Long-Term Safety, Tolerability, and Weight Loss Associated With Metformin in the Diabetes Prevention Program Outcomes Study

被引：343

作者：

Bray, George A. ^{[1
]}

Edelstein, Sharon L. ^{[2
]}

Crandall, Jill P. ^{[3
]}

Aroda, Vanita R. ^{[4
]}

Franks, Paul W. ^{[5
,6
]}

Fujimoto, Wilfred ^{[7
]}

Horton, Edward ^{[8
]}

Jeffries, Susan ^{[9
]}

Montez, Maria ^{[10
]}

Mudaliar, Sunder ^{[11
]}

Pi-Sunyer, F. Xavier ^{[12
]}

White, Neil H. ^{[13
]}

Knowler, William C. ^{[14
]}

机构：

[1] Pennington Biomed Res Ctr, Baton Rouge, LA USA

[2] George Washington Univ, Ctr Biostat, Rockville, MD USA

[3] Albert Einstein Coll Med, Bronx, NY 10467 USA

[4] Medstar Hlth Res Inst, Hyattsville, MD USA

[5] Lund Univ, Ctr Diabet, Skane Univ Hosp, Malmo, Sweden

[6] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA

[7] Univ Washington, Seattle, WA 98195 USA

[8] Joslin Diabet Ctr, Boston, MA 02215 USA

[9] Univ Pittsburgh, Pittsburgh, PA USA

[10] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA

[11] Univ Calif San Diego, San Diego, CA 92103 USA

[12] Columbia Univ, St Lukes Roosevelt Hosp Ctr, New York, NY USA

[13] Washington Univ, Sch Med, St Louis, MO USA

[14] NIDDK, Phoenix, AZ USA

来源：

DIABETES CARE | 2012年 / 35卷 / 04期

基金：

美国国家卫生研究院; 瑞典研究理事会;

关键词：

ACTIVATED PROTEIN-KINASE; LIFE-STYLE INTERVENTION; TYPE-2; THERAPY; OBESITY; MUSCLE; DIET;

D O I：

10.2337/dc11-1299

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

OBJECTIVE-Metformin produced weight loss and delayed or prevented diabetes in the Diabetes Prevention Program (DPP). We examined its long-term safety and tolerability along with weight loss, and change in waist circumference during the DPP and its long-term follow-up. RESEARCH DESIGN AND METHODS-The randomized double-blind clinical trial of metformin or placebo followed by a 7-8-year open-label extension and analysis of adverse events, tolerability, and the effect of adherence on change in weight and waist circumference. RESULTS-No significant safety issues were identified. Gastrointestinal symptoms were more common in metformin than placebo participants and declined over time. During the DPP, average hemoglobin and hematocrit levels were slightly lower in the metformin group than in the placebo group. Decreases in hemoglobin and hematocrit in the metformin group occurred during the first year following randomization, with no further changes observed over time. During the DPP, metformin participants had reduced body weight and waist circumference compared with placebo (weight by 2.06 +/- 5.65% vs. 0.02 +/- 5.52%, P < 0.001, and waist circumference by 2.13 +/- 7.06 cm vs. 0.79 +/- 6.54 cm, P < 0.001 in metformin vs. placebo, respectively). The magnitude of weight loss during the 2-year double-blind period was directly related to adherence (P < 0.001). Throughout the unblinded follow-up, weight loss remained significantly greater in the metformin group than in the placebo group (2.0 vs. 0.2%, P < 0.001), and this was related to the degree of continuing metformin adherence (P < 0.001). CONCLUSIONS-Metformin used for diabetes prevention is safe and well tolerated. Weight loss is related to adherence to metformin and is durable for at least 10 years of treatment.

引用

页码：731 / 737

页数：7

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