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A Peer-Reviewed Publication
January 2011
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EDITORIAL MESSAGE ....................3 EDITORIAL BOARD.........................6 REVIEW Preoperative Risk Reduction .......8 REVIEW Insulin Resistance and the Use of Metformin: Effects on Body Weight ...............................10 NUTRITIONAL CONSIDERATIONS IN THE BARIATRIC PATIENT Bariatric Beriberi: Thiamin Deficiency in the Bariatric Patient........................................14 SYMPOSIUM SYNOPSIS 11th Annual Conference on Obesity .......................................15 INTERVIEW Mid-term Perspective from the Man Wearing the Badge: An Interview with ASBMS President Bruce M. Wolfe, MD....................18 BARIATRIC CENTER SPOTLIGHT The Obesity Treatment Center at Catholic Medical Center.............22 RESEARCH BITES ........................26 NEWS AND TRENDS ....................27 JOURNAL WATCH ........................28 CALENDAR OF EVENTS ................30 MARKETPLACE ...........................30 AD INDEX ....................................31
CATO SERIES
CATO SERIES
INTRODUCTION
Obesity remains a growing and ongoing problem in the United States. While recent reports have shown obesity rates have stabilized, severe classes of obesity are on the rise,1 having important implications in regard to treatment. Weight loss surgery remains a durable treatment for obesity, effectively resulting in remission of many obesity-related conditions.2 In addition, recent reports have demonstrated a mortality benefit in patients who have had bariatric surgery.3 As a result, weight loss surgeries are on the rise. Studies have shown a five-fold increase in the number of bariatric surgeries between 1998 and 2003.4 The number of weight loss surgeries performed in the United States has
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Review
ABSTRACT
Metformin is a widely perscribed drug for the treatment of diabetes and is often used off label for the treatment of prediabetes and insulin resistance. In addition to its primary use, metformin has often been cited as having weight loss benefits. This article reviews the concept of insulin resistance as it pertains to body weight and the effects of meformin on body weight in subgroups of patients with and without diabetes.
known to cause glucose transporter GLUT4 deployment to the plasma membrane, resulting in insulinindependent glucose uptake.
KEY WORDS
metformin, obesity, insulin resistance
Continued from page 1 Insulin resistance affects several organ systems and predisposes patients to several metabolic disorders. Connections between insulin resistance and other aspects of the metabolic syndrome, such as dyslipidemia, hypertension, prothrombotic state, and glucose intolerance, are complex. Insulin resistance may contribute directly or indirectly to these conditions. 3 It is important to note that insulin resistance predates diabetes by years. Assuming the metabolic effects of insulin resistance are in play years before a numeric diagnosis of diabetes, it is easy to see how the physiologic insults can occur prior to any awareness of the metabolic disarray.
3. Lifestyle (not to be forgotten or outdone) was more effective than metformin alone in preventing the development of diabetes
Prevention of Risks in Obesity Study.10 This study enrolled 324 patients with waist-to-hip ratios of >0.95 in men and >0.80 in women as a surrogate for insulin resistance. Subjects were randomized to lowdose metformin 850mg daily or to placebo for one year. Data showed a trend toward benefit in the metformin group. The second trial in Table 2 looked at 150 women with body mass index (BMI)>30mg/m,2 and the third trial looked at men and women with morbid obesity.11,12 These trials were short and small in number but demonstrated a decrease in body weight with metformin. Table 3 lists subjects without diabetes with impaired glucose tolerance (IGT). The DPP trial enrolled a population of over 3,000 subjects with IGT and a mean BMI of 34kg/m2 with benefits as noted.4 No effect was observed in a threeyear Chinese study.13 The final study listed in Table 3 is a Swedish study that showed metformin demonstrated some benefit in weight loss, but this was not statistically significant.14
Review
Med. 2003;41:215225. Grisouard J, Timper K, Radimerski TM, et al. Mechanisms of metformin action on glucose transport and metabolism in human adipocytes. Biochem Pharmacol. 2010;80(11):17361745. Correia S, Carvalho C, Santos MS, et al. Mechanisms of action of metfromin in type 2 diabetes and associated complications: an overview. Mini Rev Med Chem. 2008;8(13):13431354. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). UK Prospective Diabetes Study (UKPDS) Group. Lancet. 1998;352(9131):854865. Kahn SE, Haffner SM, Heise MA, et al. Glycemic durability of rosiglitazone, metformin or glyburide monotherapy. N Engl J Med. 2006;355:24272443. Fontbonne A, Charles MA, JuhanVague I, et al. The effect of metformin on the metabolic abnormalities associated with upper body fat distribution BIGPRO study group. Diabetes Care. 1996;19:920926. Gokcel A, Gumurdulu Y, Karakose H, et al. Evaluation of the safety and efficacy of sibutramine, orlistat and metformin in the treatment of obesity. Diabetes Obes Metab. 2002;4:4955. Glueck CJ, Fontaine RN, Wang P, et al. Metformin reduces weight, centripital obesity, insulin, leptin, and low-density lipoprotein cholesterol in non diabetic, morbidly obese subjects with body mass index greater than 30. Metabolism. 2001;50:856861. Yang Wenying, Lin Lixiang, Qi Jinwu, et al. The preventive effect of acarbose and metformin on the progression to diabetes mellitus in the IGT population: a 3 year multicenter prospective study. Chin J Endocrinol Metab. 2001;17:131135. Lehtovirta M, Forsn B, Gullstrm M, et al. Metabolic effects of metformin in patients with impaired glucose tolerance. Diabet Med. 2001;18:578583. Hoeger KM, Kochman L, Wixom N, et al. A randomized, 48-week, placebo-controlled trial of intensive lifestyle modification and/or metformin therapy in overweight women with polycystic ovary syndrome: a pilot study. Fertil Steril. 2004;82:421429. Lord JM, Flight IH, Norman RJ. Metformin in polycystic ovary syndrome: systematic review and meta-analysis. BMJ. 2003;327(7421):951953.
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taking high doses of metformin for greater than two months, may show a weight loss benefit. This remains to be proven in larger studies as the subgroup analysis is too small to say definitively What can we conclude about metformin for weight control in a nondiabetic population? While there are benefits to using metformin in nondiabetic populations (e.g., for the prevention type 2 diabetes), there is no compelling evidence to use metfomin to control body weight in nondiabetic populations. A caveat may be found in women with obesity and PCOS on long-term therapy.
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SUMMARY
Metformin is a widely used drug for the treatment of diabetes and the off-label treatment of prediabetes, metabolic syndrome, and insulin resistance. While prevention of diabetes in a high-risk population is seen with the use of metformin, the old standard of lifestyle modification appears to be more efficacious. Metformin does remain a cornerstone of therapy for diabetes and is often used as firstline therapy. Overall, metformin appears to be a relatively weightneutral drug, with some evidence of modest weight loss effect. Metformin appears to mitigate the weight gain seen by other agents used for the treatment of diabetes. At this time, using metformin as a primary weight loss agent in the nondiabetic population appears to be unwarranted in the majority of subpopulations. An exception to this may be women with PCOS.
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ACKNOWLEDGMENT
This article is part of a series of articles being published in Bariatric Times that are based on sessions presented at the Comprehensive Approach to the Treatment of Obesity, by Cedars Sinai Medical Center on October 22, 2010.
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REFERENCES
1. Timar O, Sestier F, Levy E. Metabolic syndrome X: a review. Can J Cardiol. 2000;16:779789. Grundy SM. Hypertriglyceridemia, insulin resistance and the metabolic syndrome. Am J Cardiol. 1999;83(9B):25F29F. Consensus Development Conference on Insulin Resistance. 5-6 November 1997. American Diabetes Association. Diabetes Care. 1998 21:310314. Diabetes Prevention Program Research Group. The Diabetes Prevention Program: baseline characteristics of the randomized cohort. Diabetes Care. 2000;23:16191629. Tankova T. Current indications for metformin therapy. Rom J Intern 15.
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Review
TABLE 1. Metformin and body weight in subjects with diabetes AUTHOR DURATION (MONTHS) NUMBER OF SUBJECTS TREATMENT ARMS MEAN CHANGE IN BODY WEIGHT (KG)
+1.5 +1.9 +3.7 -2.9 +1.6 +4.8 -2.5 +1.9 -1.97 +2.62 -0.6 -1.1 -2.0 +0.1 +0.6
120
1030
metformin diet glibenclamide metformin glibenclamide rosiglitazone metformin pioglitazone metformin glipizide metformin placebo Metformin Placebo Rosiglitazone
Kahn et al. N Engl J Med. 2006 Schernthaner et al. J Clin Endocrinol Metab. 2004 Campbell et al. Diabetes Metab. 1994 Defronzo et al. N Engl J Med. 1995
48
4360
12
1119
12
48
289
6.5
45
TABLE 2. Metformin and body weight in subjects without diabetes: obesity AUTHOR DURATION (MONTHS) NUMBER OF SUBJECTS TREATMENT ARMS MEAN CHANGE IN BODY WEIGHT (KG)
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metformin
-2.0
metformin
-5.9*
*statistically significant
TABLE 3. Metformin and body weight in subjects without diabetes: impaired glucose tolerance DURATION (MONTHS) NUMBER OF SUBJECTS MEAN CHANGE IN BODY WEIGHT (KG)
-2.1 -0.1 -5.6 -0.3* -0.4* -0.7* +0.2* -2.6 -1.2
AUTHOR
TREATMENT ARMS
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3234
metformin placebo intensive lifestyle metformin diet/exercise acarbose control metformin placebo
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