Phentermine and topiramate for the management of obesity: a review

Figures & data

Figure 1 Phentermine.

Note: C₁₀ H₁₅ N formal chemical name (IUPAC): 2-methyl-1-phenylpropan-2-amine.

Figure 2 Topiramate.

Note: C₁₂H₂₁NO₈S, formal chemical name (IUPAC): [(3aS,5aR,8aR,8bS)-2,2,7,7-tetramethyl-5,5a,8a,8b-tetrahydrodi[1,3]dioxolo[4,5-a:5′,3′-d]pyran-3a-yl]methyl sulfamate.

Table 1 Oral agents for potential combination therapy in obesity management

Name	Medication class	Mode of action for weight management	Side effects/ safety profile concerns	FDA approval status	Combinatorial trials	Typical net weight loss (kg)
Orlistat	Lipase inhibitor	Reducing bowel based fat absorption	+	Approved for obesity rx, available OTC	With Sibutramine, metformin and phentermine	~2.3
Sibutramine	B-phenethylamine	Appetite suppressant and increased energy expenditure	++++	Pulled from the US market; 2010	With orlistat	~3.5
Phentermine	Sympathomimetic	Appetite suppressant	++	Approved for short term obesity rx	With orlistat and topiramate	~4
Diethylpropion	Sympathomimetic	Appetite suppressant	++	Approved for short term obesity rx	–	~3
Benzphetamine	Sympathomimetic	Appetite suppressant	++	Approved for short term obesity rx	–	~2.5
Phendimetrazine	Sympathomimetic	Appetite suppressant	++	Approved for short term obesity rx	–	~2.5
Naltrexone	Partial opioid antagonist	? altered satiety perception	++	Approved for alcohol dependence	With bupropion	~1.6
Buproprion	Antidepressant	? altered satiety perception	++	Approved for smoking cessation	With naltrexone and zonisamide	~3.2
Rimonabant	Cannabinoid antagonist	? altered satiety perception	+++	Pulled from the market in Europe; 2007	–	~6.5
Topiramate	Antiepileptic	? appetite suppressant ? altered satiety perception	+++	Approved for epilepsy and migraine rx	With phentermine and rimonabant	~2.8
Zonisamide	Antiepileptic	? appetite suppressant ? altered satiety perception	+++	Approved for epilepsy rx	With bupropion	~7.5
Metformin	Biguanide antidiabetic	Unclear? Mild anorexiant	+	Approved for diabetes and PCOS rx	With orlistat and rimonabant	~2
Lorcaserin	Sympathomimetic	Appetite suppressant; serotonin 2c agonist	+++	Approved for monotherapy of obesity	–	~3.7

Abbreviations: OTC, over-the-counter; PCOS, polycystic ovary syndrome.

Table 2 Identified and putative modes of action of topiramate peripherally and centrally^65,66

Receptor/substrate	Activity	Distribution of activity
1. Gamma aminobutyric acid receptor (α-1 subunit)	Agonist	Central
2. Sodium ion channel (α-1 subunit)	Antagonist	Central and peripheral
3. Carbonic anhydrase 2 and 4	Inhibitor	Systemic
4. Glutamate ionotropic kainate type 1	Antagonist	Central
5. Cytochrome P450 2C19	Inhibitor	Systemic
6. Cytochrome P450 3A4	Inducer	Systemic
7. Calcium α-1 subtype cellularion channel	Antagonist	Central and peripheral
8. ATP activated anion channel (CFTR)	Antagonist	? systemic

Abbreviations: ATP, adenosine triphosphate; CFTR, cystic fibrosis transmembrane condulence regulator.

Table 3 Clinical approval trials for Qsymia

Trial name	Number of patients	Study population	Medication treatment arms	Study duration	Mean % weight loss from baseline (in maximum dose group)	% of subjects with at least 5% weight loss (in maximum dose group)	% of subjects with at least 10% weight loss (in maximum dose group)
EQUIP^Citation47	1267	BMI ≥ 35	3.75/23 mg and 15/92 mg	56 weeks	14.4	67	47
EQUATE^Citation81,Citation82	756	Non diabetic, BMI ≥ 35	7.5/46 mg 15/96 mg and 7.5 and 15 mg alone of phentermine as well as 46 and 92 mg alone of topiramate	28 weeks	9.2		40.8
CONQUER^Citation45	2487	BMI ≥ 27 and ≤45 ± clinical comorbidities	7.5/46 mg and 15/92 mg	56 weeks	12.4	70	48
SEQUEL^Citation46	676	Same as CONQUER	Same as CONQUER	2 yrs	10.5	79.3	53.9
FORTRESS^Citation83,*	*	*	*	*	*	*	*

Note:

* Retrospective case control comparison study of pregnancy related teratogenic risk potential.

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