Table 1.

Pharmacological agents used for weight loss in human studies.

Agent	Mechanism of action	Status
A) Classical centrally acting anorexiant agents
Phenylpropanolamine54	Primarily adrenergic agents	Withdrawn (increased risk of hemorrhagic stroke).
Phentermine51		Approved for short-term use in adults.
Diethylpropion44		Approved for short-term use in adults .
Mazindol45,53		Approved for short-term use in adults; not currently available in US.
Amphetamine70–71	Primarily dopaminergic agent	Not approved for obesity treatment.
Fenfluramine, dexfenfluramine51, 62, 65	Primarily serotonergic agents	Voluntarily withdrawn (valvular heart disease, pulmonary hypertension).
Sibutramine87–89	Mixed adrenergic-serotonergic agent	Voluntarily withdrawn (increased risk of serious, nonfatal cardiovascular events).
B) Drugs in development or used off-label that may act centrally as anorexiant medications
Recombinant human leptin, metreleptin101, 102	Leptin receptor agonists	Investigational. In monotherapy successful for treatment of leptin deficiency.
Bupropion114, 117	Mixed dopaminergic and adrenergic reuptake inhibitor	Not FDA-approved for obesity.
Tesofensine126–128	Adrenergic/dopaminergic reuptake inhibitor	Investigational.
Lorcaserin121, 122	Highly selective serotonergic 5-HT2C receptor agonist	FDA-approved as an anti-obesity drug in June 2012.
Fluoxetine61, 205	Selective Serotonin reuptake inhibitor	Not FDA-approved for obesity.
Rimonabant, Taranabant130,134	Cannabinoid receptor-1 inhibitors	Never FDA-approved.
Topiramate139, 140	GABA-receptor activator, kainite/AMPA glutamate receptor inhibitor	Not FDA-approved for obesity. Concerns about teratogenicity and cognitive effects.
Pramlintide153	Amylinomimetic	Not FDA-approved for obesity.
Liraglutide, Exenatide162–166, 294, 295	GLP-1 analogues	Not FDA-approved for obesity.
Sitagliptin, Vildagliptin296,297	Dipeptidyl peptidase inhibitor-4	Not FDA-approved for obesity.
Peptide YY298,299	Acts on Y2 receptor	Investigational.
C) Drugs affecting nutrient trafficking
Orlistat171–177		FDA-approved for treatment of obesity in adolescents ≥12 years old.
Cetilistat186, 187	Gastrointestinal lipase inhibitors	Not FDA-approved for obesity.
Acarbose190–192	Intestinal α-glucosidase inhibitor	Not FDA-approved for obesity.
Dapagliflozin196–199, 300 Sergliflozin193–195, 300	Renal sodium-glucose cotransport inhibitors	Investigational.
D) Drugs affecting internal milieu/metabolic control
Metformin213, 206, 218	AMP-activated protein kinase activation	Not FDA-approved for obesity.
Octreotide224,225	Somatostatin analogue	Not FDA-approved for obesity. Weight stabilization in hypothalamic obesity.
Recombinant human growth hormone234	Growth hormone receptor agonist	Not FDA-approved for obesity.
Thyroid hormone244	Sympathomimetic	Not FDA-approved for obesity. Not recommended - risk of sudden death.
Ephedrine + Caffeine253,254, 261	Sympathomimetic + nonselective antagonist of adenosine receptors	Never FDA-approved for obesity Ephedrine withdrawn from market.
E) Novel combination therapies in development
Phentermine+Topiramate265, 266	Norepinephrine-releasing agent+GABA-receptor activator, kainite/AMPA glutamatereceptor inhibitor	FDA-approved as an anti-obesity drug in July 2012.
Bupropion+Zonisamide269	Norepinephrine/dopamine reuptake inhibitor+GABA-receptor activator	Investigational.
Bupropion+Naltrexone274, 276	Norepinephrine-dopamine reuptake inhibitor+ opioid receptor antagonist	Investigational.
Pramlintide+Metreleptin154, 280, 281	Amylinomimetic + leptin receptor agonist	Investigational.
Pramlintide+Phentermine or Sibutramine283	Amylinomimetic + norepinephrine releasing agent/ serotonergic and adrenergic reuptake inhibitor	Investigational.