Phentermine and topiramate extended-release: a new treatment for obesity and its role in a complications-centric approach to obesity medical management

Abstract

Introduction: Weight-management options include lifestyle modifications, bariatric surgery and, until recently, limited pharmacotherapy. (phentermine/topiramate ER) has recently been approved in the USA for chronic weight management in obese adults and overweight adults with weight-related co-morbidities in conjunction with a reduced-calorie diet and increased physical activity.Areas covered: This review describes the pharmacology and clinical trials data for phentermine/topiramate ER and its role in a complications-centric approach to medical care of the overweight and obese patient.Expert opinion: Phentermine/topiramate ER is an effective and safe weight-loss medication that can produce and sustain approximately 10% loss of body weight. This is a landmark development in the pharmacotherapy of obesity. By offering an effective medical option to complement lifestyle and surgical approaches, phentermine/topiramate ER enables a comprehensive medical model for obesity care. The overall approach to the overweight and obese patient should be to identify individuals who will benefit most from therapy based on cardiometabolic or mechanical complications, establish therapeutic targets and goals for ameliorating these complications and selecting the treatment modality and intensity for weight loss to achieve these goals. This complications-centric model emphasizes weight loss as a tool to ameliorate obesity-related complications and optimizes benefit/risk for achieving the best outcomes in overweight/obese patients.

Weight maintenance: challenges, tools and strategies for primary care physicians

“…These effects help patients sustain weight loss and help them comply with calorie‐reduced diets. Clinical trials have shown that the addition of pharmacotherapy to lifestyle interventions promotes greater weight loss and sustains weight loss for a longer period of time than lifestyle interventions alone 13, 96, 97, 99, 100, 116. The available data, while only encompassing ≤2 years of follow‐up, demonstrate that these pharmacotherapies sustain weight loss while patients randomized to lifestyle interventions plus placebo are regaining weight (Table 1) 13, 96, 97, 99, 100, 116.…”

New Tools for Weight-Loss Therapy Enable a More Robust Medical Model for Obesity Treatment: Rationale for a Complications-Centric Approach

“…Phentermine/topiramate ER is an oral combination of immediate-release phentermine hydrochloride and ER topiramate (25). Phentermine is a sympathomimetic amine anorectic agent approved in 1959 for the short-term treatment of obesity at a dose of 30 mg (free base) by mouth once a day.…”

“…Although the drug augments gabaminergic transmission, inhibits α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor/kainite excitatory glutamate receptors and has carbonic anhydrase activity, the mechanism by which topiramate causes weight loss is unknown. Phentermine/topiramate ER combines lower doses of phentermine and an ER form of topiramate in a once-daily pill to achieve synergism with respect to weight loss at lower adverse event rates when compared with higher doses of these individual medications (25). …”

“…An average weight loss of ~10%, achievable with the new weight-loss drugs, will not suffice cosmetically or even bring many patients below the BMI threshold for obesity (i.e., BMI <30 kg/m 2 ); however, this degree of weight loss is sufficient to exert powerful benefits regarding obesity complications. This brings us to the third point, which is that moderate weight loss (~10%) is sufficient to lower fasting glucose and insulin, enhance insulin sensitivity, reduce blood pressure, lower triglycerides, raise HDL-c, decrease levels of hepatic transaminases, prevent progression to diabetes, lower HbA1c in patients with T2DM while at the same time reducing the requirements for diabetes medications, and improve biomarkers of cardiovascular risk, such as CRP, fibrinogen, and adiponectin (4,9,12–16,25,27–36). In patients with T2DM, weight loss of ~10% can improve control of glycemia and blood pressure, concomitant with reductions in the dose and number of diabetes and hypertension medications (15,25,29,30,36,37).…”

A Complex Systems Approach to Perceptions of Obesity in Service Users, Health Care Practitioners and Policy Makers

“…Bariatric surgery can be highly effective for weight-loss, but access for patients can be limited due to long wait lists, high costs and variable follow-up care (34). Additionally, the invasive nature of surgery can result in a range of adverse events and mortality related to the procedures (34,35). Pharmaceuticals and bariatric surgery are also infrequently recommended by physicians as a weight loss approach (36).…”