Journal Club

1. Journal Club DAVID M. NATHAN, MD, JOHN B. BUSE, MD, PHD, MAYER B. DAVIDSON, MD, ELE FERRANNINI, MD, RURY R. HOLMAN, FRCP, ROBERT SHERWIN, MD, BERNARD ZINMAN, MD Medical Management of Hyperglycemia inType 2 Diabetes: A Consensus Algorithm for the Initiation and Adjustment of Therapy A consensus statement of the American Diabetes Association and the European Association for the Study of Diabetes Diabetes Care 32:1–11,2009 亀田メディカルセンター　糖尿病内分泌内科 Diabetes and Endocrine Department, Kameda Medical Center 松田　昌文 Matsuda, Masafumi 2008年12月4日　8:20-8:50 B棟８階　カンファレンス室

2. インスリン治療 経口血糖降下薬 ＋ 基礎インスリン 混合型 インスリン 基礎インスリン ＋追加インスリン （強化インスリン療法） 2型糖尿病の治療 食事・運動療法 経口血糖 降下薬 （単剤） 経口血糖 降下薬 （併用） インスリン 導入

3. 1Diabetes Center, Massachusetts General Hospital, Boston, Massachusetts; the 2University of North Carolina School of Medicine, Chapel Hill, North Carolina; the 3Clinical Center for Research Excellence, Charles R. Drew University, Los Angeles, California; the 4Department of Internal Medicine, University of Pisa, Pisa, Italy; the 5Diabetes Trials Unit, Oxford Centre for Diabetes, Endocrinology and Metabolism, Oxford University, Oxford, U.K.; the 6Department of Internal Medicine and Yale Center for Clinical Investigation, Yale University School of Medicine, New Haven, Connecticut; and the 7Samuel Lunenfeld Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada.

4. 1963-1972

7. 2006年　ADA/EASDコンセンサス2型糖尿病治療のアルゴリズム2006年　ADA/EASDコンセンサス2型糖尿病治療のアルゴリズム HbA1Cを3ヵ月毎にチェック 7％以上：次の段階へ 7％未満：そのまま治療継続 　　　　 少なくとも6ヵ月ごとに HbA1Cをチェック 診断 生活習慣改善＋メトホルミン 低血糖なし 最も有効 最も安価 ＋基礎インスリン ＋SU薬 ＋チアゾリジン薬 インスリン頻回注射 ＋チアゾリジン薬 ＋基礎インスリン ＋SU薬 基礎インスリン、または インスリン頻回注射 強化インスリン療法＋メトホルミン±チアゾリジン薬 Nathan DM, et al. Diabetes Care 2006;29:1963-1971

9. Figure 2—Algorithm for the metabolic management of type 2 diabetes; Reinforce lifestyle interventions at every visit and check A1C every 3 months until A1C is <7% and then at least every 6 months. The interventions should be changed if A1C is >7%. Sulfonylureas other than glybenclamide (glyburide) or chlorpropamide. Insufficient clinical use to be confident regarding safety. See text box, entitled TITRATION OF METFORMIN. See Fig. 1 for initiation and adjustment of insulin. CHF, congestive heart failure.

10. 2型糖尿病管理のアルゴリズム ＊Premix製剤はインスリン導入のレジメンには推奨しない。 1:確証の得られた中心的な治療法 診断： ライフスタイル + メトホルミン ライフスタイル+メトホルミン + 基礎インスリン ライフスタイル+メトホルミン + 強化インスリン療法 ライフスタイル+メトホルミン + SU薬 ＊SU薬はグリベンクラミド、 クロルプロパミド以外を使用 STEP1 STEP2 STEP3 2:確証の不十分な治療法 ライフスタイル+メトホルミン + ピオグリタゾン + SU薬 ライフスタイル+メトホルミン + ピオグリタゾン 低血糖無し 浮腫/CHF・骨折 ライフスタイル+メトホルミン + 基礎インスリン ライフスタイル+メトホルミン + GLP-1 アナログ 低血糖無し・体重減少 嘔気/嘔吐 DIABETES CARE, VOLUME 31, NUMBER 12, DECEMBER 2008 Figure 2

12. TITRATION OF METFORMIN 1. Begin with low-dose metformin (500 mg) taken once or twice per day with meals (breakfast and/or dinner) or 850 mg once per day. 2. After 5–7 days, if gastrointestinal side effects have not occurred, advance dose to 850, or two 500 mg tablets, twice per day (medication to be taken before breakfast and/or dinner). 3. If gastrointestinal side effects appear as doses advanced, decrease to previous lower dose and try to advance the dose at a later time. 4. The maximum effective dose can be up to 1,000 mg twice per day but is often 850 mg twice per day. Modestly greater effectiveness has been observed with doses up to about 2,500 mg/day. Gastrointestinal side effects may limit the dose that can be used. 5. Based on cost considerations, generic metformin is the first choice of therapy. A longer-acting formulation is available in some countries and can be given once per day.

13. Figure 1—Initiation and adjustment of insulin regimens. Insulin regimens should be designed taking lifestyle and meal schedule into account. The algorithm can only provide basic guidelines for initiation and adjustment of insulin. See reference 90 for more detailed instructions. Premixed insulins not recommended during adjustment of doses; however, they can be used conveniently, usually before breakfast and/or dinner, if proportion of rapid- and intermediate-acting insulins is similar to the fixed proportions available. bg, blood glucose.

14. Special considerations/patients In the setting of severely uncontrolled diabetes with catabolism, defined as • fasting plasma glucose levels >13.9 mmol/l (250 mg/dl) • random glucose levels consistently >16.7 mmol/l (300 mg/dl) • HbA1c >10% • the presence of ketonuria • as symptomatic diabetes with polyuria, polydipsia and weight loss Insulin therapy in combination with lifestyle intervention is the treatment of choice. Some patients with these characteristics will have unrecognised type 1 diabetes; others will have type 2 diabetes but with severe insulin deficiency. Insulin can be titrated rapidly and is associated with the greatest likelihood of returning glucose levels rapidly to target levels. After symptoms are relieved, oral agents can often be added and it may be possible to withdraw insulin, if preferred.

15. Summary The guidelines and treatment algorithm presented here emphasise the following − Achievement and maintenance of normal glycaemic goals − Initial therapy with lifestyle intervention and metformin − Rapid addition of medications, and transition to new regimens, when target glycaemic goals are not achieved or sustained − Early addition of insulin therapy in patients who do not meet target goals Diabetologia (2006) 49:1711–1721 1719

16. Summary The guidelines and treatment algorithm presented here emphasize the following: ● Achievement and maintenance of near normoglycaemia (A1C< 7.0%) ● Initial therapy with lifestyle intervention and metformin ●Rapid addition of medications, and transition to new regimens, when target glycemic goals are not achieved or sustained ●Early addition of insulin therapy in patients who do not meet target goals