Anti-obesity medication or weight loss drugs are all pharmacological agents that reduce or control weight. These drugs alter one of the fundamental processes of the human body, weight regulation, by altering either appetite, or absorption of calories. The main treatment modalities for overweight and obese individuals remain dieting and physical exercise.
In the United States only one anti-obesity medication orlistat (Xenical) is currently approved by the FDA for long term use. It reduces intestinal fat absorption by inhibiting pancreatic lipase. Rimonabant (Acomplia), a second drug, works 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. The European Medicines Agency in October 2008 recommended the suspension of the sale of rimonabant as the risks seem to be greater than the benefits. Sibutramine (Meridia), which acts in the brain to inhibit deactivation of the neurotransmitters, thereby decreasing appetite was withdrawn from the United States and Canadian markets in October 2010 due to cardiovascular concerns.
- 1 Mechanisms of action
- 2 History
- 3 Contemporary anti-obesity drugs
- 4 Alternative medicine
- 5 Side effects
- 6 Limitations of current knowledge
- 7 Future developments
- 8 See also
- 9 References
- 10 Further reading
- 11 External links
Mechanisms of action
Current and potential anti-obesity drugs may operate through one or more of the following mechanisms:
- Appetite suppression-Catecholamines and their derivatives (such as phentermine and other amphetamine-based drugs) are the main tools used for this, although other classes of drugs such as anti-depressants and mood stabilizers have been anecdotally used for appetite suppression (see: bupropion and topiramate). Drugs blocking the cannabinoid receptors may be a future strategy for appetite suppression.
- Increase of the body's metabolism.
- Interference with the body's ability to absorb specific nutrients in food. For example, Orlistat (also known as Xenical and Alli) blocks fat breakdown and thereby prevents fat absorption. The OTC fiber supplements glucomannan and guar gum have been used for the purpose of inhibiting digestion and lowering caloric absorption
Anorectics are primarily intended to suppress the appetite, but most of the drugs in this class also act as stimulants (e.g., dexedrine), and patients have abused drugs "off label" to suppress appetite (e.g. digoxin).
The first described attempts at producing weight loss are those of Soranus of Ephesus, a Greek physician, in the second century AD. He prescribed elixirs of laxatives and purgatives, as well as heat, massage, and exercise. This remained the mainstay of treatment for well over a thousand years. It was not until the 1920s and 1930s that new treatments began to appear. Based on its effectiveness for hypothyroidism, thyroid hormone became a popular treatment for obesity in euthyroid people. It had a modest effect but produced the symptoms of hyperthyroidism as a side effect, such as palpitations and difficulty sleeping. 2,4-Dinitrophenol (DNP) was introduced in 1933; this worked by uncoupling the biological process of oxidative phosphorylation in mitochondria, causing them to produce heat instead of ATP. The most significant side effect was a sensation of warmth, frequently with sweating. Overdose, although rare, lead to a rise in body temperature and, ultimately, fatal hyperthermia. By the end of 1938 DNP had fallen out of use because the FDA had become empowered to put pressure on manufacturers, who voluntarily withdrew it from the market.
Amphetamines (marketed as Benzedrine) became popular for weight loss during the late 1930s. They worked primarily by suppressing appetite, and had other beneficial effects such as increased alertness. Use of amphetamines increased over the subsequent decades, including Obetrol and culminating in the "rainbow pill" regime. This was a combination of multiple pills, all thought to help with weight loss, taken throughout the day. Typical regimens included stimulants, such as amphetamines, as well as thyroid hormone, diuretics, digitalis, laxatives, and often a barbiturate to suppress the side effects of the stimulants. In 1967/1968 a number of deaths attributed to diet pills triggered a Senate investigation and the gradual implementation of greater restrictions on the market. This culminating in 1979 with the FDA banning the use of amphetamines, then the most effective of the diet drugs, in diet pills.
Meanwhile, phentermine had been FDA approved in 1959 and fenfluramine in 1973. The two were no more popular than other drugs until in 1992 a researcher reported that when combined the two caused a 10% weight loss which was maintained for more than two years. Fen-phen was born and rapidly became the most commonly prescribed diet medication. Dexfenfluramine (Redux) was developed in the mid-1990s as an alternative to fenfluramine with less side-effects, and received regulatory approval in 1996. However, this coincided with mounting evidence that the combination could cause valvular heart disease in up to 30% of those who had taken it, leading to withdrawal of Fen-phen and dexfenfluramine from the market in September 1997.
Contemporary anti-obesity drugs
Some patients find that diet and exercise is not a viable option; for these patients, anti-obesity drugs can be a last resort. Some prescription weight loss drugs are stimulants, which are recommended only for short-term use, and thus are of limited usefulness for extremely obese patients, who may need to reduce weight over months or years.
Orlistat (Xenical) reduces intestinal fat absorption by inhibiting pancreatic lipase. Some side-effects of using Orlistat include frequent, oily bowel movements (steatorrhea). But if fat in the diet is reduced, symptoms often improve. Originally available only by prescription, it was approved by the FDA for over-the-counter sale in February 2007. On 26 May 2010, the U.S. Food and Drug Administration (FDA) has approved a revised label for Xenical to include new safety information about cases of severe liver injury that have been reported rarely with the use of this medication. Of the 40 million users of Orlistat worldwide, 13 cases of severe liver damage have been reported.
Lorcaserin (Belviq) was approved June 28, 2012 for obesity with other co-morbidities. The average weight loss by study participants was modest, but the most common side effects of the drug are considered benign.
An excerpt from the Bloom 1 Study conducted by Arena Pharmaceuticals and later submitted for FDA approval:
At the end of Year 1 of the BLOOM trial, using Intent-to-Treat with Last Observation Carried Forward analysis (ITT-LOCF), the proportion of patients achieving at least 5% body weight loss in the lorcaserin group (47.5%) was more than twice that achieved by the placebo group (20.3%). Nearly three times as many patients achieved at least 10% weight loss in the lorcaserin group (22.6%) than in the placebo group (7.7%). Lorcaserin patients who completed the first year of the trial according to the protocol lost an average of 8.2% of their baseline weight, or approximately 18 pounds, at the end of Year 1 as compared to approximately 7 pounds in the placebo group. In Year 2, patients who continued to take lorcaserin were significantly better able to maintain their Year 1 weight loss than those who were switched to placebo.
In Year 1, lorcaserin caused significant decreases in waist circumference, BMI, glycemic parameters, high-sensitivity C-reactive protein, and fibrinogen levels compared to placebo. Total cholesterol, LDL cholesterol and triglyceride levels at Year 1 were significantly lower in the lorcaserin group than in the placebo group. Lorcaserin did not increase heart rate or blood pressure; rather, heart rate, systolic blood pressure and diastolic blood pressure decreased slightly but significantly with lorcaserin treatment compared to placebo. Quality of life, measured by the Impact of Weight on Quality of Life-Lite questionnaire, improved in both treatment groups, with a greater improvement in the lorcaserin group than in the placebo group.
At the end of Year 1, 55.4% of patients in the lorcaserin group and 45.1% of patients in the placebo group remained enrolled in the study, and 7.1% and 6.7% of patients, respectively, discontinued the study due to an adverse event. Among the most frequent adverse events reported with lorcaserin were headache (18.0% vs. 11.0%, lorcaserin vs. placebo); dizziness (8.2% vs. 3.8%); and nausea (7.5% vs. 5.4%). The rates of serious adverse events were similar in both treatment groups. The rates of depression and the incidence of anxiety and suicidal thoughts were low in both treatment groups. Lorcaserin caused no significant increase compared to placebo in the incidence of new cardiac valvulopathy.
Sibutramine (Reductil or Meridia) is an anorectic or appetite suppressant, reducing the desire to eat. Sibutramine may increase blood pressure and may cause dry mouth, constipation, headache, and insomnia.
In the past, it was noted by the US that Meridia was a harmless drug for fighting obesity. The US District Court of the Northern District of Ohio rejected 113 cases complaining about the negative effects of the drug, stating that the clients lacked supporting facts and that the representatives involved were not qualified enough.
Sibutramine has been withdrawn from the market in the United States, the UK, the EU, Australia, Canada, Hong Kong and Colombia. Its risks (non-life-threatening myocardial infarction and stroke) have been shown to outweigh the benefits.
Rimonabant (Acomplia) is a recently developed anti-obesity medication. It is cannabinoid (CB1) receptor antagonist that acts centrally on the brain thus decreasing appetite. It may also act peripherally by increasing thermogenesis and therefore increasing energy expenditure.
Weight loss with Rimonabant however has not been shown to be greater than other available weight-loss medication. Due to safety concerns, primarily psychiatric in nature, the drug has not received approval in the United States or Canada, either as an anti-obesity treatment or as a smoking-cessation drug.
Sanofi-Aventis has received approval to market Rimonabant as a prescription anti-obesity drug in the European Union, subject to some restrictions. However, in October 2008, the European Medicines Agency (EMEA) recommended that Acomplia no longer be available in UK. One month later, Sanofi-Aventis decided it would no longer study rimonabant for any indication.[clarification needed]
In people with Diabetes mellitus type 2, the drug metformin (Glucophage) can reduce weight. Metformin limits the amount of glucose that is produced by the liver as well as increases muscle consumption of glucose.
Exenatide (Byetta) is a long-acting analogue of the hormone GLP-1, which the intestines secrete in response to the presence of food. Among other effects, GLP-1 delays gastric emptying and promotes a feeling of satiety. Some obese people are deficient in GLP-1, and dieting reduces GLP-1 further. Byetta is currently available as a treatment for Diabetes mellitus type 2. Some, but not all, patients find that they lose substantial weight when taking Byetta. Drawbacks of Byetta include that it must be injected subcutaneously twice daily, and that it causes severe nausea in some patients, especially when therapy is initiated. Byetta is recommended only for patients with Type 2 Diabetes. A somewhat similar drug, Symlin, is currently available for treating diabetes and is in testing for treating obesity in non-diabetics.
|This section does not cite any references or sources. (February 2015)|
Pramlintide (Symlin) is a synthetic analogue of the hormone Amylin, which in normal people is secreted by the pancreas in response to eating. Among other effects, Amylin delays gastric emptying and promotes a feeling of satiety. Many diabetics are deficient in Amylin. Currently, Symlin is only approved to be used along with insulin by Type 1 and Type 2 diabetics. However, Symlin is currently being tested in non-diabetics as a treatment for obesity. A drawback is that Symlin must be injected at mealtimes.
Other weight loss drugs have also been associated with medical complications, such as fatal pulmonary hypertension and heart valve damage due to Redux and Fen-phen, and hemorrhagic stroke due phenylpropanolamine. Many of these substances are related to amphetamine.
Unresearched nonprescription products or programs for weight loss are heavily promoted by mail and print advertising and on the internet. The US Food and Drug Administration recommends caution with use of these products, since many of the claims of safety and effectiveness are unsubstantiated. Individuals with anorexia nervosa and some athletes try to control body weight with laxatives, diet pills or diuretic drugs, although these generally have no impact on body fat. Products that work as a laxative can cause the blood's potassium level to drop, which may cause heart and/or muscle problems. Pyruvate is a popular product that may result in a small amount of weight loss. However, pyruvate, which is found in red apples, cheese, and red wine, has not been thoroughly studied and its weight loss potential has not been scientifically established.
The combination of phentermine and topiramate, brand name Qsymia (formerly Qnexa) was approved by the U.S. FDA on July 17, 2012, as an obestity treatment complementary to a diet and exercise regimen.
|Conjugated linoleic acid||Helps reduce obesity||Ineffective|
|ECA Stack||weight loss; athletic performance||Modest short term weight loss; ineffective in long term||possible adverse effects on the mental, digestive, and nervous systems; heart palpitations|
Some anti-obesity drugs can have severe, even, lethal side effects, fen-phen being a famous example. Fen-phen was reported through the FDA to cause abnormal echocardiograms, heart valve problems, and rare valvular diseases. One of, if not the first, to sound alarms was Sir Arthur MacNalty, Chief Medical Officer (United Kingdom). As early as the 1930s, he warned against the use of dinitrophenol as an anti-obesity medication and the injudicious and/or medically unsupervised use of thyroid hormone to achieve weight reduction. The side effects are often associated with the medication's mechanism of action. In general, stimulants carry a risk of high blood pressure, faster heart rate, palpitations, closed-angle glaucoma, drug addiction, restlessness, agitation, and insomnia.
Another drug, orlistat, blocks absorption of dietary fats, and as a result may cause oily spotting bowel movements (steatorrhea), oily stools, stomach pain, and flatulence. A similar medication designed for patients with Type 2 diabetes is Acarbose; which partially blocks absorption of carbohydrates in the small intestine, and produces similar side effects including stomach pain and flatulence.
Limitations of current knowledge
|This section does not cite any references or sources. (February 2015)|
The limitation of drugs for obesity is that we do not fully understand the neural basis of appetite and how to modulate it. Appetite is clearly a very important instinct to promote survival. Arguably any drug that would abolish appetite may carry a high mortality risk and may be unsuitable for clinical use.
Because the human body uses various chemicals and hormones to protect its stores of fat (a reaction probably useful to our ancestors when food was scarce in the past,) there has not yet been found a 'silver bullet', or a way to completely circumvent this natural habit of protecting excess food stores. Because of this, anti-obesity drugs are not a practical long-term solution for people who are overweight.
In order to circumvent the number of feedback mechanisms that prevent most monotherapies from producing sustained large amounts of weight loss, it has been hypothesized that combinations of drugs may be more effective by targeting multiple pathways and possibly inhibiting feedback pathways that work to cause a plateau in weight loss. This was evidenced by the success of the combination of phentermine and fenfluramine or dexfenfluramine, popularly referred to phen-fen, in producing significant weight loss but fenfluramine and dexfenfluramine were pulled from the market due to safety fears regarding a potential link to heart valve damage. The damage was found to be a result of activity of fenfluramine and dexfenfluramine at the 5-HT2B serotonin receptor in heart valves. Newer combinations of SSRIs and phentermine, known as phenpro, have been used with equal efficiency as fenphen with no known heart valve damage due to lack of activity at this particular serotonin receptor due to SSRIs. There has been a recent resurgence in combination therapy clinical development with the development of 3 combinations: Qsymia (topiramate + phentermine), Empatic (bupropion + zonisamide) and Contrave (bupropion + naltrexone).
Other classes of drugs in development include lipase inhibitors, similar to orlistat. Another lipase inhibitor, called GT 389-255, was being developed by Peptimmune (licensed from Genzyme). This was a novel combination of an inhibitor and a polymer designed to bind the undigested triglycerides therefore allowing increased fat expulsion without side effects such as oily stools that occur with orlistat. The development stalled as Phase 1 trials were conducted in 2004 and there was no further human clinical development afterward. In 2011, Peptimmune filed for Chapter 7 Liquidation.
Another potential long-term approach to anti-obesity medication is through the development of ribonucleic acid interference (RNAi). Animal studies have illustrated that the deletion of the RIP140 gene in mice by genetic knockdown results in the lack of fat accumulation, even when mice are fed a high fat diet. Experiments conducted by Professor Malcolm Parker of Imperial College show that by silencing RIP 140, a nuclear hormone co-repressor which regulates fat accumulation, animal models exhibit a lean profile throughout their life, are resistant to diet-induced obesity, and show an enhanced metabolic rate. CytRx Corporation is developing RNAi therapeutics against this drug target for the treatment of obesity and type 2 diabetes. Similarly, another nuclear hormone receptor co-repressor, SMRT, has demonstrated an opposing effect in genetically engineered mice. Dr. Russell Nofsinger and Dr. Ronald Evans of the Salk Institute showed that disruption of the molecular interaction between SMRT and their nuclear hormone receptor partners leads to increased adiposity and a decreased metabolic rate. These studies suggest that new drugs targeting the molecular interaction between nuclear hormone receptors and their regulatory cofactors could provide a useful new category of therapeutic targets to be developed in an effort to control obesity.
Another approach is to induce a sense of satiety by occupying space in the gastric and intestinal cavities. One clinical trial involves a hydrogel (Gelesis) made of indigestible, food-grade materials. Another pilot study uses pseudobezoars.
- National Institute for Health and Clinical Excellence. Clinical guideline 43: Obesity: The prevention, identification, assessment and management of overweight and obesity in adults and children. London, 2006.
- "WIN – Publication – Prescription Medications for the Treatment of Obesity". National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). National Institutes of Health. Archived from the original on 13 January 2009. Retrieved 14 January 2009.
- "Anti-obesity drug no magic bullet". Canadian Broadcasting Corporation. 2 January 2007. Retrieved 19 September 2008.
- "FDA Briefing Document NDA 21-888 Zimulti (rimonabant) Tablets, 20 mg Sanofi Aventis Advisory Committee" (PDF). Food and Drug Administration. 13 June 2007. Archived from the original on 10 September 2008. Retrieved 19 September 2008.
- "Abbott Laboratories Voluntarily Withdraws Weight-loss Drug Sibutramine (Meridia) from the Canadian Market – Health Canada Information Update 2010-10-08".
- Snow V, Barry P, Fitterman N, Qaseem A, Weiss K (2005). "Pharmacologic and surgical management of obesity in primary care: a clinical practice guideline from the American College of Physicians". Ann. Intern. Med. 142 (7): 525–31. doi:10.7326/0003-4819-142-7-200504050-00011. PMID 15809464.
- Cooke D, Bloom S (2006). "The obesity pipeline: current strategies in the development of anti-obesity drugs". Nature reviews. Drug discovery 5 (11): 919–31. doi:10.1038/nrd2136. PMID 17080028.
- Bray, G. A. (1993). "Use and Abuse of Appetite-Suppressant Drugs in the Treatment of Obesity". Annals of Internal Medicine 119 (7, Pt. 2): 707–713. doi:10.7326/0003-4819-119-7_Part_2-199310011-00016.
- Parascandola J (November 1974). "Dinitrophenol and bioenergetics: an historical perspective". Mol. Cell. Biochem. 5 (1–2): 69–77. doi:10.1007/BF01874175. PMID 4610359.
- Pool, Robert (2001). Fat: Fighting the Obesity Epidemic. Oxford, UK: Oxford University Press. ISBN 0-19-511853-7.
- Weintraub M (May 1992). "Long-term weight control: The National Heart, Lung, and Blood Institute funded multimodal intervention study". Clin. Pharmacol. Ther. 51 (5): 581–5. PMID 1445528.
- Kolata,Gina (2007). Rethinking thin: The new science of weight loss – and the myths and realities of dieting. Picador. ISBN 0-312-42785-9.
- Aronne, L.J.; Powell, A.G. & Apovian C.M. (2011). "Emerging pharmacotherapy for obesity". Expert Opinion on Emerging Drugs 16 (3): 587–96. doi:10.1517/14728214.2011.609168. PMID 21834735.
- Obesity, Fitness & Wellness Week (14 August 2004). "Legal Issues; Court dismisses claims against anti-obesity medication". Retrieved 9 April 2012.
- Rockoff, Jonathan D.; Dooren, Jennifer Corbett (8 October 2010). "Abbott Pulls Diet Drug Meridia Off US Shelves". The Wall Street Journal. Archived from the original on 11 October 2010. Retrieved 8 October 2010.
- "Top obesity drug sibutramine being suspended". BBC News. 22 January 2010. Archived from the original on 25 January 2010. Retrieved 22 January 2010.
- (German) Sibutramin-Vertrieb in der Europäischen Union ausgesetzt . Abbott Laboratories in Germany. Press Release 2010-01-21. Retrieved 2010-01-27
- "Sibutramine (brand name Reductil) Information – Australia". Abbott Laboratories. 2010. Archived from the original on 14 October 2010. Retrieved 8 October 2010.
- Health Canada Endorsed Important Safety Information on MERIDIA (Sibutramine Hydrochloride Monohydrate): Subject: Voluntary withdrawal of Meridia (sibutramine) capsules from the Canadian market.
- "De-registration of pharmaceutical products containing sibutramine" (Press release). info.gov in Hong Kong. 2 November 2010. Retrieved 8 November 2010.
- "Top 10 Diet Pills That Work in 2014". TENMANIA. 2014. Retrieved April 15, 2014.
- Akbas F, Gasteyger C, Sjödin A, Astrup A, Larsen TM (January 2009). "A critical review of the cannabinoid receptor as a drug target for obesity management". Obes Rev 10 (1): 58–67. doi:10.1111/j.1467-789X.2008.00520.x. PMID 18721231.
- George A. Bray and Frank L. Greenway (1999). "Current and Potential Drugs for Treatment of Obesity: Table 19: Clinical trials with metformin for the treatment of obese diabetics". Endocrine Reviews 20 (6): 805–87. doi:10.1210/er.20.6.805. PMID 10605627. Retrieved 7 August 2006.
- de Luis DA, Gonzalez Sagrado M, Conde R, Aller R, Izaola O (2007). "Decreased basal levels of glucagon-like peptide-1 after weight loss in obese subjects". Ann. Nutr. Metab. 51 (2): 134–8. doi:10.1159/000103273. PMID 17536190.
- Abenhaim L; Moride Y; Brenot F et al. (August 1996). "Appetite-suppressant drugs and the risk of primary pulmonary hypertension. International Primary Pulmonary Hypertension Study Group". N. Engl. J. Med. 335 (9): 609–16. doi:10.1056/NEJM199608293350901. PMID 8692238.
- Alfred P. Fishman, MD (1999). "Aminorex to Fen/Phen: An Epidemic Foretold". Circulation 99 (1): 156–161. doi:10.1161/01.CIR.99.1.156. PMID 9884392. Retrieved 24 July 2006.
- U.S. Food and Drug Administration: The Facts About Weight Loss Products and Programs
- "Prepared Statement of the Federal Trade Commission on the Marketing of Dietary Supplements" (Press release). Committee on Governmental Affairs, United States Senate. 8 October 2002. Archived from the original on 25 August 2006. Retrieved 7 August 2006.
- Martin M, Schlabach G, Shibinski K (1998). "The Use of Nonprescription Weight Loss Products Among Female Basketball, Softball, and Volleyball Athletes from NCAA Division I Institutions: Issues and Concerns". J Athl Train 33 (1): 41–44. PMC 1320374. PMID 16558483.
- George A. Bray and Frank L. Greenway (1999). "Current and Potential Drugs for Treatment of Obesity: Postabsorptive modifiers of nutrient metabolism". Endocrine Reviews 20 (6): 805–87. doi:10.1210/er.20.6.805. PMID 10605627.
- Salynn Boyles (2012-07-17). "FDA approves diet drug Qsymia : agency warns of increased risk for oral birth defects". WebMD., citing "FDA approves weight-management drug Qsymia" (Press release). U.S. Food and Drug Administration. 2012-07-17.
- Lau DC, Douketis JD, Morrison KM, Hramiak IM, Sharma AM, Ur E (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.
- Onakpoya IJ, Posadzki PP, Watson LK, Davies LA, Ernst E (March 2012). "The efficacy of long-term conjugated linoleic acid (CLA) supplementation on body composition in overweight and obese individuals: a systematic review and meta-analysis of randomized clinical trials". Eur J Nutr (Systematic review) 51 (2): 127–34. doi:10.1007/s00394-011-0253-9. PMID 21990002.
- Shekelle PG, Hardy ML, Morton SC, et al. (March 2003). "Efficacy and safety of ephedra and ephedrine for weight loss and athletic performance: a meta-analysis". JAMA 289 (12): 1537–45. doi:10.1001/jama.289.12.1537. PMID 12672771.
- Bachorik, Lawrence. "FDA Announces Withdrawal Fenfluramine and Dexfenfluramine (Fen-Phen)". U.S. Food and Drug Administration. FDA. Retrieved 2014-01-27.
- , Launceston, Tasmania, Australia, Examiner, Friday, January 21, 1938, p 14, which states in postscript “However, the sex which for many years injured its health by tight lacing is not likely to be deterred from slimming by such considerations, The dictates of fashion will be paramount." Sir Arthur was particularly concerned with the neurological side effects of the then popular practice of dosing with thyroid extract to lose weight and, also, use of the then much vaunted weight loss drug dinitrophenol, which his report found killed as many patients as it reduced in girth, as well as, the compromise of the malnourished’s immune system and their consequent, often, inability to resist infectious diseases like the then endemic tuberculosis (archaic “epidemics of consumption”).
- See, also, , Sidney Morning Herald, Nov. 17, 1937, p 10.
- Johnson, Kimball. "Alli: A Weight Loss Drug". WebMD. WebMD. Retrieved 2014-01-27.
- "acarbose - oral, Precose". MedicineNet. MedicineNet. Retrieved 2014-01-27.
- Peptimmune homepage
- McBride, Ryan. "Genzyme-Spinout Peptimmune Files for Chapter 7 Liquidation". Xconomy Boston. Retrieved 5 September 2011.
- Leonardsson G; Steel JH; Christian M; Pocock V et al. (2004). "Nuclear receptor corepressor RIP140 regulates fat accumulation". Proc. Natl. Acad. Sci. U.S.A. 101 (22): 8437–42. doi:10.1073/pnas.0401013101. PMC 420412. PMID 15155905.
- Nofsinger RR, Li P, Hong SH, Jonker JW, Barish GD, Ying H, Cheng SY, Leblanc M, Xu W, Pei L, Kang YJ, Nelson M, Downes M, Yu RT, Olefsky JM, Lee CH, Evans RM. (2008). "SMRT repression of nuclear receptors controls the adipogenic set point and metabolic homeostasis". Proc. Natl. Acad. Sci. U.S.A. 105 (50): 20021–6. doi:10.1073/pnas.0811012105. PMC 2598729. PMID 19066220.
- "Research Shows First-of-Its-Kind Hydrogel Decreases Obese Patients’ Desire for Food", press release by the American Association of Clinical Endocrinologists, 22 April 2010 text
- Mintchev MP, Deneva MG, Aminkov BI, Fattouche M, Yadid-Pecht O, Bray RC (1 February 2010). "Pilot study of temporary controllable gastric pseudobezoars for dynamic non-invasive gastric volume reduction". Physiol. Meas. 31 (2): 131–44. doi:10.1088/0967-3334/31/2/001. PMID 20009188.