Yale School of Medicine, New Haven, CT 7Aston University,
Birmingham, U.K.
OBJECTIVE This 12-week study assessed
the efficacy and tolerability of imeglimin as
add-on therapy to the dipeptidyl peptidase-4
inhibitor sitagliptin in patients with type 2
diabetes that was inadequately controlled
with sitagliptin monotherapy.
RESEARCH DESIGN AND METHODS In a
multicenter, randomized, double-blind, placebocontrolled, parallel-group study, imeglimin (1,500
mg b.i.d.) or placebo was added to sitagliptin (100
mg q.d.) over 12 weeks in 170 patients with type
2 diabetes (mean age 56.8 years; BMI 32.2
kg/m2) that was inadequately controlled with
sitagliptin alone (A1C ≧7.5%) during a 12-week
run-in period. The primary efficacy end point was
the change in A1C from baseline versus placebo;
secondary end points included corresponding
changes in fasting plasma glucose (FPG) levels,
stratification by baseline A1C, and percentage of
A1C responders.
Supplementary Figure 1.
Summary of subject
disposition
Abbreviations: ITT = Intention-to-treat; PP
= Per-protocol
Figure 2—A: Effect of sitagliptin-imeglimin vs. sitagliptin-placebo: A1C reductions over the 12- week double-blind
treatment period. B: Effect of sitagliptin-imeglimin vs. sitagliptin-placebo: change in A1C depending on baseline A1C value.
TEAEs: treatment-emergent adverse events
RESULTS Imeglimin reduced A1C levels (leastsquares mean difference) from baseline (8.5%) by
0.60% compared with an increase of 0.12% with
placebo (betweengroup difference 0.72%, P < 0.001).
The corresponding changes in FPG were 20.93
mmol/L with imeglimin vs. 20.11 mmol/L with placebo
(P = 0.014). With imeglimin, the A1C level decreased
by ‡0.5% in 54.3% of subjects vs. 21.6% with
placebo (P < 0.001), and 19.8%of subjects receiving
imeglimin achieved a decrease in A1C level of £7%
compared with subjects receiving placebo (1.1%) (P
= 0.004). Imeglimin was generally well-tolerated, with
a safety profile comparable to placebo and no
related treatment-emergent adverse events.
CONCLUSIONS Imeglimin demonstrated
incremental efficacy benefits as add-on
therapy to sitagliptin, with comparable
tolerability to placebo, highlighting the
potential for imeglimin to complement other
oral antihyperglycemic therapies.
Message
Imegliminという物質も糖尿病治療に使えそうと
いう論文。
1Poxel
SA, Lyon, France
2Department of Internal Medicine, Paul Stradins Clinical University Hospital, Riga, Latvia
3Section of Endocrinology, Yale School of Medicine, New Haven, Connecticut
4School of Life and Health Sciences, Aston University, Birmingham, United Kingdom
5Department of Internal Medicine, Rudolfstiftung Hospital, Vienna, Austria
6Diabetes Center/Department of Internal Medicine, VU University Medical Center,
Amsterdam, the Netherlands
7Department of Medicine, State University of New York, Health Sciences Center, Brooklyn,
New York
Diabetes Care 36:565–568, 201
OBJECTIVE A 12-week study assessed the
efficacy and safety of a new oral antidiabetic
agent, imeglimin, as add-on therapy in type
2 diabetes patients inadequately controlled
with metformin alone.
RESEARCH DESIGN AND METHODS A
total of 156 patients were randomized 1:1 to
receive imeglimin (1,500 mg twice a day) or
placebo added to a stable dose of
metformin (1,500–2,000 mg/day). Change
in A1C from baseline was the primary
efficacy outcome; secondary outcomes
included fasting plasma glucose (FPG) and
proinsulin/insulin ratio.
RESULTS After 12 weeks, the placebosubtracted decrease in A1C with metforminimeglimin was −0.44% (P < 0.001).
Metformin-imeglimin also significantly
improved FPG and the proinsulin/insulin
ratio from baseline (−0.91 mg/dL and −7.5,
respectively) compared with metforminplacebo (0.36 mg/dL and 11.81). Metforminimeglimin therapy was generally welltolerated with a comparable safety profile to
metformin-placebo.
CONCLUSIONS Addition of imeglimin to
metformin improved glycemic control and
offers potential as a new treatment for type
2 diabetes.
テトラヒドロトリアジンを含む全く新しいクラスの経口糖尿病
治療薬(glimins) として注目されているものの1つに
imegliminがある。同薬に関する2件の概念実証(proofof-concept)試験は終了しており,現在,第Ⅱ相臨床試験
でメトホルミンへのimegliminの上乗せ効果が検証されてい
る。同薬を開発しているPoxel社のPascale Fouqueray氏
は「メトホルミン単剤治療でのコントロールが不十分な2型糖
尿病患者にimegliminを上乗せ投与すれば,より良好な血
糖管理が見込め,忍容性にも問題ないことが12週間の第Ⅱ
相ランダム化比較試験(RCT)により示された」とDiabetes
Care 2012年11月16日オンライン版で報告した。同薬の作
用機序としては,2型糖尿病の3大病態を改善する可能性が
指摘されている。

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