Anti-obesity medication

Orlistat (Xenical), the most commonly used medication to treat obesity and sibutramine (Meridia), a medication that was withdrawn due to cardiovascular side effects

Anti-obesity medication or weight loss medications are pharmacological agents that reduce or control excess body fat. These medications alter one of the fundamental processes of the human body, weight regulation, by: reducing appetite and consequently energy intake, increasing energy expenditure, redirecting nutrients from adipose to lean tissue, or interfering with the absorption of calories. ^{[1] [2] [3]}

Weight loss drugs have been developed since the early twentieth century, and many have been banned or withdrawn from the market due to adverse effects, including deaths; other drugs proved ineffective. Although many earlier drugs were stimulants such as amphetamines, in the early 2020s, GLP-1 receptor agonists became popular for weight loss.

The medications liraglutide, ^[4] naltrexone/bupropion, ^[5] orlistat, ^[6] semaglutide, ^[7] and tirzepatide ^[8] are approved by the US Food and Drug Administration (FDA) for weight management in combination with reduced-calorie diet and increased physical activity. As of 2022, no medication has been shown to be as effective at long-term weight reduction as bariatric surgery. ^[9] The main treatment modalities for obesity remain dieting (healthy diet and caloric restriction) and physical exercise.

Mechanisms of action

Energy intake

• 5-HT_2C receptor agonists reduce appetite by working on serotonin receptors in a region of the brain called the hypothalamus. ^[10] Lorcaserin (Belviq) was FDA approved for weight loss but was withdrawn from the market because a safety clinical trial shows an increased occurrence of cancer. ^[11]
• Cannabinoid receptor antagonists were developed to treat obesity because researchers noticed that cannabinoid agonists (such as THC, the main pharmacologically active component of cannabis), increased appetite. However, some drugs in this class such as rimonabant were withdrawn or ceased development to concerns about mental health and suicide. More selective drugs—some are in development that act only in peripheral tissues, not the brain—may be able to achieve this result with fewer adverse effects. ^{[12] [13]}
• GLP-1 agonists such as tirzepatide, semaglutide, and liraglutide slow gastric emptying and also have neurologically driven effects on appetite. ^[14] It is unknown if GLP-1 agonists or dual/triple agonists of GLP-1 and/or the glucagon or GIP receptors act solely by reducing energy intake or if they also increase energy expenditure. ^[15]
• Setmelanotide is an agonist of the melanocortin 4 receptor and is used in people with certain rare genetic conditions that cause obesity. It is less effective and not approved for general obesity. ^[16]
• Some weight loss drugs act on the neurotransmitters serotonin, dopamine, and norepinephrine to reduce appetite. ^[17]

Energy expenditure

• Adrenergic agonists that work on the beta-2 adrenergic receptor increase energy expenditure. Although some such as clenbuterol are used without medical approval for weight loss, none have achieved approval for this indication due to cardiac risks. ^{[18] [19]} The anti-obesity effects of amphetamines, besides acting on the brain to reduce energy intake, are also mediated by the beta-2 adrenergic receptor. ^{[20] [17]} Ephedrine (and related compounds that are also active ingredients in ephedra preparations) exert their effects by acting directly and indirectly as adrenergic agonists. ^[21]
• The discontinued drug 2,4-dinitrophenol works by increasing energy expenditure by decreasing the efficiency of mitochondria (uncoupling agent). ^[18] A prodrug of DNP, HU6, has been tested in clinical trials for weight loss and fatty liver disease. ^[22]
• Fibroblast growth factor-21 receptor agonists and drugs increasing FGF-21 activity are being investigated for obesity-related diseases; they can increase energy expenditure and several have been tested in humans. ^{[23] [24]}
• Thyroid hormones, another early weight loss drug, also raised energy expenditure but ceased to be used for weight loss due to cardiac risks and other adverse effects. ^[18] Selective thyromimetics that work on the thyroid hormone receptor beta may be able to exert some of the beneficial thermogenic effects of thyroid hormones with fewer adverse effects, but none have received approval as of 2023. ^[15]

Both

• Amylin analogues can both reduce energy intake and increase expenditure and can usefully be combined with leptin analogues for synergistic effect. ^{[25] [26]} The dual amylin and calcitonin receptor agonist cagrilintide, in combination with semaglutide, was more effective than semaglutide alone in promoting weight loss in clinical trials. ^{[27] [28]}
• Glucagon receptor agonists both reduce energy intake and increase energy expenditure in humans. They can cause hyperglycemia so it is recommended to combine them with a hypoglycemic drug, such as a GLP-1 or GIP receptor agonist. ^{[29] [30]}

Other mechanisms

• Bimagrumab, an experimental drug, works by inhibiting the action of myostatin, which limits the size of skeletal muscle. The drug has shown the ability to increase lean mass simultaneously to decreasing fat mass in obese humans, which is beneficial because it preserves or increases energy expenditure while reducing risks associated with excess fat. ^[18]
• Orlistat (Xenical) and cetilistat reduce intestinal fat absorption by inhibiting pancreatic lipase, an enzyme that breaks down triglycerides in the intestine. Without this enzyme, triglycerides from the diet are prevented from being hydrolyzed into absorbable free fatty acids and are excreted undigested. ^[31] Frequent oily bowel movements steatorrhea is a possible side effect of using Orlistat. Originally available only by prescription, it was approved by the FDA for over-the-counter sale in February 2007. ^[32] In May 2010, the U.S. Food and Drug Administration (FDA) approved a revised label for Xenical to include new safety information about rare cases of severe liver injury that have been reported with the use of this medication. ^[33] A 2010 phase 2 trial found cetilistat significantly reduced weight and was better tolerated than orlistat. ^[34]
• SGLT2 inhibitors cause the loss of 60–100 grams (2.1–3.5 oz) glucose in the urine each day and are associated with a modest, sustained weight loss of 1.5–2 kilograms (3.3–4.4 lb) in people with type 2 diabetes. The weight loss is less than expected due to compensatory increases in energy intake, but is additive when combined with GLP-1 receptor agonists. ^[35]

History

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. ^[36] 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. Overdose caused fatal hyperthermia and DNP also caused cataracts in some users. After the passage of the Food, Drug, and Cosmetic Act in 1938, the FDA banned DNP for human consumption. ^[37]

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 diet pill" regime. ^[38] 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. ^[38] 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. ^[39] While rainbow diet pills were banned in the US in the late 1960s, they reappeared in South America and Europe in the 1980s. ^[38] In 1959, phentermine had been FDA approved and fenfluramine in 1973. In the early 1990s two studies found that a combination of the drugs was more effective than either on its own; fen-phen became popular in the United States and had more than 18 million prescriptions in 1996. ^[40] Evidence mounted that the combination could cause valvular heart disease in up to 30 percent of those who had taken it, leading to withdrawal of fen-phen and dexfenfluramine from the market in September 1997. ^[39]

In the early 2020s, GLP-1 receptor agonists such as semaglutide or tirzepatide became popular for weight loss because they are more effective than earlier drugs, causing a shortage for patients prescribed these medications for type 2 diabetes, their original indication. ^{[41] [42]}

Patient population

The United States Food and Drug Administration and the European Medicines Agency have approved weight loss medications for adults with either a body-mass index (BMI) of at least 30, or a body-mass index of at least 27 with at least one weight-related comorbidity. This patient population is considered to have sufficiently high baseline health risks to justify the use of anti-obesity medication. ^{[43] [44]}

The American Academy of Pediatrics had not previously supported the use of weight loss medication in adolescents but issued new guidelines in 2023. It now recommends considering the use of weight loss medication in some overweight children aged 12 or older. ^[45] The European Medicines Agency has approved semaglutide for children aged 12 or older who have a BMI in the 95 percentile for their age and a weight of at least 60 kilograms (130 lb). ^{[46] [44]} However, GLP-1 agonists may not be cost effective in this population. ^[47]

Medication

US FDA approved

The US Food and Drug Administration (FDA) approves anti-obesity medications as an adjunctive therapy to diet and exercise for people for whom lifestyle changes do not result in sufficient weight loss. In the United States, semaglutide (Wegovy) is approved by the FDA for chronic weight management. ^[48] The FDA guidelines say that a therapy may be approved if it results in weight loss that is statistically significant greater than placebo and generally at least five percent of body weight over six months that comes predominantly from fat mass. ^{[18] [49]} Some other prescription weight loss medications are stimulants, which are recommended only for short-term use, and thus are of limited usefulness for patients who may need to reduce weight over months or years. ^[50] As of 2022, there is no pathway for approval for drugs that reduce fat mass without 5 percent overall weight loss, even if they significantly improve metabolic health; neither is there one for drugs that help patients maintain weight loss although this can be more challenging than losing weight. ^[18]

As of 2022, no medication has been discovered that would equal the effectiveness of bariatric surgery for long-term weight loss and improved health outcomes. ^[9]

Medication Name	Trade name(s)	Mechanism of action	Current FDA Status	placebo-adjusted percent bodyweight lost (highest dose studied)
Semaglutide	Wegovy	GLP-1 receptor agonist	Approved for weight management (chronic)	12% [51]
Phentermine/topiramate	Qsymia	Phentermine is a substituted amphetamine and topiramate has an unknown mechanism of action	Approved for weight management (short-term) by the FDA but not the European Medicines Agency [52]	10% [53] or 8.25 kilograms (18.2 lb) [54]
Naltrexone/bupropion	Contrave		Approved for weight management (chronic) in the US and EU [55]	5 percent [17]
Liraglutide	Saxenda	GLP-1 receptor agonist	Approved for weight management (chronic)	4 percent [56]
Gelesis100	Plenity	Oral hydrogel	FDA approved for weight management (chronic) but the American Gastroenterology Association recommends that its use be limited to clinical trials due to lack of evidence. [57]	2% [58]
Orlistat	Xenical	Absorption inhibitor	Approved for weight management (chronic)	3 kilograms (6.6 lb); percentage not provided [59]
Phentermine		Substituted amphetamine	Approved for weight management (short-term)	5 kilograms (11 lb) [60]
Methamphetamine	Desoxyn	Substituted amphetamine	Approved for weight management (short-term)
Tirzepatide	Zepbound	Dual GLP-1 receptor agonist and GIP agonist	FDA approved for weight management (chronic); [61] EMA approval for weight loss is pending [62]	10.91 kilograms (24.1 lb) [63]

Withdrawn

Medication Name	Trade name(s)	Mechanism of action	Current FDA Status	placebo-adjusted percent bodyweight lost (highest dose studied)
Lorcaserin	Belviq	5-HT2C receptor agonist	Withdrawn for safety reasons	6.25 percent [64]
Sibutramine	Meridia	Serotonin–norepinephrine reuptake inhibitor	Withdrawn due to cardiovascular risks [65] [66]	19.7 percent [67]
Rimonabant	Acomplia, Zimbutli	Cannabinoid receptor antagonist	Withdrawn for safety reasons	2.6 to 6.3 kilograms (5.7 to 13.9 lb) [68]
Fenfluramine		Serotonin releasing agent	Withdrawn for safety reasons	-
Fenfluramine/phentermine (fen-phen)	Pondimin		Withdrawn for safety reasons	13.9 percent [69]
Dexfenfluramine	Redux	Serotonin releasing agent	Withdrawn for safety reasons	3.5 kilograms (7.7 lb) [70]
2,4-Dinitrophenol		Uncoupling agent	Withdrawn for safety reasons	17.1 pounds (7.8 kg) per patient on average (uncontrolled study) [71]
Ephedrine		Adrenergic agonist	Approved for asthma [72]	Average of 1.9 kilograms (4.2 lb) in a meta-analysis (all dosages) [73]
ECA stack		Combination of ephedrine and caffeine, sometimes adding aspirin		Around 4–6 kilograms (8.8–13.2 lb) [74]
Ephedra	Plant extract sold as a dietary supplement	Contains ephedrine, an adrenergic agonist	Banned in 2004 for safety reasons	0.9 kilograms (2.0 lb) per month more than placebo [74]
Amphetamine salts	Obetrol		Approved 1960, withdrawn 1973; Adderall was later approved for ADHD and narcolepsy and is still used for those purposes
Phenylpropanolamine	Was an over-the-counter medication ingredient		Withdrawn in 2005 due to risk of hemorragic stroke	1.5 kilograms (3.3 lb) [75]

Never approved

Medication Name	Trade name(s)	Mechanism of action	Current FDA Status	placebo-adjusted percent bodyweight lost (highest dose studied)
Retatrutide		GLP-1, GIP, and glucagon receptor triple agonist	In clinical trials	24 percent in a Phase II trial [76]
Exenatide	Byetta	GLP-1 receptor agonist	Approved for type 2 diabetes	2.5 kilograms (5.5 lb) [77]
Cetilistat		Absorption inhibitor	Not approved	1.5 kilograms (3.3 lb) [78]
Tesofensine (NS2330)		Serotonin–norepinephrine–dopamine reuptake inhibitor	Not FDA approved	10.6 percent [79]
Metformin	Glucophage	Unknown	Approved for type 2 diabetes	5.6 percent [80]
Cagrilintide		Dual amylin and calcitonin receptor agonist (DACRA)	Not approved	7.8 percent [81]
Cagrilintide/semaglutide	CagriSema	DACRA/GLP-1 agonist combination	Not approved	15.4 percent after 32 weeks [27]

Safety and side effects

Some anti-obesity medications 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. ^[82] Out of 25 anti-obesity medications withdrawn from the market between 1964 and 2009, 23 acted by altering the functions of chemical neurotransmitters in the brain. The most common side effects of these drugs that led to withdrawals were mental disturbances, cardiac side effects, and drug abuse or drug dependence. Deaths were associated with seven products. ^[83] Ephedra was removed from the US market in 2004 over concerns that it raises blood pressure and could lead to strokes and death. ^[84]

References

1. Ryan DH (September 2021). "Next Generation Antiobesity Medications: Setmelanotide, Semaglutide, Tirzepatide and Bimagrumab: What do They Mean for Clinical Practice?". Journal of Obesity & Metabolic Syndrome. 30 (3): 196–208. doi:10.7570/jomes21033. ISSN   2508-6235. PMC   8526285 . PMID   34518444.
2. Jimenez-Munoz CM, López M, Albericio F, Makowski K (May 2021). "Targeting Energy Expenditure—Drugs for Obesity Treatment". Pharmaceuticals. 14 (5): 435. doi: 10.3390/ph14050435 . ISSN   1424-8247. PMC   8148206 . PMID   34066399.
3. 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.
4. "Saxenda- liraglutide injection, solution". DailyMed.
5. "Contrave extended release- naltrexone hydrochloride and bupropion hydrochloride tablet, extended release". DailyMed.
6. "Xenical- orlistat capsule". DailyMed.
7. "Wegovy- semaglutide injection, solution". DailyMed.
8. "Zepbound- tirzepatide injection, solution". DailyMed.
9. Müller TD, Blüher M, Tschöp MH, DiMarchi RD (March 2022). "Anti-obesity drug discovery: advances and challenges". Nature Reviews Drug Discovery. 21 (3): 201–223. doi:10.1038/s41573-021-00337-8. PMC   8609996 . PMID   34815532.
10. Shukla AP, Kumar RB, Aronne LJ (2015). "Lorcaserin Hcl for the treatment of obesity". Expert Opinion on Pharmacotherapy. 16 (16): 2531–2538. doi:10.1517/14656566.2015.1096345. PMID   26472579. S2CID   44520532.
11. "FDA requests the withdrawal of the weight-loss drug Belviq, Belviq XR (lorcaserin) from the market". U.S. Food and Drug Administration (FDA). 19 February 2019. Archived from the original on 20 December 2020. Retrieved 23 December 2020.
12. Rohbeck E, Eckel J, Romacho T (March 2021). "Cannabinoid Receptors in Metabolic Regulation and Diabetes". Physiology. 36 (2): 102–113. doi:10.1152/physiol.00029.2020. PMID   33595385. S2CID   231943477.
13. Nguyen T, Thomas BF, Zhang Y (2019). "Overcoming the psychiatric side effects of the cannabinoid CB1 receptor antagonists: current approaches for therapeutics development". Current Topics in Medicinal Chemistry. 19 (16): 1418–1435. doi:10.2174/1568026619666190708164841. ISSN   1568-0266. PMC   6771026 . PMID   31284863.
14. Shah M, Vella A (September 2014). "Effects of GLP-1 on appetite and weight". Reviews in Endocrine & Metabolic Disorders. 15 (3): 181–187. doi:10.1007/s11154-014-9289-5. PMC   4119845 . PMID   24811133.
15. Genchi VA, Palma G, Sorice GP, D'Oria R, Caccioppoli C, Marrano N, et al. (November 2023). "Pharmacological modulation of adaptive thermogenesis: new clues for obesity management?". Journal of Endocrinological Investigation. 46 (11): 2213–2236. doi:10.1007/s40618-023-02125-0. ISSN   1720-8386. PMC   10558388 . PMID   37378828.
16. Son JW, Kim S (December 2020). "Comprehensive Review of Current and Upcoming Anti-Obesity Drugs". Diabetes & Metabolism Journal. 44 (6): 802–818. doi: 10.4093/dmj.2020.0258 . PMC   7801751 . PMID   33389955.
17. Coulter AA, Rebello CJ, Greenway FL (July 2018). "Centrally Acting Drugs for Obesity: Past, Present, andFuture". Drugs. 78 (11): 1113–1132. doi:10.1007/s40265-018-0946-y. ISSN   0012-6667. PMC   6095132 . PMID   30014268.
18. Christoffersen BØ, Sanchez-Delgado G, John LM, Ryan DH, Raun K, Ravussin E (April 2022). "Beyond appetite regulation: Targeting energy expenditure, fat oxidation, and lean mass preservation for sustainable weight loss". Obesity. 30 (4): 841–857. doi:10.1002/oby.23374. ISSN   1930-7381. PMC   9310705 . PMID   35333444.
19. Kumari S, Pal B, Sahu SK, Prabhakar PK, Tewari D (July 2023). "Adverse events of clenbuterol among athletes: a systematic review of case reports and case series". International Journal of Legal Medicine. 137 (4): 1023–1037. doi:10.1007/s00414-023-02996-1. PMID   37062796. S2CID   258178293.
20. Morris A (July 2020). "Unravelling novel weight loss mechanisms". Nature Reviews Endocrinology. 16 (7): 343. doi: 10.1038/s41574-020-0374-4 . ISSN   1759-5037. PMID   32461617. S2CID   218913041.
21. Munafò A, Frara S, Perico N, Di Mauro R, Cortinovis M, Burgaletto C, et al. (December 2021). "In search of an ideal drug for safer treatment of obesity: The false promise of pseudoephedrine". Reviews in Endocrine and Metabolic Disorders. 22 (4): 1013–1025. doi:10.1007/s11154-021-09658-w. ISSN   1573-2606. PMC   8724077 . PMID   33945051.
22. Harrison SA, Loomba R, Dubourg J, Ratziu V, Noureddin M (July 2023). "Clinical Trial Landscape in NASH". Clinical Gastroenterology and Hepatology. 21 (8): 2001–2014. doi:10.1016/j.cgh.2023.03.041. PMID   37059159. S2CID   258115543.
23. Sonoda J, Chen MZ, Baruch A (May 2017). "FGF21-receptor agonists: an emerging therapeutic class for obesity-related diseases". Hormone Molecular Biology and Clinical Investigation. 30 (2). doi: 10.1515/hmbci-2017-0002 . ISSN   1868-1891. PMID   28525362. S2CID   4420935.
24. Abdi Beshir S, Ahmed Elnour A, Soorya A, Parveen Mohamed A, Sir Loon Goh S, Hussain N, et al. (October 2023). "A narrative review of approved and emerging anti-obesity medications". Saudi Pharmaceutical Journal. 31 (10): 101757. doi:10.1016/j.jsps.2023.101757. ISSN   1319-0164. PMC   10497995 . PMID   37712012.
25. Lutz TA (December 2016). "Gut hormones such as amylin and GLP-1 in the control of eating and energy expenditure". International Journal of Obesity Supplements. 6 (1): S15–S21. doi:10.1038/ijosup.2016.4. ISSN   2046-2174. PMC   5485879 . PMID   28685025.
26. Mietlicki-Baase EG (August 2016). "Amylin-mediated control of glycemia, energy balance, and cognition". Physiology & Behavior. 162: 130–140. doi:10.1016/j.physbeh.2016.02.034. ISSN   0031-9384. PMC   4899204 . PMID   26922873.
27. Idris I (July 2023). "Coadministration of the long-acting amylin analog cagrilintide plus semaglutide ( CagriSema ), resulted in significantly greater weight loss, along with improved measures of glucose control, in a short phase 2 trial of patients with type 2 diabetes". Diabetes, Obesity and Metabolism Now. 1 (7). doi: 10.1002/doi2.68 . ISSN   2688-8939. S2CID   260221980.
28. Holst JJ, Jepsen SL, Modvig I (April 2022). "GLP-1 – Incretin and pleiotropic hormone with pharmacotherapy potential. Increasing secretion of endogenous GLP-1 for diabetes and obesity therapy". Current Opinion in Pharmacology. 63: 102189. doi: 10.1016/j.coph.2022.102189 . PMID   35231672. S2CID   247153792.
29. Conceição-Furber E, Coskun T, Sloop KW, Samms RJ (April 2022). "Is Glucagon Receptor Activation the Thermogenic Solution for Treating Obesity?". Frontiers in Endocrinology. 13: 868037. doi: 10.3389/fendo.2022.868037 . ISSN   1664-2392. PMC   9081793 . PMID   35547006.
30. Novikoff A, Müller TD (July 2023). "The molecular pharmacology of glucagon agonists in diabetes and obesity". Peptides. 165: 171003. doi:10.1016/j.peptides.2023.171003. ISSN   0196-9781. PMC   10265134 . PMID   36997003.
31. Yamada Y, Kato T, Ogino H, Ashina S, Kato K (August 2008). "Cetilistat (ATL-962), a novel pancreatic lipase inhibitor, ameliorates body weight gain and improves lipid profiles in rats". Hormone and Metabolic Research. 40 (8): 539–543. doi:10.1055/s-2008-1076699. PMID   18500680. S2CID   29076657.
32. "Orlistat (marketed as Alli and Xenical) Information". U.S. Food and Drug Administration. 8 July 2015. Retrieved 14 January 2024.
33. "FDA Drug Safety Communication: Completed safety review of Xenical/Alli (orlistat) and severe liver injury". U.S. Food and Drug Administration (FDA). Archived from the original on 24 April 2019. Retrieved 16 December 2019.
34. Kopelman P, Groot G, Rissanen A, Rossner S, Toubro S, Palmer R, et al. (January 2010). "Weight loss, HbA1c reduction, and tolerability of cetilistat in a randomized, placebo-controlled phase 2 trial in obese diabetics: comparison with orlistat (Xenical)". Obesity. 18 (1): 108–115. doi: 10.1038/oby.2009.155 . PMID   19461584. S2CID   205526626.
35. Pereira MJ, Eriksson JW (2019). "Emerging Role of SGLT-2 Inhibitors for the Treatment of Obesity". Drugs. 79 (3): 219–230. doi: 10.1007/s40265-019-1057-0 . ISSN   0012-6667. PMC   6394798 . PMID   30701480.
36. Parascandola J (November 1974). "Dinitrophenol and bioenergetics: an historical perspective". Molecular and Cellular Biochemistry. 5 (1–2): 69–77. doi:10.1007/BF01874175. PMID   4610359. S2CID   2656970.
37. Swann JP (2010). "Reducing with dinitrophenol : self-medication, and the challenge of regulating a dangerous pharmaceutical before the US Food, Drug, and Cosmetic Act". Perspectives on Twentieth-century Pharmaceuticals. Peter Lang. pp. 289, 292, 299, 301. ISBN   978-3-03910-920-3.
38. Cohen PA, Goday A, Swann JP (September 2012). "The return of rainbow diet pills". American Journal of Public Health. 102 (9): 1676–1686. doi:10.2105/AJPH.2012.300655. PMC   3482033 . PMID   22813089.
39. Pool R (2001). Fat: Fighting the Obesity Epidemic . Oxford, UK: Oxford University Press. ISBN   978-0-19-511853-7.
40. Setola V, Roth BL (October 2005). "Screening the receptorome reveals molecular targets responsible for drug-induced side effects: focus on 'fen–phen'". Expert Opinion on Drug Metabolism & Toxicology. 1 (3): 377–387. doi:10.1517/17425255.1.3.377. PMID   16863450. S2CID   30930020.
41. Lafferty RA, Flatt PR, Irwin N (March 2023). "GLP-1/GIP analogs: potential impact in the landscape of obesity pharmacotherapy". Expert Opinion on Pharmacotherapy. 24 (5): 587–597. doi: 10.1080/14656566.2023.2192865 . PMID   36927378. S2CID   257580812.
42. "GLP-1 receptor agonists: Breaking down the hype and demand". American Pharmacists Association. Archived from the original on 1 November 2023. Retrieved 1 November 2023.
43. Colman E (February 2007). "Guidance for Industry Developing Products for Weight Management". Food and Drug Administration . Archived from the original on 13 October 2022. Retrieved 19 July 2022.
44. "Wegovy". European Medicines Agency. 11 November 2021. Archived from the original on 2 July 2022. Retrieved 3 November 2023.
45. "A major medical group updated its guidance for treating childhood obesity. Here's what it says". NBC News. 9 January 2023. Archived from the original on 1 November 2023. Retrieved 1 November 2023.
46. "European Medicines Agency recommends weight loss drug Wegovy for teenagers 12 and up". Diabetes. Archived from the original on 1 November 2023. Retrieved 1 November 2023.
47. "Latest Obesity Drug Not Cost-Effective for Adolescents". Columbia University Irving Medical Center. 12 September 2023. Archived from the original on 1 November 2023. Retrieved 1 November 2023.
48. "FDA Approves New Drug Treatment for Chronic Weight Management, First Since 2014". U.S. Food and Drug Administration (FDA) (Press release). 21 June 2021. Archived from the original on 4 June 2021. Retrieved 19 July 2022.
49. Haslam D (March 2016). "Weight management in obesity – past and present". International Journal of Clinical Practice. 70 (3): 206–217. doi:10.1111/ijcp.12771. ISSN   1368-5031. PMC   4832440 . PMID   26811245.
50. "Obesity Medication: Gastrointestinal Agents, Other, CNS Stimulants, Anorexiants, Glucagon-like Peptide-1 Agonists, Antidepressants, dopamine reuptake inhibitors; opioid antagonists". emedicine.medscape.com. Archived from the original on 4 November 2016. Retrieved 2 November 2016.
51. Wilding JP, Batterham RL, Calanna S, Davies M, Van Gaal LF, Lingvay I, et al. (March 2021). "Once-Weekly Semaglutide in Adults with Overweight or Obesity". The New England Journal of Medicine. 384 (11): 989–1002. doi: 10.1056/NEJMoa2032183 . PMID   33567185. S2CID   231883214. Archived from the original on 18 March 2023. Retrieved 21 February 2023.
52. "Qsiva". European Medicines Agency (EMA). 13 June 2013. Archived from the original on 12 December 2022. Retrieved 12 December 2022.
53. Smith SM, Meyer M, Trinkley KE (March 2013). "Phentermine/topiramate for the treatment of obesity". The Annals of Pharmacotherapy. 47 (3): 340–349. doi:10.1345/aph.1R501. PMID   23482732. S2CID   30461611.
54. Lei X, Ruan J, Lai C, Sun Z, Yang X (June 2021). "Efficacy and Safety of Phentermine/Topiramate in Adults with Overweight or Obesity: A Systematic Review and Meta-Analysis". Obesity. 29 (6): 985–994. doi:10.1002/oby.23152. PMID   33864346. S2CID   233278420.
55. "Mysimba EPAR". European Medicines Agency (EMA). 17 September 2018. Archived from the original on 22 October 2020. Retrieved 5 August 2020.
56. Alruwaili H, Dehestani B, le Roux CW (March 2021). "Clinical Impact of Liraglutide as a Treatment of Obesity". Clinical Pharmacology: Advances and Applications. 13: 53–60. doi: 10.2147/CPAA.S276085 . ISSN   1179-1438. PMC   7958997 . PMID   33732030.
57. Grunvald E, Shah R, Hernaez R, Chandar AK, Pickett-Blakely O, Teigen LM, et al. (November 2022). "AGA Clinical Practice Guideline on Pharmacological Interventions for Adults With Obesity". Gastroenterology. 163 (5): 1198–1225. doi: 10.1053/j.gastro.2022.08.045 . PMID   36273831. S2CID   253052479.
58. Greenway FL, Aronne LJ, Raben A, Astrup A, Apovian CM, Hill JO, et al. (February 2019). "A Randomized, Double-Blind, Placebo-Controlled Study of Gelesis100: A Novel Nonsystemic Oral Hydrogel for Weight Loss". Obesity. 27 (2): 205–216. doi:10.1002/oby.22347. PMC   6587502 . PMID   30421844.
59. Padwal RS, Majumdar SR (January 2007). "Drug treatments for obesity: orlistat, sibutramine, and rimonabant". Lancet. 369 (9555): 71–77. doi:10.1016/S0140-6736(07)60033-6. PMID   17208644. S2CID   35104831.
60. Kim KK, Cho H, Kang H, Youn B, Lee K (October 2006). "Effects on Weight Reduction and Safety of Short-Term Phentermine Administration in Korean Obese People". Yonsei Medical Journal. 47 (5): 614–625. doi:10.3349/ymj.2006.47.5.614. ISSN   0513-5796. PMC   2687747 . PMID   17066505.
61. "FDA Approves Lilly's Zepbound™ (tirzepatide) for Chronic Weight Management, a Powerful New Option for the Treatment of Obesity or Overweight with Weight-Related Medical Problems". investor.lilly.com/. 8 November 2023. Archived from the original on 13 November 2023. Retrieved 13 November 2023.
62. "EU regulator recommends Eli Lilly's Mounjaro for weight management". Reuters. 10 November 2023. Archived from the original on 16 November 2023. Retrieved 16 November 2023.
63. Lin F, Yu B, Ling B, Lv G, Shang H, Zhao X, et al. (4 May 2023). "Weight loss efficiency and safety of tirzepatide: A Systematic review". PLOS ONE. 18 (5): e0285197. Bibcode:2023PLoSO..1885197L. doi: 10.1371/journal.pone.0285197 . ISSN   1932-6203. PMC   10159347 . PMID   37141329. Over all, meta-analysis showed a significant reduction in body weight in the tirzepatide group versus the placebo group by -9.81 kg (95% CI (-12.09, -7.52). There were three doses investigated compared to the placebo group were affected significantly reduced the body weight of patients [5 mg: MD = -7.52 kg, 95% CI (-10.86, -4.18), P < 0.0001; I2 = 94%; 10 mg: MD = -10.48 kg, 95% CI (-15.34, -5.62), P < 0.0001; I2 = 97%; 15 mg: MD = -10.91 kg, 95% CI (-14.81, -7.01), P < 0.00001; I2 = 96%]
64. Tuccinardi D, Farr OM, Upadhyay J, Oussaada SM, Mathew H, Paschou SA, et al. (June 2019). "Lorcaserin treatment decreases body weight and improves cardiometabolic risk factors of obese adults: A 6-month-long, randomized, placebo-controlled, double-blind clinical trial". Diabetes, Obesity & Metabolism. 21 (6): 1487–1492. doi:10.1111/dom.13655. ISSN   1462-8902. PMC   6504613 . PMID   30724455.
65. "Meridia (sibutramine): Market Withdrawal Due to Risk of Serious Cardiovascular Events". Food and Drug Administration . Archived from the original on 18 January 2017. Retrieved 16 December 2019.
66. "Recalls and safety alerts". Health Canada. Government of Canada. 23 October 2012. Archived from the original on 23 October 2020. Retrieved 31 August 2020.
67. Dedov II, Melnichenko GA, Troshina EA, Mazurina NV, Galieva MO (September 2018). "Body Weight Reduction Associated with the Sibutramine Treatment: Overall Results of the PRIMAVERA Primary Health Care Trial". Obesity Facts. 11 (4): 335–343. doi:10.1159/000488880. ISSN   1662-4025. PMC   6189539 . PMID   30089303.
68. Christopoulou FD, Kiortsis DN (February 2011). "An overview of the metabolic effects of rimonabant in randomized controlled trials: potential for other cannabinoid 1 receptor blockers in obesity: The metabolic effects of rimonabant". Journal of Clinical Pharmacy and Therapeutics. 36 (1): 10–18. doi: 10.1111/j.1365-2710.2010.01164.x . PMID   21198716. S2CID   3274949.
69. Wadden TA, Berkowitz RI, Silvestry F, Vogt RA, St John Sutton MG, Stunkard AJ, et al. (July 1998). "The fen-phen finale: a study of weight loss and valvular heart disease". Obesity Research. 6 (4): 278–284. doi: 10.1002/j.1550-8528.1998.tb00350.x . ISSN   1071-7323. PMID   9688104.
70. Davis R, Faulds D (November 1996). "Dexfenfluramine". Drugs. 52 (5): 696–724. doi:10.2165/00003495-199652050-00007. PMID   9118819. S2CID   195698330.
71. Tainter ML (August 1935). "Dinitrophenol in the Treatment of Obesity: Final Report". Journal of the American Medical Association. 105 (5): 332. doi:10.1001/jama.1935.02760310006002.
72. "Role of OTC Asthma Medications in the Community Pharmacy". Pharmacy Times. 8 December 2021. Archived from the original on 19 February 2023. Retrieved 24 October 2023.
73. Yoo H, Yoon H, Yee J, Gwak H (November 2021). "Effects of Ephedrine-Containing Products on Weight Loss and Lipid Profiles: A Systematic Review and Meta-Analysis of Randomized Controlled Trials". Pharmaceuticals. 14 (11): 1198. doi: 10.3390/ph14111198 . ISSN   1424-8247. PMC   8618781 . PMID   34832979.
74. Eckerson JM (2015). "Weight Loss Nutritional Supplements". Nutritional Supplements in Sports and Exercise. Springer International Publishing. pp. 159–185. doi:10.1007/978-3-319-18230-8_8. ISBN   978-3-319-18230-8. Archived from the original on 2 November 2023. Retrieved 24 October 2023.
75. Schteingart DE (July 1992). "Effectiveness of phenylpropanolamine in the management of moderate obesity". International Journal of Obesity and Related Metabolic Disorders: Journal of the International Association for the Study of Obesity. 16 (7): 487–493. PMID   1323545.
76. Jastreboff AM, Kaplan LM, Frías JP, Wu Q, Du Y, Gurbuz S, et al. (June 2023). "Triple-Hormone-Receptor Agonist Retatrutide for Obesity - A Phase 2 Trial". The New England Journal of Medicine. 389 (6): 514–526. doi:10.1056/NEJMoa2301972. PMID   37366315. S2CID   259260926. Free access subject to registration.
77. Dushay J, Gao C, Gopalakrishnan GS, Crawley M, Mitten EK, Wilker E, et al. (January 2012). "Short-Term Exenatide Treatment Leads to Significant Weight Loss in a Subset of Obese Women Without Diabetes". Diabetes Care. 35 (1): 4–11. doi:10.2337/dc11-0931. ISSN   0149-5992. PMC   3241299 . PMID   22040840.
78. Kopelman P, Groot Gd, Rissanen A, Rossner S, Toubro S, Palmer R, et al. (January 2010). "Weight loss, HbA1c reduction, and tolerability of cetilistat in a randomized, placebo-controlled phase 2 trial in obese diabetics: comparison with orlistat (Xenical)". Obesity (Silver Spring). 18 (1): 108–115. doi:10.1038/oby.2009.155. PMID   19461584. S2CID   205526626.
79. Axel AM, Mikkelsen JD, Hansen HH (June 2010). "Tesofensine, a Novel Triple Monoamine Reuptake Inhibitor, Induces Appetite Suppression by Indirect Stimulation of α1 Adrenoceptor and Dopamine D1 Receptor Pathways in the Diet-Induced Obese Rat". Neuropsychopharmacology. 35 (7): 1464–1476. doi:10.1038/npp.2010.16. ISSN   0893-133X. PMC   3055463 . PMID   20200509.
80. Seifarth C, Schehler B, Schneider HJ (January 2013). "Effectiveness of metformin on weight loss in non-diabetic individuals with obesity". Experimental and Clinical Endocrinology & Diabetes. 121 (1): 27–31. doi: 10.1055/s-0032-1327734 . ISSN   1439-3646. PMID   23147210. S2CID   20506527.
81. Lau DC, Erichsen L, Francisco AM, Satylganova A, le Roux CW, McGowan B, et al. (December 2021). "Once-weekly cagrilintide for weight management in people with overweight and obesity: a multicentre, randomised, double-blind, placebo-controlled and active-controlled, dose-finding phase 2 trial". The Lancet. 398 (10317): 2160–2172. doi:10.1016/S0140-6736(21)01751-7. PMID   34798060. S2CID   244169045.
82. Bachorik L. "FDA Announces Withdrawal Fenfluramine and Dexfenfluramine (Fen-Phen)". U.S. Food and Drug Administration. U.S. Food and Drug Administration (FDA). Archived from the original on 4 November 2009. Retrieved 27 January 2014.
83. Onakpoya IJ, Heneghan CJ, Aronson JK (2016). "Post-marketing withdrawal of anti-obesity medicinal products because of adverse drug reactions: a systematic review". BMC Medicine. 14 (1): 191. doi: 10.1186/s12916-016-0735-y . ISSN   1741-7015. PMC   5126837 . PMID   27894343.
84. Kolata G (2007). Rethinking thin: The new science of weight loss – and the myths and realities of dieting. Picador. ISBN   978-0-312-42785-6.

External links

• Media related to Anti-obesity medication at Wikimedia Commons
• Prescription Medications to Treat Overweight & Obesity US National Institute of Diabetes and Digestive and Kidney Diseases