Management of obesity

The main treatment for obesity consists of dieting and physical exercise.[1] Diet programs may produce weight loss over the short term,[2] but maintaining this weight loss is frequently difficult and often requires making exercise and a lower calorie diet a permanent part of an individual's lifestyle.[3][4] Success rates of long-term weight loss maintenance with lifestyle changes are low, ranging from 2 to 20%.[5] Dietary and lifestyle changes are effective in limiting excessive weight gain in pregnancy and improve outcomes for both the mother and the child.[6]

One medication, orlistat (Alli; Xenixal), is current widely available and approved for long term use. Weight loss however is modest with an average of 2.9 kg (6.4 lb) at 1 to 4 years and there is little information on how these drugs affect longer-term complications of obesity.[7] Its use is associated with high rates of gastrointestinal side effects.[7]

The most effective treatment for obesity is bariatric surgery.[8] Surgery for severe obesity is associated with long-term weight loss and decreased overall mortality. One study found a weight loss of between 14% and 25% (depending on the type of procedure performed) at 10 years, and a 29% reduction in all cause mortality when compared to standard weight loss measures.[9] However, due to its cost and the risk of complications, researchers are searching for other effective yet less invasive treatments.

A 2007 review concluded that certain subgroups such as those with type 2 diabetes and women show long term benefits in all cause mortality, while outcomes for men do not seem to be improved with weight loss.[10] A subsequent study found benefits in mortality from intentional weight loss in those who have severe obesity.[11]

Dieting

Main article: Dieting

Diets to promote weight loss are generally divided into four categories: low-fat, low-carbohydrate, low-calorie, and very low calorie.[2] A meta-analysis of six randomized controlled trials found no difference between three of the main diet types (low calorie, low carbohydrate, and low fat), with a 2–4 kilogram (4.4–8.8 lb) weight loss in all studies.[2] At two years these three methods resulted in similar weight loss irrespective of the macronutrients emphasized.[12] High protein diets do not appear to make any difference.[13] A diet high in simple sugars such as those in soft drinks increases weight.[14]

Very low calorie diets provide 200–800 kcal/day, maintaining protein intake but limiting calories from both fat and carbohydrates. They subject the body to starvation and produce an average weekly weight loss of 1.5–2.5 kilograms (3.3–5.5 lb). These diets are not recommended for general use as they are associated with adverse side effects such as loss of lean muscle mass, increased risks of gout, and electrolyte imbalances. People attempting these diets must be monitored closely by a physician to prevent complications.[2]

Exercise

With use, muscles consume energy derived from both fat and glycogen. Due to the large size of leg muscles, walking, running, and cycling are the most effective means of exercise to reduce body fat.[15] Exercise affects macronutrient balance. During moderate exercise, equivalent to a brisk walk, there is a shift to greater use of fat as a fuel.[16][17] To maintain health, the American Heart Association recommends a minimum of 30 minutes of moderate exercise at least 5 days a week.[17]

The Cochrane Collaboration found that exercising alone led to limited weight loss. In combination with diet, however, it resulted in a 1 kilogram weight loss over dieting alone. A 1.5 kilogram (3.3 lb) loss was observed with a greater degree of exercise.[18] Even though exercise as carried out in the general population has only modest effects, a dose response curve is found, and very intense exercise can lead to substantial weight loss. During 20 weeks of basic military training with no dietary restriction, obese military recruits lost 12.5 kg (27.6 lb).[19] High levels of physical activity seem to be necessary to maintain weight loss.[20] A pedometer appears useful for motivation. Over an average of 18-weeks of use physical activity increased by 27% resulting in a 0.38 decreased in BMI.[21]

Signs that encourage the use of stairs as well as community campaigns have been shown to be effective in increasing exercise in a population.[22] The city of Bogota, Colombia for example blocks off 113 kilometers (70 mi) of roads every Sunday and on holidays to make it easier for its citizens to get exercise. These pedestrian zones are part of an effort to combat chronic diseases, including obesity.[23]

In an effort to combat the issue, a primary school in Australia instituted a standing classroom in 2013.[24]

Weight loss programs

Weight loss programs often promote lifestyle changes and diet modification. This may involve eating smaller meals, cutting down on certain types of food, and making a conscious effort to exercise more. These programs also enable people to connect with a group of others who are attempting to lose weight, in the hopes that participants will form mutually motivating and encouraging relationships.[25]

A number of popular programs exist, including Weight Watchers, Overeaters Anonymous, and Jenny Craig. These appear to provide modest weight loss (2.9 kg, 6.4 lb) over dieting on one's own (0.2 kg, 0.4 lb) over a two year period.[26] Internet-based programs appear to be ineffective.[27] The Chinese government has introduced a number of "fat farms" where obese children go for reinforced exercise, and has passed a law which requires students to exercise or play sports for an hour a day at school (see Obesity in China).[28][29]

In a structured setting, 67% of people who lost greater than 10% of their body mass maintained or continued to lose weight one year later.[30] An average maintained weight loss of more than 3 kg (6.6 lb) or 3% of total body mass could be sustained for five years.[31]

In addition to the popular mainstream programs mentioned above, there are a large number of diet products and programs available on the internet. These diet programs may be web based programs, or programs that are downloaded by the dieter. Many of these programs have very large followings and have been available for many years. Due to the nature of these programs it is difficult to determine how many people are actively following the system, or how effective the program is. In many cases these programs are authored by sports or nutrition experts. There are also many social websites that offer weight loss programs. These may be in the form of a free forum or a paid membership. One popular source is the social network Google Plus. On Google Plus, there are many circles that one can join related to weight loss, each with hundreds or even thousands of members. It is of no surprise that people in our age would turn to technology and search for diet solutions on their computers, laptops and smart phones.

Medication

The cardboard packaging of two medications used to treat obesity. Orlistat is shown above under the brand name Xenical in a white package with Roche branding. Sibutramine is below under the brand name Meridia. Orlistat is also available as Alli in the United Kingdom. The A of the Abbott Laboratories logo is on the bottom half of the package.
Orlistat (Xenical) the most commonly used medication to treat obesity and sibutramine (Meridia) a withdrawn medication due to cardiovascular side effects

Several anti-obesity medications are currently approved by the FDA for long term use.[32][33][34] Orlistat reduces intestinal fat absorption by inhibiting pancreatic lipase.

Lorcaserin has been found to be effective in the treatment of obesity with a weight loss of 5.8 kg at one year as opposed to 2.2 kg with placebo[35][36] and it is approved by the Food and Drug Administration for use in the treatment of obesity.[37] Side effects may include serotonin syndrome.[32]

The combination drug phentermine/topiramate (Qsymia) is approved by the FDA as an addition to a reduced-calorie diet and exercise for chronic weight management.[38]

Rimonabant (Acomplia), another drug, had been withdrawn from the market. It worked via a specific blockade of the endocannabinoid system. It has been developed from the knowledge that cannabis smokers often experience hunger, which is often referred to as "the munchies". It had been approved in Europe for the treatment of obesity but has not received approval in the United States or Canada due to safety concerns.[39][40] European Medicines Agency in October 2008 recommended the suspension of the sale of rimonabant as the risk seem to be greater than the benefits.[41] Sibutramine (Meridia), which acts in the brain to inhibit deactivation of the neurotransmitters, thereby decreasing appetite was withdrawn from the UK market in January 2010 and United States and Canadian markets in October 2010 due to cardiovascular concerns.[34][42][43]

Weight loss with these drugs is modest. Over the longer term, average weight loss on orlistat is 2.9 kg (6.4 lb), sibutramine is 4.2 kg (9.3 lb) and rimonabant is 4.7 kg (10.4 lb). Orlistat and rimonabant lead to a reduced incidence of diabetes, and all three drugs have some effect on cholesterol. However, there is little information on how these drugs affect the longer-term complications or outcomes of obesity.[7] In 2010 it was found that sibutramine increases the risk of heart attacks and strokes in people with a history of cardiovascular disease.[44][45]

There are a number of less commonly used medications. Some are only approved for short term use, others are used off-label, and still others are used illegally. Most are appetite suppressants that act on one or more neurotransmitters.[46] Phendimetrazine (Bontril), diethylpropion (Tenuate), and phentermine (Adipex-P) are approved by the FDA for short term use, while bupropion (Wellbutrin), topiramate (Topamax), and zonisamide (Zonegran) are sometimes used off-label.[33] Recombinant human leptin is very effective in those with obesity due to congenital complete leptin deficiency via decreasing energy intake and possibly increases energy expenditure. This condition is, however, rare and this treatment is not effective for inducing weight loss in the majority of people with obesity. It is being investigated to determine whether or not it helps with weight loss maintenance.[47]

The usefulness of certain drugs depends upon the comorbidities present. Metformin (Glucophage) is preferred in overweight diabetics, as it may lead to mild weight loss in comparison to sulfonylureas or insulin.[48] The thiazolidinediones, on the other hand, may cause weight gain, but decrease central obesity.[49] Diabetics also achieve modest weight loss with fluoxetine (Prozac), orlistat and sibutramine over 12–57 weeks. Preliminary evidence has however found higher number of cardiovascular events in people taking sibutramine verses control (11.4% vs. 10.0%).[50] The long-term health benefits of these treatments remain unclear.[51]

Fenfluramine and dexfenfluramine were withdrawn from the market in 1997,[33] while ephedrine (found in the traditional Chinese herbal medicine má huáng made from the Ephedra sinica) was removed from the market in 2004.[52] Dexamphetamines are not approved by the FDA for the treatment of obesity[53] due to concerns regarding addiction and abuse potential.[33] The use of these drugs is not recommended due to potential side effects.[54] However, people do occasionally use these drugs illegally.[55]

Surgery

Main article: Bariatric surgery

Bariatric surgery ("weight loss surgery") is the use of surgical intervention in the treatment of obesity. As every operation may have complications, surgery is only recommended for severely obese people (BMI > 40) who have failed to lose weight following dietary modification and pharmacological treatment. Weight loss surgery relies on various principles: the two most common approaches are reducing the volume of the stomach (e.g. by adjustable gastric banding and vertical banded gastroplasty), which produces an earlier sense of satiation, and reducing the length of bowel that comes into contact with food (gastric bypass surgery), which directly reduces absorption. Band surgery is reversible, while bowel shortening operations are not. Some procedures can be performed laparoscopically. Complications from weight loss surgery are frequent.[56]

Surgery for severe obesity is associated with long-term weight loss and decreased overall mortality. One study found a weight loss of between 14% and 25% (depending on the type of procedure performed) at 10 years, and a 29% reduction in all cause mortality when compared to standard weight loss measures.[9] A marked decrease in the risk of diabetes mellitus, cardiovascular disease and cancer has also been found after bariatric surgery.[57][58] Marked weight loss occurs during the first few months after surgery, and the loss is sustained in the long term. In one study there was an unexplained increase in deaths from accidents and suicide, but this did not outweigh the benefit in terms of disease prevention.[58] When the two main techniques are compared, gastric bypass procedures are found to lead to 30% more weight loss than banding procedures one year after surgery.[59]

Ileojejunal bypass, in which the digestive tract is rerouted to bypass the small intestine, was an experimental surgery designed as a remedy for morbid obesity.

The effects of liposuction on obesity are less well determined. Some small studies show benefits[60] while others show none.[61] A treatment involving the placement of an intragastric balloon via gastroscopy has shown promise. One type of balloon led to a weight loss of 5.7 BMI units over 6 months or 14.7 kg (32.4 lb). Regaining lost weight is common after removal, however, and 4.2% of people were intolerant of the device.[62]

An implantable nerve simulator which improves the feeling of fullness was approved by the FDA in 2015.[63]

Clinical protocols

Much of the Western world has created clinical practice guidelines in an attempt to address rising rates of obesity. Australia,[64] Canada,[1] the European Union,[65] and the United States[66] have all published statements since 2004.

In a clinical practice guideline by the American College of Physicians, the following five recommendations are made:[66]

  1. People with a BMI of over 30 should be counseled on diet, exercise and other relevant behavioral interventions, and set a realistic goal for weight loss.
  2. If these goals are not achieved, pharmacotherapy can be offered. The person needs to be informed of the possibility of side-effects and the unavailability of long-term safety and efficacy data.
  3. Drug therapy may consist of sibutramine, orlistat, phentermine, diethylpropion, fluoxetine, and bupropion. For more severe cases of obesity, stronger drugs such as amphetamine and methamphetamine may be used on a selective basis. Evidence is not sufficient to recommend sertraline, topiramate, or zonisamide.
  4. In people with a BMI over 40 who fail to achieve their weight loss goals (with or without medication) and who develop obesity-related complications, referral for bariatric surgery may be indicated. The person needs to be aware of the potential complications.
  5. Those requiring bariatric surgery should be referred to high-volume referral centers, as the evidence suggests that surgeons who frequently perform these procedures have fewer complications.

A clinical practice guideline by the US Preventive Services Task Force (USPSTF) concluded that the evidence is insufficient to recommend for or against routine behavioral counseling to promote a healthy diet in unselected people in primary care settings, but that intensive behavioral dietary counseling is recommended in those with hyperlipidemia and other known risk factors for cardiovascular and diet-related chronic disease. Intensive counseling can be delivered by primary care clinicians or by referral to other specialists, such as nutritionists or dietitians.[67][68]

Canada developed and published evidence-based practice guidelines in 2006. The guidelines attempt to address the prevention and management of obesity at both the individual and population levels in both children and adults.[1] The European Union published clinical practice guidelines in 2008 in an effort to address the rising rates of obesity in Europe.[65] Australia came out with practice guidelines in 2004.[64]

Research

Temporary, controllable gastric pseudo-bezoars (swallowable, swellable foreign bodies in the stomach meant to reduce gastric volume from inside the organ) are being tested.[69] Treatment with naltrexone plus bupropion in a phase three trial resulted in a weight lose of 5–6% versus 1% for a placebo.[70]

References

  1. ↑ 1.0 1.1 1.2 Lau DC, Douketis JD, Morrison KM, Hramiak IM, Sharma AM, Ur E; Douketis; Morrison; Hramiak; Sharma; Ur; Obesity Canada Clinical Practice Guidelines Expert Panel (April 2007). "2006 Canadian clinical practice guidelines on the management and prevention of obesity in adults and children [summary]". CMAJ 176 (8): S1–13. doi:10.1503/cmaj.061409. PMC 1839777. PMID 17420481.
  2. ↑ 2.0 2.1 2.2 2.3 Strychar I (January 2006). "Diet in the management of weight loss". CMAJ 174 (1): 56–63. doi:10.1503/cmaj.045037. PMC 1319349. PMID 16389240.
  3. ↑ Shick SM, Wing RR, Klem ML, McGuire MT, Hill JO, Seagle H; Wing; Klem; McGuire; Hill; Seagle (April 1998). "Persons successful at long-term weight loss and maintenance continue to consume a low-energy, low-fat diet". J Am Diet Assoc 98 (4): 408–13. doi:10.1016/S0002-8223(98)00093-5. PMID 9550162.
  4. ↑ Tate DF, Jeffery RW, Sherwood NE, Wing RR; Jeffery; Sherwood; Wing (1 April 2007). "Long-term weight losses associated with prescription of higher physical activity goals. Are higher levels of physical activity protective against weight regain?". Am. J. Clin. Nutr. 85 (4): 954–9. PMID 17413092.
  5. ↑ Wing, Rena R; Phelan, Suzanne (1 July 2005). "Science-Based Solutions to Obesity: What are the Roles of Academia, Government, Industry, and Health Care? Proceedings of a symposium, Boston, Massachusetts, USA, 10–11 March 2004 and Anaheim, California, USA, 2 October 2004". Am. J. Clin. Nutr. 82 (1 Suppl): 207S–273S. PMID 16002825.
  6. ↑ Thangaratinam, S; Rogozinska, E; Jolly, K; Glinkowski, S; Roseboom, T; Tomlinson, JW; Kunz, R; Mol, BW; Coomarasamy, A; Khan, KS (May 16, 2012). "Effects of interventions in pregnancy on maternal weight and obstetric outcomes: meta-analysis of randomised evidence.". BMJ (Clinical research ed.) 344: e2088. doi:10.1136/bmj.e2088. PMC 3355191. PMID 22596383.
  7. ↑ 7.0 7.1 7.2 Rucker D, Padwal R, Li SK, Curioni C, Lau DC; Padwal; Li; Curioni; Lau (2007). "Long term pharmacotherapy for obesity and overweight: Updated meta-analysis". BMJ 335 (7631): 1194–99. doi:10.1136/bmj.39385.413113.25. PMC 2128668. PMID 18006966.
  8. ↑ Colquitt, JL; Pickett, K; Loveman, E; Frampton, GK (Aug 8, 2014). "Surgery for weight loss in adults.". The Cochrane database of systematic reviews 8: CD003641. doi:10.1002/14651858.CD003641.pub4. PMID 25105982.
  9. ↑ 9.0 9.1 Sjöström L; Narbro K; Sjöström CD et al. (August 2007). "Effects of bariatric surgery on mortality in Swedish obese subjects". N. Engl. J. Med. 357 (8): 741–52. doi:10.1056/NEJMoa066254. PMID 17715408.
  10. ↑ Poobalan AS, Aucott LS, Smith WC, Avenell A, Jung R, Broom J; Aucott; Smith; Avenell; Jung; Broom (November 2007). "Long-term weight loss effects on all cause mortality in overweight/obese populations". Obes Rev 8 (6): 503–13. doi:10.1111/j.1467-789X.2007.00393.x. PMID 17949355.
  11. ↑ Peeters A; O'Brien PE; Laurie C et al. (December 2007). "Substantial intentional weight loss and mortality in the severely obese". Ann. Surg. 246 (6): 1028–33. doi:10.1097/SLA.0b013e31814a6929. PMID 18043106.
  12. ↑ Sacks FM; Bray GA; Carey VJ et al. (February 2009). "Comparison of weight-loss diets with different compositions of fat, protein, and carbohydrates". N. Engl. J. Med. 360 (9): 859–73. doi:10.1056/NEJMoa0804748. PMC 2763382. PMID 19246357.
  13. ↑ Schwingshackl, L; Hoffmann, G (Apr 15, 2013). "Long-term effects of low-fat diets either low or high in protein on cardiovascular and metabolic risk factors: a systematic review and meta-analysis". Nutrition journal 12: 48. doi:10.1186/1475-2891-12-48. PMC 3636027. PMID 23587198.
  14. ↑ Te Morenga, L; Mallard, S; Mann, J (Jan 15, 2012). "Dietary sugars and body weight: systematic review and meta-analyses of randomised controlled trials and cohort studies.". BMJ (Clinical research ed.) 346: e7492. doi:10.1136/bmj.e7492. PMID 23321486.
  15. ↑ Gwinup G (1987). "Weight loss without dietary restriction: Efficacy of different forms of aerobic exercise". Am J Sports Med 15 (3): 275–9. doi:10.1177/036354658701500317. PMID 3618879.
  16. ↑ Sahlin K, Sallstedt EK, Bishop D, Tonkonogi M; Sallstedt; Bishop; Tonkonogi (December 2008). "Turning down lipid oxidation during heavy exercise—what is the mechanism?". J. Physiol. Pharmacol. 59 Suppl 7: 19–30. PMID 19258655.
  17. ↑ 17.0 17.1 Haskell WL; Lee IM; Pate RR et al. (August 2007). "Physical activity and public health: updated recommendation for adults from the American College of Sports Medicine and the American Heart Association". Circulation 116 (9): 1081–93. doi:10.1161/CIRCULATIONAHA.107.185649. PMID 17671237.
  18. ↑ Shaw K, Gennat H, O'Rourke P, Del Mar C; Gennat; O'Rourke; Del Mar (2006). "Exercise for overweight or obesity". Cochrane database of systematic reviews (Online) (4): CD003817. doi:10.1002/14651858.CD003817.pub3. PMID 17054187.
  19. ↑ Lee L, Kumar S, Leong LC; Kumar; Leong (February 1994). "The impact of five-month basic military training on the body weight and body fat of 197 moderately to severely obese Singaporean males aged 17 to 19 years". Int. J. Obes. Relat. Metab. Disord. 18 (2): 105–9. PMID 8148923.
  20. ↑ Bessesen DH (June 2008). "Update on obesity". J. Clin. Endocrinol. Metab. 93 (6): 2027–34. doi:10.1210/jc.2008-0520. PMID 18539769.
  21. ↑ Bravata DM; Smith-Spangler C; Sundaram V et al. (November 2007). "Using pedometers to increase physical activity and improve health: a systematic review". JAMA: the Journal of the American Medical Association 298 (19): 2296–304. doi:10.1001/jama.298.19.2296. PMID 18029834.
  22. ↑ Kahn EB; Ramsey LT; Brownson RC et al. (May 2002). "The effectiveness of interventions to increase physical activity. A systematic review". Am J Prev Med 22 (4 Suppl): 73–107. doi:10.1016/S0749-3797(02)00434-8. PMID 11985936.
  23. ↑ "www.paho.org". Pan American Health Organization. Retrieved January 10, 2009.
  24. ↑ "World's first standing classroom launched in Australia - The Times of India". The Times Of India.
  25. ↑ Baron M (November 2004). "Commercial weight-loss programs". Health Care Food Nutr Focus 21 (11): 8–9. PMID 15559885.
  26. ↑ Heshka S; Anderson JW; Atkinson RL et al. (April 2003). "Weight loss with self-help compared with a structured commercial program: a randomized trial". JAMA 289 (14): 1792–8. doi:10.1001/jama.289.14.1792. PMID 12684357.
  27. ↑ Tsai AG, Wadden TA; Wadden (January 2005). "Systematic review: an evaluation of major commercial weight loss programs in the United States". Annals of Internal Medicine 142 (1): 56–66. doi:10.7326/0003-4819-142-1-200501040-00012. PMID 15630109.
  28. ↑ Hewitt, Duncan (May 23, 2000). "China battles obesity". BBC. Retrieved August 8, 2009.
  29. ↑ MacLeod, Calum (August 1, 2007). "Obesity of China's kids stuns officials". USA Today. Retrieved August 8, 2009.
  30. ↑ Weiss EC, Galuska DA, Kettel Khan L, Gillespie C, Serdula MK; Galuska; Kettel Khan; Gillespie; Serdula (July 2007). "Weight regain in U.S. adults who experienced substantial weight loss, 1999–2002". Am J Prev Med 33 (1): 34–40. doi:10.1016/j.amepre.2007.02.040. PMID 17572309.
  31. ↑ Anderson JW, Konz EC, Frederich RC, Wood CL; Konz; Frederich; Wood (1 November 2001). "Long-term weight-loss maintenance: A meta-analysis of US studies". Am. J. Clin. Nutr. 74 (5): 579–84. PMID 11684524.
  32. ↑ 32.0 32.1 "FDA approves Belviq to treat some overweight or obese adults". FDA. June 27, 2012. Retrieved 8 July 2012.
  33. ↑ 33.0 33.1 33.2 33.3 "WIN – Publication – Prescription Medications for the Treatment of Obesity". National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). National Institutes of Health. Retrieved January 14, 2009.
  34. ↑ 34.0 34.1 "www.fda.gov".
  35. ↑ Astrup, A. (Jul 2010). "Drug management of obesity--efficacy versus safety". N Engl J Med 363 (3): 288–90. doi:10.1056/NEJMe1004076. PMID 20647205.
  36. ↑ Bays, HE (March 2011). "Lorcaserin: drug profile and illustrative model of the regulatory challenges of weight-loss drug development.". Expert review of cardiovascular therapy 9 (3): 265–77. doi:10.1586/erc.10.22. PMID 21438803.
  37. ↑ Healy, Melissa; For, / (June 27, 2012). "FDA approves lorcaserin, first weight-loss drug OK'd since 1999". Los Angeles Times.
  38. ↑ "FDA approves weight-management drug Qsymia". Food and Drug Administration. July 17, 2012.
  39. ↑ "Anti-obesity drug no magic bullet". Canadian Broadcasting Corporation. January 2, 2007. Retrieved 2008-09-19.
  40. ↑ "FDA Briefing Document NDA 21-888 Zimulti (rimonabant) Tablets, 20 mg Sanofi Aventis Advisory Committee" (PDF). Food and Drug Administration. June 13, 2007. Retrieved 2008-09-19.
  41. ↑ "www.emea.europa.eu".
  42. ↑ "Abbott Laboratories Voluntarily Withdraws Weight-loss Drug Sibutramine (Meridia) from the Canadian Market - Health Canada Information Update 2010-10-08".
  43. ↑ "www.nice.org.uk".
  44. ↑ "Meridia (sibutramine hydrochloride): Follow-Up to an Early Communication about an Ongoing Safety Review".
  45. ↑ James WP; Caterson ID; Coutinho W et al. (September 2010). "Effect of sibutramine on cardiovascular outcomes in overweight and obese subjects". N. Engl. J. Med. 363 (10): 905–17. doi:10.1056/NEJMoa1003114. PMID 20818901.
  46. ↑ Li Z; Maglione M; Tu W et al. (April 2005). "Meta-analysis: pharmacologic treatment of obesity". Annals of Internal Medicine 142 (7): 532–46. doi:10.7326/0003-4819-142-7-200504050-00012. PMID 15809465.
  47. ↑ Kelesidis T, Kelesidis I, Chou S, Mantzoros CS; Kelesidis; Chou; Mantzoros (January 2010). "Narrative review: the role of leptin in human physiology: emerging clinical applications". Annals of Internal Medicine 152 (2): 93–100. doi:10.1059/0003-4819-152-2-201001190-00008 (inactive 2015-02-01). PMC 2829242. PMID 20083828.
  48. ↑ UK Prospective Diabetes Study (UKPDS) Group (1998). "Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34)". Lancet 352 (9131): 854–65. doi:10.1016/S0140-6736(98)07037-8. PMID 9742977.
  49. ↑ Fonseca V (2003). "Effect of thiazolidinediones on body weight in patients with diabetes mellitus". Am. J. Med. 115 Suppl 8A (8): 42S–48S. doi:10.1016/j.amjmed.2003.09.005. PMID 14678865.
  50. ↑ "Early Communication about an Ongoing Safety Review of Meridia (sibutramine hydrochloride)". FDA. Retrieved Nov 23, 2009.
  51. ↑ Norris SL, Zhang X, Avenell A, Gregg E, Schmid CH, Lau J; Zhang; Avenell; Gregg; Schmid; Lau (2005). "Pharmacotherapy for weight loss in adults with type 2 diabetes mellitus". Cochrane database of systematic reviews (Online) (1): CD004096. doi:10.1002/14651858.CD004096.pub2. PMID 15674929.
  52. ↑ Rados C (2004). "Ephedra ban: no shortage of reasons". FDA Consum 38 (2): 6–7. PMID 15101356.
  53. ↑ Boss, Olivier; Karl G. Hofbauer (2004). Pharmacotherapy of obesity: options and alternatives. Boca Raton: CRC Press. p. 286. ISBN 0-415-30321-4. Retrieved January 14, 2009.
  54. ↑ Flanagan CM, Kaesberg JL, Mitchell ES, Ferguson MA, Haigney MC; Kaesberg; Mitchell; Ferguson; Haigney (August 2008). "Coronary artery aneurysm and thrombosis following chronic ephedra use". Int. J. Cardiol. 139 (1): e11–3. doi:10.1016/j.ijcard.2008.06.081. PMID 18718687.
  55. ↑ Cohen PA, McCormick D, Casey C, Dawson GF, Hacker KA; McCormick; Casey; Dawson; Hacker (December 2007). "Imported Compounded Diet Pill Use Among Brazilian Women Immigrants in the United States". J Immigr Minor Health 11 (3): 229–36. doi:10.1007/s10903-007-9099-x. PMID 18066718.
  56. ↑ Encinosa WE, Bernard DM, Chen CC, Steiner CA; Bernard; Chen; Steiner (2006). "Healthcare utilization and outcomes after bariatric surgery". Medical care 44 (8): 706–12. doi:10.1097/01.mlr.0000220833.89050.ed. PMID 16862031.
  57. ↑ Sjöström L; Narbro K; Sjöström CD et al. (2007). "Effects of bariatric surgery on mortality in Swedish obese subjects". N. Engl. J. Med. 357 (8): 741–52. doi:10.1056/NEJMoa066254. PMID 17715408.
  58. ↑ 58.0 58.1 Adams TD; Gress RE; Smith SC et al. (2007). "Long-term mortality after gastric bypass surgery". N. Engl. J. Med. 357 (8): 753–61. doi:10.1056/NEJMoa066603. PMID 17715409.
  59. ↑ Tice JA, Karliner L, Walsh J, Petersen AJ, Feldman MD; Karliner; Walsh; Petersen; Feldman (October 2008). "Gastric banding or bypass? A systematic review comparing the two most popular bariatric procedures". Am. J. Med. 121 (10): 885–93. doi:10.1016/j.amjmed.2008.05.036. PMID 18823860.
  60. ↑ Giugliano G; Nicoletti G; Grella E et al. (April 2004). "Effect of liposuction on insulin resistance and vascular inflammatory markers in obese women". Br J Plast Surg 57 (3): 190–4. doi:10.1016/j.bjps.2003.12.010. PMID 15006519.
  61. ↑ Klein S; Fontana L; Young VL et al. (June 2004). "Absence of an effect of liposuction on insulin action and risk factors for coronary heart disease". N. Engl. J. Med. 350 (25): 2549–57. doi:10.1056/NEJMoa033179. PMID 15201411.
  62. ↑ Imaz I, Martínez-Cervell C, García-Alvarez EE, Sendra-Gutiérrez JM, González-Enríquez J; Martínez-Cervell; García-Alvarez; Sendra-Gutiérrez; González-Enríquez (July 2008). "Safety and effectiveness of the intragastric balloon for obesity. A meta-analysis". Obes Surg 18 (7): 841–6. doi:10.1007/s11695-007-9331-8. PMID 18459025.
  63. ↑ "FDA approves first-of-kind device to treat obesity". fda.gov. January 14, 2015. Retrieved 18 January 2015.
  64. ↑ 64.0 64.1 "Obesity Guidelines Website". Australian Government Department of Health and Ageing. Retrieved Oct 25, 2009.
  65. ↑ 65.0 65.1 Tsigosa Constantine; Hainer, Vojtech; Basdevant, Arnaud; Finer, Nick; Fried, Martin; Mathus-Vliegen, Elisabeth; Micic, Dragan; Maislos, Maximo et al. (April 2008). "Management of Obesity in Adults: European Clinical Practice Guidelines". The European Journal of Obesity 1 (2): 106–16. doi:10.1159/000126822. PMID 20054170.
  66. ↑ 66.0 66.1 Snow V, Barry P, Fitterman N, Qaseem A, Weiss K; Barry; Fitterman; Qaseem; Weiss; Clinical Efficacy Assessment Subcommittee of the American College of Physicians (2005). "Pharmacologic and surgical management of obesity in primary care: A clinical practice guideline from the American College of Physicians". Annals of Internal Medicine 142 (7): 525–31. doi:10.7326/0003-4819-142-7-200504050-00011. PMID 15809464. Fulltext.
  67. ↑ U.S. Preventive Services Task Force (June 2003). "Behavioral counseling in primary care to promote a healthy diet: recommendations and rationale". Am Fam Physician 67 (12): 2573–6. PMID 12825847.
  68. ↑ Pignone MP; Ammerman A; Fernandez L et al. (2003). "Counseling to promote a healthy diet in adults: A summary of the evidence for the U.S. Preventive Services Task Force". American Journal of Preventive Medicine 24 (1): 75–92. doi:10.1016/S0749-3797(02)00580-9. PMID 12554027.
  69. ↑ Mintchev MP, Deneva MG, Aminkov BI, Fattouche M, Yadid-Pecht O, Bray RC; Deneva; Aminkov; Fattouche; Yadid-Pecht; Bray (1 February 2010). "Pilot study of temporary controllable gastric pseudobezoars for dynamic non-invasive gastric volume reduction". Physiol. Meas. 31 (2): 131–44. Bibcode:2010PhyM...31..131M. doi:10.1088/0967-3334/31/2/001. PMID 20009188.
  70. ↑ "Effect of naltrexone plus bupropion on weight loss in overweight and obese adults (COR-I): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial : The Lancet".