Anti-obesity drugs currently used and new compounds in clinical development

Table 1 Benefits and risks of anti-obesity drugs

Drug	Drug/Placebo subtracted weight loss	Mechanism of action	Other positive effects	Adverse effects
Orlistat (Xenical®)	3.6%	Decreases fat absorption	Improvement in most risk factors of cardiovascular disease and CRP	Increased flatulency Fecal incontinence Diarrhea
Lorcaserin (Belviq®)	3.6%	5-HT2C receptors agonist	Reduction in energy intake and appetite. Improvement in the markers of cardiovascular disease and inflammation	Headache, fatigue, dizziness, nausea, dry mouth, constipation. Disturbances in attention or memory. Risk of birth defects
Phentermine 7.5 + Topiramate 46 (QsymiaTM)	6.6%	Amphetamine analogue + Anticonvulsivant	Improvement of cardiometabolic variables	Psychiatric and cognitive adverse effects. Risk of birth defects
Phentermine 15 + Topiramate 92	8.6%
Cetilistat	1.46 kg	Decreases fat absorption	Improvement in glycemic control	Mild or moderate gastrointestinal effects
Naltrexone 16 + Bupropion (Contrave®)	4.9%	µ-opioid antagonist + Stimulator of the hypothalamic POMC neurons	Improvement in cardiometabolic risk factors and in insulin resistance	Nausea, constipation, anxiety, increase in blood pressure
Naltrexone 32 + Bupropion	6.3%
Zonisamide 120 + Bupropion (EmpaticTM)	4.7%	Increases monoamines (e.g., DA) and POMC neurons activity	Reduction in appetite. Increase in energy expenditure	Headache, nausea, insomnia
Zonisamide 360 + Bupropion	6.1%
Tesofensine	5.4 ± 6.7 kg	Inhibits reuptake of DA, 5-HT and NE	Reduction in appetite, body fat and waist circumference	Increase in heart rate and blood pressure
Liraglutide (Victoza®)	0.5 ± 0.3 kg	GLP-1 agonist; increases insulin secretion after meals	Improvement in glycemic control and systolic blood pressure	Nausea, diarrhea, vomiting
Exenatide (Byetta®)	3.5 ± 0.5 kg	GLP-1 agonist; increases insulin secretion after meals	Improvement in glycemic control and systolic blood pressure	Nausea, diarrhea
Pramlintide (Symlin®)	1.5% ± 0.7%	Anti-hyperglycemic agent; synthetic analogue of human amylin	Reduction in binge eating tendencies and blood pressure	Nausea

5-HT: 5-hidroxytryptamine; 5-HT_2C: 5-hidroxytryptamine 2C receptors; CNS: Central nervous system; CRP: C-reactive protein; DA: Dopamine; GLP-1: Glucagon-like peptide 1; NE: Norepinephrine; POMC: Pro-opiomelanocortin.