Article
As the prevalence of obesity continues to increase and treatment strategies evolve, pharmacists are not only in a position to advise on appropriate use of pharmacotherapy for obesity, but also to assist in improving outcomes from gastric bypass surgery.
The evolving role of pharmacists in current management of obesity was discussed by Emily Armstrong, PharmD, BCACP; Kathryn Hurren, PharmD, BCACP; and Katie McClendon, PharmD, BCPS.
The prevalence of obesity has increased from 13% in the 1980s to nearly 40% today. Although the prevalence rate has leveled off in recent years, the 2013 decision of the American Medical Association to classify obesity as a disease highlights the importance of this condition.
Along with the growth in the prevalence of obesity, the consequences of obesity are also increasing in prevalence. Obesity, which is implicated in 18% of deaths in the United States, worsens many related medical conditions including type 2 diabetes mellitus (T2DM), obstructive sleep apnea, coronary heart disease, hypertension, and asthma.
For patients in need of moderate weight reduction beyond the levels possible with lifestyle interventions alone, pharmacotherapeutic intervention may be considered. Long-term data are available for 2 agents, lorcaserin and phentermine/topiramate. Older agents such as phentermine and diethylpropion were approved in the 1960s based on data from short-term trials of about 15 weeks in duration. Contrasting with the data available for older agents, 2 years of efficacy and safety data are available for lorcaserin and phentermine/topiramate.
The need for additional data and safety monitoring is understandable given previous withdrawals of weight loss drugs from the market (ie, rimonabant, fenfluramine/dexfenfluramine, and sibutramine).
A series of 3 phase 3 trials led to the approval of lorcaserin. Two trials, BLOOM and BLOSSOM, lasted 1 year each. BLOOM-DM, an extension of BLOOM, evaluated the safety and efficacy of lorcaserin in patients with T2DM. The completion rates were 50% to 66%. Compared with placebo, the average percentage of total body weight lost after 1 year was 3.6 percentage points greater in patients who received lorcaserin.
As with lorcaserin, the approval of phentermine/topiramate was based on 3 studies. Two trials, EQUIP and CONQUER, were 1 year in duration each. SEQUEL, which was a 1-year extension of CONQUER, evaluated long-term safety and efficacy. The completion rates were 60% to 69%. Compared with placebo, the average percentage of total body weight lost after 1 year was 7 to 9 percentage points greater in patients who received phentermine/topiramate.
In the absence of direct head-to-head trials, phentermine/topiramate appears to offer greater efficacy than lorcaserin due to a greater magnitude of effect with phentermine/topiramate. The greater efficacy of phentermine/topiramate compared with lorcaserin was evident despite enrollment of higher—body mass index (BMI), higher–cardiovascular risk patients in trials evaluating phentermine/topiramate compared with patients enrolled in trials evaluating lorcaserin.
Common adverse events associated with the use of lorcaserin included headache, fatigue, dizziness, back pain, and hypoglycemia. With phentermine/topiramate, common adverse events included paraesthesias, dry mouth, constipation, insomnia, and dizziness. Phentermine/topiramate and lorcaserin were not associated with any statistically significant increase in the risk of depressive symptoms or valvulopathy.
Surgical interventions are an option for patients with a BMI of 40 kg/m2 or greater, or patients with a BMI of 35 kg/m2 or greater and a major weight-related comorbidity. In patients who are undergoing surgical intervention, the presenters identified opportunities for pharmacists to help manage the pharmacotherapeutic regimen before, during, and after gastric bypass.
Pharmacists should encourage discontinuation of estrogens in the 3 to 4 weeks leading up to surgery. Doing so may reduce the risk of venous thromboembolism. Immediately before surgery, pharmacists should help ensure appropriate antimicrobial prophylaxis. After surgery, pharmacists may encourage changes to antidiabetic therapy and help prevent vitamin deficiencies.
In patients who have undergone gastric bypass surgery, the activity of various medications may change. For instance, enalapril may be less effective in patients with a smaller stomach volume due to a diminished opportunity for enalapril to form its active metabolite, as this metabolic conversion normally occurs in the stomach. In patients taking enalapril, pharmacists may recommend a different antihypertensive medication. Similarly, because the antifungal medication ketoconazole is absorbed primarily in the stomach, the use of an alternative antifungal may be necessary in patients with a reduced gastric volume.
A reduced gastric volume may also increase the risk of adverse events with some medications. Oral bisphosphonates and nonsteroidal anti-inflammatory drugs (NSAIDs) may be more likely to cause ulceration. Alternatives include intravenous bisphosphonates and topical NSAIDs.
Further complicating medication adjustments, levels of other medications, including lamotrigine, olanzapine, quetiapine fumarate, sertraline, and many extended-release medications, may change after gastric bypass surgery; careful monitoring may be required.
Pharmacists play an important role in recommending lifestyle changes and medication therapy adjustments for patients with increased cardiovascular risk due to obesity. Pharmacists may also help adjust the pharmacotherapeutic regimen before and after gastric bypass surgery to ensure that patients are receiving optimal medication therapy at all stages.
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