Anti-obesity medication or weight loss medications are pharmacological agents that reduce or control weight.
These medications alter either appetite, or absorption of calories.
The main treatment modalities for overweight and individuals with obesity remain dieting with a healthy diet and caloric restriction, and physical exercise.
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.
Lifestyle management is important for obesity treatment but often is associated with weight regain due to counter regulatory physiological changes, that impair metabolism and increase appetite.
Antiobesity, medications are categorized into three groups based on the mechanism of action: intragastrointestinal medications, centrally acting medications, and nutrient stimulated hormone based medications.
Intragastrointestinal medications: Currently only one approved antiobesity medication, orlistat, works by blocking fat absorption in the G.I. tract. In the lumen of the stomach and small intestine, it forms a covalent bond with the active site of intestinal lipases, blocking digestion and absorption approximately 30% dietary fat, leading to caloric deficit.
A cellulose citric acid hydrogel administered like an oral medication and after ingestion expands to occupy 25% of the stomach volume, promoting a sensation of fullness and increased safety.
Centrally acting medications that act on the CNS include phentermine, phentermine – Topiramate , and naltrexone- bupropion.
Phentermine is a sympathomimetic amine that primarily increases nor epinephrine in the hypothalamus with lesser effects on dopamine and serotonin.
It is most commonly used anti-obese medication in this category of drugs.
Phentermine has a low potential for abuse.
Phentermine works through several central mechanisms to reduce appetite and increase satiety.
Naltrexone and bupropion reduce appetite and food cravings through different mechanisms that stimulate propriomelanocortin neurons.
Randomized control studies including 9949 adults with obesity found the combination of agents associated with a 4.1% greater weight loss than placebo.
Combining naltrexone with bupropion and intensive behavioral therapy is associated with a 9.3% weight loss at 12 months compared with 5.1% weight loss for placebo with intensive behavioral therapy.
Naltrexone and bupropion have fewer cardiac effects on risk factors than does other anti-obese medications.
Naltrexone and bupropion have fewer cardiac effects on risk factors than does some other anti-obese medications.
Common and effects of N-B include nausea, constipation, headache, vomiting, dizziness, insomnia, and xerostomia.
Nutrient-stimulated hormone based medications have a role in the gut – brain axis in controlling appetite, to stimulate metabolic effects of naturally occurring into pancreatic hormones, including glucagon like peptide (GLP – 1) glucose dependent insulinotropic polypeptide (GIP) glucagon, and amylin.
GLP –1 receptor agonists have an incretin effect amplifying insulin secretion after oral vs intravenous administration in other cardiometabolic actions with decreasedblood pressure and inflammation mediated by its widespread distribution of receptors throughout the body.
In addition to appetite suppression GIP receptors exist in adipose tissue to promote lipoprotein lipase activation.
Glucagon enhances hepatic lipolysis and may increase energy expenditure.
Amylin enhances leptin sensitization and has direct brain activation to promote meal ending satiety.
The three nutrients stimulating hormone based anti-obesity medications include :liraglutide, semaglutide and tirzepatide.
Liraglutide, in a metaanalysis of 18 randomizedcontrol trials including 6321 participants reported that it was associated with a 4.7% weight loss reduction among adults with obesity, compared to placebo.
Medication adherence declined overtime at 52% at three months, and 17% at 12 months.
The most common adverse effects associated with their liraglutide was nausea (39%), diarrhea (21%) and constipation (19%), which are mild to moderate.
Glucagon-like peptide-1 (GLP-1) are peptide incretin hormones involved in blood sugar control.
Semaglutide Semaglutide (Ozempic, Wegovy ) GLP-1 analogue, administered once weekly-more effective than exenatide.
Tirzepatide (Mounjaro)
After 71 weeks patients had lost 16% of their starting body weight on average. Exenatide (Byetta) is a long-acting analogue of the hormone GLP-1, which the intestines secrete in response to the presence of food.
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.
Liraglutide (Saxenda) is another GLP-1 analogue for daily administration.
Orforglipron is a non-peptide GLP-1 agonist of potential interest because it can be taken orally and is chemically simpler and thus potentially cheaper than peptides such as semaglutide.
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.
Cases of severe liver injury that have been reported rarely with the use of this medication.
Cetilistat inhibits pancreatic lipase, an enzyme that breaks down triglycerides in the intestine; triglycerides from the diet are prevented from being hydrolyzed into absorbable free fatty acids and are excreted undigested.
The combination of phentermine and topiramate, brand name Qsymia an obesity treatment complementary to a diet and exercise regimen.
Naltrexone/bupropion is a combination medication used for weight loss in those that have either obesity or overweight with some weight-related illnesses.
Naltrexone/bupropion combined low doses of bupropion and naltrexone.
Gelesis100 (Plenity”) is an oral superabsorbent hydrogel used for weight loss in the treatment of obesity and overweight.
Gelesis100 absorbs water, expands in the stomach and small bowel, which may result in satiety: use of Gelesis100 be limited to clinical trials due to limited evidence.
Gelesis100 was approved in April 2019 by the US Food and Drug Administration as a medical device. In 2022, the American Gastroenterology Association recommended the use of Gelesis100 be limited to clinical trials due to limited evidence.
In people with type 2 diabetes mellitus and for those taking clozapine for schizophrenia, the medication metformin (Glucophage) can reduce weight, but in others it is not approved as an anti-obesity medication.
Metformin limits the amount of glucose that is produced by the liver as well as increases muscle consumption of glucose, and helps in increasing the body’s response to insulin.
Some anti-obesity medications can have severe, even, lethal side effects: fenphen.
Fen-phen was reported through the FDA to cause abnormal echocardiograms, heart valve problems, and rare valvular diseases.
Another medication, orlistat, blocks absorption of dietary fats, and as a result may cause oily spotting bowel movements, steatorrhea, 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.
Retatrutide is an agonist of the glucose dependent insulinnotropic polypeptide, glucagon like peptide1, and glucagon receptors.
In adults with obesity retatrutide treatment for 48 weeks resulted in substantial reduction in body weight.
A concern with anti-obesity medicines is the ability to maintain lean body mass (muscle mass) during weight loss that is important for mobility and physical function, particularly among older adults who have lower lean body mass due to aging.
Physical activity should be maintained with the integration of resistance training to decrease lean body mass loss and enhance strength and mobility.
Anti-obesity medication adherence in clinical practice is poor, and weight loss is common when these drugs are discontinued.