Number of medications are approved by the US Food and Drug Administration (FDA) for the treatment of overweight or obesity. It is essential that the medications are used in conjunction with healthy eating, physical activity, and behavior modification, as medication usage without such changes are generally ineffective.
The decision to initiate drug therapy in people considered overweight should be made after consideration of the risks and benefits ,and the goals of drug therapy should be clear. This topic will review drug therapy for initial weight loss and for long term weight loss maintenance in patients with obesity. Other treatments for the management of overweight and obesity are discussed elsewhere. .
Goals of therapy
The goal of any treatment (including drug therapy) for people considered overweight is long-term weight reduction and improvement in overall health.
- Reduce weight and maintain weight loss – Contemporary clinical trials evaluating the efficacy of anti-obesity medications have demonstrated 5 to 22.5 percent weight loss when added to lifestyle modification. Upon initiation of anti-obesity medication, we communicate several important messages to patients. First, not every drug works for every patient; individual responses vary widely. Second, when the maximal therapeutic effect is achieved, a plateau is reached and weight loss ceases. This does not mean the drug has “stopped” working. It simply means that additional strategies will be required to induce additional weight loss. Finally, when drug therapy is discontinued, weight regain can be expected. Achieving and maintaining weight loss is made difficult by many factors, including weight loss-induced changes in energy expenditure and hormonal mediators of appetite, which favor weight regain .Therefore, we favor using anti-obesity medications longer term for weight loss maintenance if they are well-tolerated and have yielded clinically meaningful weight loss (>5 percent).
- Improve health status – If improvement in one’s health is the goal, success may be measured by the degree of weight loss and measurable or perceived improvement in physical function, comorbidities, and/or sense of well-being. Weight loss should exceed 2 kg during the first month of drug therapy (1 pound per week), fall more than 4 to 5 percent below baseline between three to six months, and remain at this level to be considered effective. A weight loss of 5 to 10 percent can substantially reduce the development of diabetes in those with prediabetes and reduce blood pressure and risk factors for cardiovascular disease in patients with cardiovascular risk factors. Improvement in health status after weight loss is an important criterion in the determination of whether to continue drug therapy.
- Minimize adverse effects – The potential benefits of weight loss must be considered in light of the potential risks of drug therapy. The longest clinical trial examining the safety and efficacy of pharmacotherapy for weight loss utilized orlistat for four years [12]. Thus, in patients wishing to use anti-obesity medication for longer than four years, the lack of longer-term safety (and efficacy) data should be made known.
What we recommend
Our approach outlined below is based upon the available clinical trial evidence and clinical expertise. Our approach is largely consistent with published guidelines
General principles
- Initial management – Thorough and compassionate counseling around healthy eating, physical activity, and health-seeking behavior is essential for every patient seeking weight loss, whether these lifestyle changes are used alone or in combination with anti-obesity medication or bariatric surgery.
- Approach to underlying comorbidities – An important component of the initial evaluation is the assessment of weight-related comorbid conditions such as diabetes mellitus, dyslipidemia, hypertension, heart disease, sleep apnea, and symptomatic osteoarthritis.
Candidates for drug therapy — Candidates for drug therapy include those individuals with a body mass index (BMI) ≥30 kg/m2, or a BMI of 27 to 29.9 kg/m2 with weight-related comorbidities, who have not met weight-loss goals (loss of at least 5 percent of total body weight at three to six months) with a comprehensive lifestyle intervention alone.
The decision to initiate drug therapy should be individualized, weighing the risks and benefits of all treatment options (lifestyle, pharmacologic, device, surgical).
Choice of agent — Pharmacologic options for the treatment of obesity include the glucagon-like peptide 1 (GLP-1) receptor agonists semaglutide(Wegovy) or liraglutide (by weekly or daily injection, respectively), combination phentermine-extended release topiramate, combination extended-release bupropion-naltrexone, orlistat, phentermine, benzphetamine, phendimetrazine, and diethylpropion .
