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Also: Qnexa · Qsiva · phen-top
Four separate measurements, never averaged. Independent evidence counts only studies with no sponsor attached. Methodology version v2.0-2026-10 · how we grade evidence
Approved in the United States for chronic weight management in adults and in children from 12, available only through a restricted distribution programme under a Risk Evaluation and Mitigation Strategy because of teratogenic risk. Its label makes no cardiovascular claim and explicitly disclaims one.
This compound carries the sharpest regulatory split in the library. The same efficacy dossier was approved by the FDA in July 2012 and refused by the European Medicines Agency twice — a negative opinion in October 2012, confirmed on re-examination in February 2013. The CHMP accepted that the trials showed clinically relevant weight loss and still judged the risks unacceptable, citing cardiovascular risk from phentermine, psychiatric and cognitive effects of topiramate, teratogenicity, and a high probability of off-label use it considered impossible to mitigate.
Meanwhile independent synthesis in 2026 put it at −8.1% body weight, the largest effect of any non-incretin agent assessed. Both of those things are true at once, and this entry exists to show them together rather than pick one.
At a glance
Phentermine is a sympathomimetic amine thought to suppress appetite through catecholamine release in the hypothalamus. Topiramate’s contribution to weight loss is attributed variously to effects on GABA receptors, voltage-gated ion channels, AMPA/kainate glutamate receptors and carbonic anhydrase. The two are combined to allow lower exposure to each than either would need alone. Neither mechanism is established. The FDA label itself states that the exact mechanism of action of phentermine "is not known", and that the precise mechanism of topiramate on weight reduction and long-term maintenance of body weight "is not known". That is the regulator’s own wording, not an inference drawn here.
Dated determinations, each flagged for whether it is final and whether it covers safety only. A safety review is not an efficacy finding, and most reporting in this category conflates the two.
The negative opinion was confirmed on re-examination on 21 February 2013. The product record also shows a refusal date of 14 May 2013, presumably the formal decision. The same efficacy dossier that the FDA approved was refused twice in Europe — the sharpest regulatory split in this library.
The CHMP adopted a negative opinion on 18 October 2012. Grounds: long-term cardiovascular risk from phentermine’s effect on heart rate; long-term psychiatric and cognitive effects of topiramate, including depression, anxiety and memory and attention problems, all reported in the studies; teratogenicity; and a high probability of off-label use with risk-minimisation measures judged impracticable. The committee accepted that the main studies showed clinically relevant weight loss and refused the application anyway.
Approved 17 July 2012 for adults, and extended on 27 June 2022 to patients aged 12 and over with BMI at or above the 95th percentile for age and sex. Dispensing is restricted to certified pharmacies because of teratogenic risk. The label carries an explicit limitation of use: effects on cardiovascular morbidity and mortality have not been established. Ten post-marketing requirements were imposed, including a long-term cardiovascular outcomes trial.
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