Journal Club 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 2012 年 2 月 2 日 8:30-8:55 ８階 医局 Sjöström L, Peltonen M, Jacobson P, Sjöström CD, Karason K, Wedel H, Ahlin S, Anveden Å, Bengtsson C, Bergmark G, Bouchard C, Carlsson B, Dahlgren S, Karlsson J, Lindroos AK, Lönroth H, Narbro K, Näslund I, Olbers T, Svensson PA, Carlsson LM. Bariatric surgery and long-term cardiovascular events. JAMA Jan 4;307(1): Vilsbøll T, Christensen M, Junker AE, Knop FK, Gluud LL. Effects of glucagon-like peptide-1 receptor agonists on weight loss: systematic review and meta-analyses of randomised controlled trials. BMJ Jan 10;344:d7771. doi: /bmj.d7771.

The LABS writing group assumes responsibility for the content of this article. Members of the LABS writing group are listed in the Appendix. Address reprint requests to Dr. David R. Flum at the Surgical Outcomes Research Center, Department of Surgery, University of Washington N Engl J Med 2009;361: 年８月６日

減量手術 245 件 （内訳） 腹腔鏡下胃バイパス手 術 143 件 腹腔鏡下袖状胃切除術 58 件 ラップバンド手術 17 件 腹腔鏡下 BPD/DS 27 件 その他 胃内バルーン挿入術 7件7件 Laparoscopic Roux en Y Gastric Bypass: LRYGB Laparoscopic Gastric Banding BIB Before After Dr. Kasama

胃バイパス術バンディング術減量手術全体 超過体重減少率 1 ） 61.60%47.50%61.20% 平均体重減少ｋｇ 1 ） 43.5kg28.6kg39.7kg 術死率 1 ） 0.50%0.10% 術後合併症率 2 ） 7.90%7.20% 再手術率 2 ） 1.10%5.30% 満足しない減量の率 2 ） 1.00%13.00% 糖尿病治癒率／改善率 1 ） 83.7% / 93.2%47.9% / 80.8%76.8% / 86.0% 高血圧治癒率／改善率 1 ） 67.5% / 87.2%43.2% / 70.8%61.7% / 78.5% 高脂血症改善率 1 ） 96.90%58.90%79.30% 睡眠時無呼吸改善率 1 ） 94.80%68%83.60% 1) Bariatric surgery: a systematic review and meta-analysis. Buchwald H, Avidor Y, Braunwald E et al: JAMA : ) Brazil Sao Paulo Gastro Obeso Center での同一スタッフによる腹腔鏡下胃バイパス 術 :2012 人、腹腔鏡下バンディング術 1174 人の検討（ 2005 年 IFSO 発表）

JAMA. 2010;304(4): Department of Surgery, and Center for Healthcare Outcomes and Policy (CHOP) (Drs N. Birkmeyer, Dimick, Finks, and J. Birkmeyer), and Department of Family Medicine (Dr Share), University of Michigan, Ann Arbor; Department of Surgery, St John Hospital and Medical Center, Detroit, Michigan (Dr Hawasli); Department of Surgery, Marquette General Hospital, Marquette, Michigan (Dr English); and Department of Surgery, Henry Ford Hospital, Detroit, Michigan (Drs Genaw and Carlin). Corresponding Author: Nancy J. O. Birkmeyer, PhD, Michigan Surgical Collaborative for Outcomes Research and Evaluation (M- SCORE), Department of Surgery, University of Michigan, 211 N Fourth Ave, Ste 2A and 2B, Ann Arbor, MI a reduction in mortality of 23% from 40%! some obese young adults may lose up to 20 years of life expectancy if they do not reduce their weight 2010 年 8 月 19 日

A meta-analysis from University of California, Los Angeles reports the following weight loss at 36 months Biliopancreatic diversion - 53 kg Roux-en-Y gastric bypass (RYGB) - 41 kg Open - 42 kg Laparoscopic - 38 kg Adjustable gastric banding - 35 kg Vertical banded gastroplasty - 32 kg Sleeve gastrectomy ? Biliopancreatic diversion Roux-en-Y gastric bypass Sleeve gastrectomy with duodenal switch Adjustable gastric banding Vertical banded gastroplasty

JAMA. 2012;307(1):56-65 Institutes of Medicine (Drs L. Sjöström, Jacobson, C. Sjöström, Karason, Ahlin, Anveden, B. Carlsson, Svensson, and L. Carlsson and Ms Bergmark), Surgery (Drs Lo¨ nroth and Olbers), Primary Health Care (Dr Bengtsson), and Health and Care Sciences (Dr Karlsson), The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Chronic Disease Epidemiology and Prevention Unit, National Institute for Health and Welfare, Helsinki, Finland (Dr Peltonen); Nordic School of Public Health, Gothenburg, Sweden (DrWedel); Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge (Dr Bouchard); Department of Surgery, Umeå University Hospital, Umeå, Sweden (Dr Dahlgren); Nutrition Department, National Food Administration, Uppsala, Sweden (Dr Lindroos); Department of Health Care, Region Västra Götaland, Gothenburg, Sweden (Dr Narbro); and Department of Surgery, University Hospital,Örebro, Sweden (Dr Na¨ slund).

Context Obesity is a risk factor for cardiovascular events. Weight loss might protect against cardiovascular events, but solid evidence is lacking. Objective To study the association between bariatric surgery, weight loss, and cardiovascular events.

Design, Setting, and Participants The Swedish Obese Subjects (SOS) study is an ongoing, nonrandomized, prospective, controlled study conducted at 25 public surgical departments and 480 primary health care centers in Sweden of 2010 obese participants who underwent bariatric surgery and 2037 contemporaneously matched obese controls who received usual care. Patients were recruited between September 1, 1987, and January 31, Date of analysis was December 31, 2009, with median follow-up of 14.7 years (range, years). Inclusion criteria were age 37 to 60 years and a body mass index of at least 34 in men and at least 38 in women. Exclusion criteria were identical in surgery and control patients. Surgery patients underwent gastric bypass (13.2%), banding (18.7%), or vertical banded gastroplasty (68.1%), and controls received usual care in the Swedish primary health care system. Physical and biochemical examinations and database cross-checks were undertaken at preplanned intervals. Main Outcome Measures The primary end point of the SOS study (total mortality) was published in Myocardial infarction and stroke were predefined secondary end points, considered separately and combined.

Results Bariatric surgery was associated with a reduced number of cardiovascular deaths (28 events among 2010 patients in the surgery group vs 49 events among 2037 patients in the control group; adjusted hazard ratio [HR], 0.47; 95% CI, 0.29 － 0.76; P=.002). The number of total first time (fatal or nonfatal) cardiovascular events (myocardial infarction or stroke, whichever came first) was lower in the surgery group (199 events among 2010 patients) than in the control group (234 events among 2037 patients; adjusted HR, 0.67; 95% CI, ; P<.001).

Conclusion Compared with usual care, bariatric surgery was associated with reduced number of cardiovascular deaths and lower incidence of cardiovascular events in obese adults.

Message スウェーデンで肥満患者を対象に、肥満 手術と心血管イベントの関連を非無作為 化前向き対照試験（ SOS 試験）で検証。 心血管死は手術群 2010 人中 28 人、通常 治療群 2037 人中 49 人で、肥満手術と心 血管死の減少に関連が見られた（調整後 ハザード比 0.47 ）。初発心血管イベント は手術群 199 人、通常治療群 234 人で発 生が見られた。

Published online October 23, 2009 DOI: /S (09) Novo Nordisk now plans to re-initiate the global phase 3 programme in the first half of 2011 in clinical trials comprising approximately 5,000 patients (June 22, 2010)

Objective To determine whether treatment with agonists of glucagon-like peptide-1 receptor (GLP-1R) result in weight loss in overweight or obese patients with or without type 2 diabetes mellitus.

Design Systematic review with meta-analyses. Data sources Electronic searches (Cochrane Library, Medline, Embase, and Web of Science) and manual searches (up to May 2011). Review methods Randomised controlled trials of adult participants with a body mass index of 25 or higher; with or without type 2 diabetes mellitus; and who received exenatide twice daily, exenatide once weekly, or liraglutide once daily at clinically relevant doses for at least 20 weeks. Control interventions assessed were placebo, oral antidiabetic drugs, or insulin. Data extraction Three authors independently extracted data. We used random effects models for the primary meta- analyses. We also did subgroup, sensitivity, regression, and sequential analyses to evaluate sources of intertrial heterogeneity, bias, and the robustness of results after adjusting for multiple testing and random errors.

Fig 2 Meta-analysis of change in body weight (kg) in included trials after at least 20 weeks of treatment, using random effects model

Fig 3 Meta-analysis of change in systolic blood pressure (mm Hg) in included trials after at least 20 weeks of treatment, using random effects model

Fig 4 Meta-analysis of change in diastolic blood pressure (mm Hg) in included trials after at least 20 weeks of treatment, using random effects model

Fig 5 Meta-analysis of change in concentration of total cholesterol (mmol/L) in included trials after at least 20 weeks of treatment, using random effects model

Fig 6 Meta-analysis of change in concentration of alanine aminotransferase (U/L) in included trials after at least 20 weeks of treatment, using fixed effects model

Fig 7 Meta-analysis of reduction in HbA1c percentage in included trials after at least 20 weeks of treatment, using random effects model

Results 25 trials were included in the analysis. GLP-1R agonist groups achieved a greater weight loss than control groups (weighted mean difference −2.9 kg, 95% confidence interval –3.6 to –2.2; 21 trials, 6411 participants). We found evidence of intertrial heterogeneity, but no evidence of bias or small study effects in regression analyses. The results were confirmed in sequential analyses. We recorded weight loss in the GLP-1R agonist groups for patients without diabetes (–3.2 kg, –4.3 to –2.1; three trials) as well as patients with diabetes (–2.8 kg, –3.4 to –2.3; 18 trials). In the overall analysis, GLP-1R agonists had beneficial effects on systolic and diastolic blood pressure, plasma concentrations of cholesterol, and glycaemic control, but did not have a significant effect on plasma concentrations of liver enzymes. GLP-1R agonists were associated with nausea, diarrhoea, and vomiting, but not with hypoglycaemia.

Conclusions The present review provides evidence that treatment with GLP-1R agonists leads to weight loss in overweight or obese patients with or without type 2 diabetes mellitus.

Message 医学文献データベース Medline などから選択し た 25 件の試験を対象に、過体重または肥満患者 へのグルカゴン様ペプチド -1 受容体（ GLP- 1R ）作動薬の減量効果をメタ解析とシステマ ティックレビューで評価。 2 型糖尿病を有する 患者（対照群との平均減量差 2.8kg ）、非糖尿 病患者（同 3.2kg ）のいずれにも減量効果が見 られた。 血糖低下、コレステロール低下、血圧低下も！ （肝臓酵素は解析法によっては有意に低下）