Table 3.

Drugs used in the pharmacotherapy of obesity [14,95].

			Orlistat	Liraglutide, Semaglutide †	Naltrexone/Bupropion	Phentermine/Topiramate	Phentermine ‡
mechanism of action [20]			gastric/pancreatic lipase inhibitor	GLP1 receptor agonist	opioid receptor antagonist + NDRI	sympathomimetic + CAI and GABA/amine modulator	sympathomimetic
route of administration			oral	subcutaneous	oral	oral	oral
target dose			120 mg	3.0 mg (lirglutide) 2.4 mg (semaglutide)	16 mg/180 mg	15 mg/92 mg	15 mg
dosage frequency			three times daily	once daily (liraglutide)once weekly (semaglutide)	twice daily	once daily	once daily
long-term weight change vs. placebo		%	−4.0% [14], −2.9% [95]	liraglutide: −4.0% [14], −5.4% [95], from −6.0% to −8.0% [20] semaglutide: −15.8% * [111]	−4.2% [14], −4.8% [95], from −8.2% to −11.5% [20]	−8.6% [14], −7.3% [112], −9.4% [113] §, from −5.1% to −10.9% [20]	−4.9% [14] (short-term effect)
		kg	−2.8 kg, −3.0 kg [20]	liraglutide: −4.2 kg; −6.8 kg * [111] semaglutide: −15.3 kg * [111]	ND	−6.4 kg [112]	ND
change in T2DM development risk			↓ (−37.3%)	↓ (−79.0%)	ND	ND	ND
effect on HbA1c [mmol/mol]			−4.4	−10.9	−5.5	ND	NC/NS [114]
effect on lipids	TC		↓	↓	ND	↓ [112,113]	NC/NS [114]
	LDL		↓	↓	↓	↓ [112,113]	NC/NS [114]
	non-HDL		ND	↓	ND	ND	ND
	HDL		NC/NS	↑	↑	NC/NS [112]/↑ [113]	NC/NS [114]
	TG		NC/NS	↓	↓	NC/NS [112]/↓ [113]	NC/NS [114]
cost of therapy (per month)			$$	$$$$	$$$	$$	$

T2DM—diabetes mellitus type 2; NDRI—norepinephrine and dopamine reuptake inhibitor; CAI—carbonic anhydrase inhibitor; ND—no data; NC/NS—no change or not significant; TC—total cholesterol; LDL = low-density lipoprotein; HDL—high-density lipoprotein; TG—triglyceride; beneficial effect highlighted in green; non-conclusive data on beneficial effect highlighted in yellow. Lorcaserin and lorcaserin SR were not included in the comparison due to drug approval being withdrawn by the FDA as of 13 February 2020 [15]. All data are based on [14,95], unless otherwise stated. ^† Liraglutide and semaglutide are the only drugs currently approved for therapy of both diabetes mellitus type 2 and obesity. ^‡ Alone, phentermine is approved only for short-term obesity management (≤12 weeks). * Not adjusted for placebo [111]. ^§ Based on analysis A (prespecified ITT-LOCF—Intent to Treat population Using the Last Observation Carried Forward Method). ↑ = an increase, ↓ = a decrease. The number of $ symbols correspond to the cost of the drugs.