anti-obesity medication anti-obesity medication anti-obesity medication or weight loss medications are pharmacological agents that reduce or control weight. these medications 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 individuals with obesity remain dieting (healthy diet and caloric restriction) and physical exercise. part of a series onhuman body weight general concepts obesity (epidemiology) overweight underweight body shape weight gain weight loss gestational weight gain diet (nutrition) weight management overnutrition childhood obesity (epidemiology) medical concepts adipose tissue classification of obesity genetics of obesity metabolic syndrome (epidemiology of metabolic syndrome) metabolically healthy obesity obesity paradox set point theory measurements body adiposity index body mass index body fat percentage body shape index corpulence index lean body mass relative fat mass waist–hip ratio waist-to-height ratio related conditions diabetes (type 1) eating disorder (anorexia • bulimia • binge eating disorder) food addiction hyperthyroidism malnutrition red-s starvation (starvation response) pcos obesity-associated morbidity arteriosclerosis atherosclerosis fatty liver disease gerd gynecomastia heart disease hypertension obesity and cancer osteoarthritis prediabetes sleep apnea type 2 diabetes management of obesity anti-obesity medication bariatrics bariatric surgery dieting (list of diets) caloric deficit exercise (outline) liposuction obesity medicine weight loss camp weight loss coaching yo-yo effect social aspects comfort food fast food (criticism) fat acceptance movement fat fetishism health at every size hunger obesity and the environment obesity and sexuality sedentary lifestyle social determinants of obesity social stigma of obesity weight cutting weight class orlistat (xenical), the most commonly used medication to treat obesity and sibutramine (meridia), a medication that was withdrawn due to cardiovascular side effects in the united states, orlistat (xenical) and semaglutide (wegovy) are approved by the fda for long-term use. because of potential side effects, and limited evidence of small benefits in weight reduction for children and adolescents with obesity, it is recommended that anti-obesity medications only be prescribed for obesity where it is hoped that the benefits of the treatment outweigh its risks. in the united states, the food and drug administration advocates that people with either a body-mass index of at least 30, or a body-mass index of at least 27 with at least one weight-related comorbidity, represent a patient population with sufficiently high baseline health risks to justify the use of anti-obesity medication. mechanisms of action anti-obesity medications may operate through one or more of the following mechanisms: catecholamine releasing agents such as amphetamine, phentermine, and related substituted amphetamines (e.g., bupropion) which act as appetite suppressants are the main tools used for the treatment of obesity. glp-1 analogues such as tirzepatide, semaglutide, and liraglutide slow gastric emptying and also have neurologically-driven effects on appetite. 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. 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, led 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 diet 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. while rainbow diet pills were banned in the us in the late 1960s, they reappeared in south america and europe in the 1980s. eventually rainbow diet pills were re-introduced into the us by the 2000s and led to additional adverse health effects. in 1959, phentermine had been fda approved and fenfluramine in 1973. the two were no more popular than other medications 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 fewer 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. medical complications included fatal pulmonary hypertension and heart valve damage due to redux and fen-phen, and hemorrhagic stroke due to phenylpropanolamine. since the introduction of medicines for the management of obesity in the 1930s, many compounds have been tried. most of them reduce body weight by small amounts, and several of them are no longer marketed for obesity because of their side effects. 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 reportedly associated with seven products. ephedra was removed from the us market in 2004 over concerns that it raises blood pressure and could lead to strokes and death. medication some patients find that diet and exercise is not a viable option; for these patients, anti-obesity medications can be a last resort. in the united states, semaglutide (wegovy) is approved by the fda for chronic weight management. 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. medication name trade name(s) current fda status placebo-adjusted percent bodyweight lost (highest dose studied) semaglutide wegovy approved for weight management (chronic) 12% phentermine/topirimate qsymia approved for weight management (short-term) 10% naltrexone/bupropion contrave approved for weight management (chronic) 5% liraglutide saxenda approved for weight management (chronic) 7 kg (percentage bodyweight not provided) gelesis100 plenity approved for weight management (chronic) 2% orlistat xenical approved for weight management (chronic) 3 kg; percentage not provided phentermine approved for weight management (short-term) exenatide byetta approved for type 2 diabetes cetilistat not approved - lorcaserin belviq withdrawn for safety reasons - sibutramine meridia withdrawn for safety reasons - rimonabant acomplia, zimbutli withdrawn for safety reasons - fenfluoramine withdrawn for safety reasons - fenfluramine/phentermine (fen-phen) pondimin withdrawn for safety reasons dexfenfluramine redux withdrawn for safety reasons metformin glucophage approved for type 2 diabetes amylin/pramlinatide approved for type 2 diabetes tirzepatide mounjaro approved for type 2 diabetes 18% thyroid hormones approved for people with hypothyroidism, not for weight loss in people with normal thyroid function 2,4-dinitrophenol never approved, for safety reasons amphetamine salts obetrol approved 1960, withdrawn 1973; adderall approved for adhd and narcolepsy digoxin (a digitalis leaf extract) lanoxin approved for certain cardiac indications and termination of fetal heartbeat; appetite reduction is a side effect phenylpropanolamine was an over-the-counter medication ingredient withdrawn in 2005 due to risk of hemorragic stroke ephedra plant extract sold as a dietary supplement banned in 2004 for safety reasons glp-1 analogs and agonists glucagon-like peptide-1 (glp-1) are peptide incretin hormones involved in blood sugar control. in 2021, one review concluded that "currently, gut peptide analogues such as semaglutide and tirzepatide are the furthest advanced in clinical development". in 2022, a further review found that these two peptides are "the most promising candidates for the upcoming battle in the anti-obesity market". an article in the new york times notes the high costs for semaglutide and potentially tirzepatide, suggesting that many people "who could most benefit from weight loss may be unable to afford such expensive drugs". semaglutide semaglutide (ozempic) is a glp-1 analogue, administered once weekly. it is more effective than exenatide. in june 2021, the us food and drug administration (fda) approved semaglutide injection sold under the brand name wegovy for long-term weight management in adults. wegovy was approved for medical use ("used together with diet and physical activity") in the european union in january 2022. tirzepatide a phase iii clinical trial indicated that tirzepatide could be used for substantial weight loss. specifically, phase-3 clinical trials found that after 71 weeks patients had lost 16% of their starting body weight on average. on 13 may 2022, it was approved under the name mounjaro for type-2 diabetes (though not specifically for weight loss) . exenatide 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 stomach emptying and promotes a feeling of fullness after eating. some people with obesity 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. as of 2015, byetta was recommended only for patients with type 2 diabetes. liraglutide liraglutide (saxenda) is another glp-1 analogue for daily administration, approved 2014. orlistat orlistat (xenical) reduces intestinal fat absorption by inhibiting the enzyme pancreatic lipase. frequent oily bowel movements steatorrhea is a possible side effect of using orlistat. 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. cetilistat cetilistat is a medication designed to treat obesity. it acts in the same way as the older medication orlistat 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. a 2010 phase 2 trial found cetilistat significantly reduced weight and was better tolerated than orlistat. it has not been approved in the us. phentermine/topiramate main article: phentermine/topiramate the combination of phentermine and topiramate, brand name qsymia (formerly qnexa) was approved by the u.s. fda on 17 july 2012, as an obesity treatment complementary to a diet and exercise regimen. in october 2012, the european medicines agency, by contrast, rejected the combination (qsiva) as a treatment for obesity, citing concerns about long-term effects on the heart and blood vessels, mental health and cognitive side-effects. naltrexone/bupropion main article: naltrexone/bupropion naltrexone/bupropion is a combination medication used for weight loss in those that have either obesity or overweight with some weight-related illnesses. it combines low doses of bupropion and naltrexone. both medications have individually shown some evidence of effectiveness in weight loss, and the combination has been shown to have some synergistic effects on weight. in september 2014, a sustained release formulation of the medication was approved for marketing in the united states under the brand name contrave. the combination was approved for use in the european union in march 2015, under the brand name