section_path: Medical interventions/Medication
section_name: Medication
paragraph_text: Medication
  
  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 Out of 25 anti-obesity medications withdrawn from the market between 1964 and 2009, 23 acted by altering the functions of chemical neurotransmitters in the brain.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.
  
  Five medications beneficial for long-term use are: orlistat, lorcaserin, liraglutide, phentermine–topiramate, and naltrexone–bupropion. They result in weight loss after one year ranged from 3.0 to 6.7 kg (6.6-14.8 lbs) over placebo. Orlistat, liraglutide, and naltrexone–bupropion are available in both the United States and Europe, phentermine–topiramate is available only in the United States. European regulatory authorities rejected lorcaserin and phentermine-topiramate, in part because of associations of heart valve problems with lorcaserin and more general heart and blood vessel problems with phentermine–topiramate. Lorcaserin was available in the United States and then removed from the market in 2020 due to its association with cancer. Orlistat use is associated with high rates of gastrointestinal side effects and concerns have been raised about negative effects on the kidneys. There is no information on how these drugs affect longer-term complications of obesity such as cardiovascular disease or death; however, liraglutide, when used for type 2 diabetes, does reduce cardiovascular events.
  
  In 2019 a systematic review compared the effects on weight of various doses of fluoxetine (60 mg/d, 40 mg/d, 20 mg/d, 10 mg/d) in obese adults. When compared to placebo, all dosages of fluoxetine appeared to contribute to weight loss but lead to increased risk of experiencing side effects such as dizziness, drowsiness, fatigue, insomnia and nausea during period of treatment. However, these conclusions were from low certainty evidence. When comparing, in the same review, the effects of fluoxetine on weight of obese adults, to other anti-obesity agents, omega-3 gel and not receiving a treatment, the authors could not reach conclusive results due to poor quality of evidence.
  
  Among antipsychotic drugs for treating schizophrenia clozapine is the most effective, but it also has the highest risk of causing the metabolic syndrome, of which obesity is the main feature. For people who gain weight because of clozapine, taking metformin may reportedly improve three of the five components of the metabolic syndrome: waist circumference, fasting glucose, and fasting triglycerides.