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Learn more Accept. Contact us for any additional information For any question, information or reservation please contact us through the contact form below. Similarly, patients showed significant, sustained percentage and categorical weight loss through weeks in the 2-year cohort of the SEQUEL extension study [87]. Changes in a blood pressure, b heart rate, and c rate pressure product from baseline to week 56 1-year cohort; safety set [88,89].

Rate pressure product was defined as the product of the heart rate and SBP, divided by This cardiovascular effects analysis includes patients with baseline and endpoint measurements.

Effects on heart rate at week 56 based on baseline heart rate 1-year cohort; safety set [88]. The slight mean increases in heart rate vs. Increased myocardial oxygen demand is the putative mechanism by which increased heart rate promotes cardiac ischaemia in patients with macrovascular or microvascular coronary disease [94].

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Change in blood pressure, heart rate, and rate pressure product in patients with hypertension at baseline 1-year cohort; safety set [92]. Adverse events were generally dose-related and mild to moderate in severity, occurring mostly during the titration period [26,84,86—88]. Cardiac arrhythmia-related adverse events reported by patients as defined by mapping to the Medical Dictionary for Regulatory Activities Cardiac Disorders System Organ Class were palpitations, increased heart rate, and tachycardia, and occurred in between 0.

There were low rates of serious adverse events classified as cardiac disorders [92]. Within the 1-year safety cohort, A cardiovascular outcomes trial is planned by the drug's manufacturer, in accordance with one of the US FDA's post-marketing study requirements [95].

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Incidence rates for cardiovascular event outcomes MACE endpoints; all exposed patients [92]. There is a current unmet need for an effective weight-loss pharmacotherapy that can be used for long term for the many patients unable to attain or to maintain weight loss through dietary interventions and exercise.

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Given the increased cardiovascular and metabolic risk in this patient population, obesity pharmacotherapies must present minimal unwanted or adverse cardiovascular risks, which if present, should be outweighed by their other cardiovascular-related benefits. However, the treatment is not without side effects.


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For example, the topiramate extended-release component can induce paraesthesia and taste change, likely through carbonic anhydrase inhibition. Topiramate cannot be used by pregnant women due to teratogenic risks. The phentermine component can produce adrenergic symptoms, such as dry mouth. We would like to acknowledge and thank The Lockwood Group for editorial assistance. This review showed that combining low doses of phentermine and topiramate for the treatment of obesity minimized side effects while maintained weight loss efficacy.


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  • The side effects were paraesthesia, taste changes and dry mouth. Weight loss induced by the combination was associated with improved BP through one and two years of treatment. A small, usually transient increase in heart rate was observed. However, reductions in BP and rate pressure product were seen suggesting that when used in conjunction with lifestyle modifications, the combination may represent a safe and effective therapy for the management of obesity.

    A large multinational trial concerning cardiovascular outcomes is ongoing. Combination drug treatment based on phentermine and topiramate has been recently approved by the FDA for the treatment of overweight and obesity. The paper by Jordan et al. The information available so far on the impact the drug has on cardiovascular events limited at present at the one year follow-up confirms the favourable effects the drug has on cardiovascular risk.

    Abbreviations: BP, blood pressure; b. National Center for Biotechnology Information , U. Journal of Hypertension. J Hypertens. Published online Apr Day , d and Nick Finer e. Wesley W. Author information Article notes Copyright and License information Disclaimer. The work cannot be changed in any way or used commercially. This article has been cited by other articles in PMC. Abstract Weight loss can reduce the increased cardiovascular risk associated with obesity.

    Keywords: cardiovascular risk, obesity, phentermine, topiramate. Agent Year s History of cardiovascular effects Dinitrophenol s Affected mitochondrial oxidative phosphorylation to induce weight loss, and was associated with elevated body temperature [27,39]. Amphetamines s Linked to increased risk of hypertension and pulmonary hypertension [29].

    Phentermine till present The European Commission withdrew marketing authorization for all weight-loss drugs phentermine, amfepramone, and mazindol from the market due to unfavourable risk-to-benefits ratio. The licence was withdrawn and then subsequently reinstated several times [38] , but a decision in by the European Court of First Instance overturned previous decisions to withdraw marketing authorizations for phentermine [37].

    Phentermine is eligible for marketing authorization, but would require an updated application to be submitted.

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    Fenfluramine and dexfenfluramine Fenfluramine: —; dexfenfluramine: — Fenfluramine or dexfenfluramine used in combination with phentermine until fenfluramine and dexfenfluramine were withdrawn from the market in September due to links to pulmonary hypertension and valvulopathy [28,30—33]. Aminorex — An amphetamine analogue, withdrawn due to risks of pulmonary hypertension [27]. Sibutramine — Norepinephrine and serotonin-reuptake inhibitor was approved for treating obesity in the US and in Europe.

    Due to increased SBP, DBP, and pulse, caution was recommended in people with poorly controlled hypertension or history of cardiovascular arterial disease, stroke, or arrhythmia hyperthermia [27,39]. Phenylpropanolamine Withdrawn from the US market due to increased risk of haemorrhagic stroke [27].


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    • Ephedrine Withdrawn from the US market due to adverse cardiovascular effects [27]. Open in a separate window. CV, cardiovascular. Treatment of obesity and associated cardiovascular effects Phentermine is the most widely used weight-loss pharmacotherapy in the US [52] ; phentermine HCl, an immediate-release formulation that undergoes rapid dissolution and absorption in the gastrointestinal tract, is currently approved for use at a dose of Changes in rate pressure product 1-year and 2-year cohorts, safety set Increased myocardial oxygen demand is the putative mechanism by which increased heart rate promotes cardiac ischaemia in patients with macrovascular or microvascular coronary disease [94].

      TABLE 3 Change in blood pressure, heart rate, and rate pressure product in patients with hypertension at baseline 1-year cohort; safety set [92]. Cardiac events in all exposed patients Within the 1-year safety cohort, Conflicts of interest J. Reviewer 2 Combination drug treatment based on phentermine and topiramate has been recently approved by the FDA for the treatment of overweight and obesity. Footnotes Abbreviations: BP, blood pressure; b. World Health Organization Obesity and overweight fact sheet No WWW document ; Nguyen T, Lau DC.

      The obesity epidemic and its impact on hypertension. Joint statement of the European Association for the Study of Obesity and the European Society of Hypertension: obesity and difficult to treat arterial hypertension. Secular trends in deaths from cardiovascular diseases: a year community study. Circulation ; — [ PubMed ] [ Google Scholar ]. Changes in risk factors and the decline in mortality from CVD. The Framingham Heart Study. Ford ES, Capewell S. Proportion of the decline in CV mortality disease due to prevention vs.