Glucagon-like peptide 1 in the pathophysiology and pharmacotherapy of clinical obesity

Table 1 Current and previously Food and Drug Administration licenced anti-obesity pharmacotherapeutics

Drug	Mechanism	Year	Clinical use and limitations	Suspension reason
Currently FDA licenced drugs
Diethylpropion	NA releasing agent	1959	FDA approved for short term use (3 mo); not recommended with uncontrolled hypertension or heart disease	-
Phentermine		1959	FDA and EMA approved for long term use; treatment dependent weight loss	-
Orlistat (Xenical)	-	1999		-
Orlistat (Alli)	Pancreatic lipase inhibitor	2007		-
Phentermine-topamirate (Qysmia)	-	-	Approved for long term use; treatment dependent weight loss	-
Lorcaserin (Belviq)	5HT2c-R antagonist	2012	FDA approved for long term use, recommended in those with cardiovascular disease; treatment dependent weight loss	-
Liraglutide (Saxenda)	GLP-1 analogue	2014	FDA and EMA (2015) approved	-
Previously FDA licenced drugs
Dinitrophenol	Unknown	1938	-	Dermatitis, neuropathy, agranulocytosis, visual impairment, death
Aminorex	Unknown	1968	-	Chronic pulmonary hypertension
Amphetamines	Monoamine reuptake inhibitor	1971	-	Addiction, hypertension, myocardial toxicity
Fenfluramine	Serotonin reuptake inhibitor	1997	-	Valvular heart disease
Phenylpropanolamine	NA-R and DA-R agonist	2000	-	Haemorrhagic stroke
Rimonabant	CB1R antagonist	2009	-	Psychiatric disorders, depression, suicidal ideation
Sibutramine	Serotonin-NA reuptake inhibitor	2010	-	Risk of major cardiovascular events

The pancreatic lipase inhibitor Orlistat and GLP-1 analogue liraglutide are the only currently UK licenced anti-obesity agents). 5HT2c: Serotonin receptor; NA: Noradrenaline; DA: Dopamine; CB1R: Cannabinoid receptor; R: Receptor; FDA: Food and Drug Administration; EMA: European Medical Association.

Table 2 Obesity and endocrine phenotypes in probands with PCSK1 gene deletion monogenic obesity

Ref.	Jackson et al[144], 1997	Jackson et al[143], 2003	Farooqi et al[148], 2007	Frank et al[145], 2013	Parker et al[147], 2013	Bandsma et al[146], 2013
Obesity phenotype
Hyperphagic, early-onset	Yes	Yes	Yes	Yes	Yes	Yes
Endocrine phenotype
Abnormal glucose metabolism	Yes	Yes		Yes	Yes	Yes
Hypogonadotrophic hypogonadism	Yes			Yes	Yes
Hypocortisolaemia	Yes	Yes		Yes	Yes
Hypothyroidism			Yes	Yes	Yes
Central diabetes insipidus					Yes
Others
Early onset malabsorptive diarrhoea	Yes	Yes	Yes	Yes	Yes	Yes

Proband details: Jackson et al[144] (1997) - a 40-year-old Caucasian woman; Jackson et al[143] (2003) - female Caucasian infant, non consanguineous; Farooqi et al[148] (2007) - 6 North African boy, consanguineous; Frank et al[145] (2013) - male infant; Parker et al[147] (2013) - 13 children aged 3 to 17; Bandsma et al[146] (2013) - 2 children age 2 and 7 Arab, consanguineous, 2 children aged 1 and 10, African, non-consanguineous.