Anti-obesity medication

Anti-obesity medication or weight loss medications are

• 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in a region of the brain called the hypothalamus.^[10] Lorcaserin (Belviq) was FDA approved for weight loss but was withdrawn from the market because a safety clinical trial shows an increased occurrence of cancer.^[11]
• 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 However, some drugs in this class such as rimonabant were withdrawn or ceased development to concerns about mental health and suicide.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

• 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
  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]
• thermogenic effects of thyroid hormones with fewer adverse effects, but none have received approval as of 2023.^[15]

• 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]
• 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

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

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]

Withdrawn

Never approved

Safety and side effects

Some anti-obesity medications can have severe, even, lethal side effects,