Clinical Review

Obesity Management: Clinical Review and Update of the Pharmacologic Treatment Options

The toolbox of medications available for medical weight management is more robust than ever and includes a wide variety of mechanisms of actions and options for patients.

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Over the past decade the prevalence of obesity as defined by a body mass index (BMI) ≥ 30 kg/m2 has significantly increased. In the U.S. more than 78 million adults are estimated to be obese.1 The World Health Organization projects that by 2025 up to half the U.S. population will be obese. Cardiovascular disease (CVD) and diabetes mellitus (DM) are the main comorbid conditions that are complicated by obesity. Initial weight loss of 5% to 10% of total body weight reduces CVD risk factors, prevents or delays the development of type 2 DM (T2DM) and improves the health consequences of obesity.2

To date, public health initiatives that have focused on obesity prevention and lifestyle intervention have had marginal success. In recent years, anti-obesity drug therapies have had a limited role in clinical treatment algorithms. In 2013, the American Medical Association acknowledged obesity as a disease. In turn, this acknowledgement allowed the recognition of anti-obesity drugs as acceptable therapeutic adjuncts to intensive lifestyle intervention that could address the growing obesity endemic.

In the past, medications for weight reduction were limited. Several that were FDA approved had to be removed from the market due to safety concerns. With few approved options, clinicians often had to resort to off-label use of medications. However, the landscape has changed with 4 new medications gaining recent FDA approval. This review covers older available medications and the newer medications that are now available.

Sympathomimetics

Sympathomimetic drugs have been approved for use as a pharmacological method to lose weight since 1960. Of the many versions of this drug class that have been available since then, there are 4 major versions available today. These include diethylpropion3 and benzphetamine,4 both approved in 1960; phendimetrazine, approved in 1976;5 phentermine, approved in 1980;6 and phentermine hydrochloride, approved in 2012.7 Despite the existence of several other classes of drugs to treat obesity, phentermine remains the most often prescribed weight loss drug in the U.S.8

Although the mechanism of action (MOA) of sympathomimetic drugs is not particularly clear, weight loss from these medications is believed to be due to the increase in the release of biogenic amines (mainly norepinephrine, but also possibly dopamine), from storage sites in nerve terminals. It is possible that these drugs slow catecholamine metabolism by inhibiting the actions of monoamine oxidase. The resulting increase in amine availability, particularly in the lateral hypothalamic feeding center, is associated with reduced food intake. Interestingly, injection of these drugs into the ventromedial satiety center dooes not seem to suppress food intake, and the effects of biogenic amines on increasing metabolism does not seem to play a significant role in weight loss in patients on these medications.9

Each of these drugs is rapidly absorbed from the gastrointestinal (GI) tract except for phentermine hydrochloride, the newest of the medications in this class. Phentermine hydrochloride is a sublingual tablet that is readily absorbed through the buccal mucosa.5 All of the drugs in this class are excreted through the kidneys, with varying rates. Each drug’s excretion is highly dependent on the pH of the urine—more alkaline conditions result in less excretion and more acidic conditions result in more excretion. As a result, these drugs should be used with caution in patients with renal impairment; however, there are no specific contraindications listed for patients with poor renal function.

The adverse effects (AEs) for this drug class are to be expected from an increase in the release of biogenic amines in the central nervous system (CNS). The most common AEs include palpitations, tremors, restlessness, insomnia, dry mouth, constipation, diaphoresis, changes in libido, and irritability. The more dangerous AEs that have been observed include arrhythmias, hypertension, dependency/abuse, convulsions, acute transient ischemic colitis, and acute urinary retention secondary to increased bladder sphincter tone, transient hyperthyroxemia, and paranoia.10

Several contraindications exist for sympathomimetics, including the presence of advanced arteriosclerosis, symptomatic CVD, moderate to severe hypertension, hyperthyroidism, glaucoma, patients in an agitated state, or those with a history of amphetamine abuse. The warnings for prescribers include pulmonary hypertension and cardiomyopathy secondary to chronic use of sympathomimetics, and valvular heart disease secondary to use of sympathomimetics with additional anorectic agents.

Additional precautions should be considered in those with a history of anxiety/psychosis, those who operate machinery and motor vehicles, and even those with mild hypertension. The data surrounding the effects of sympathomimetics on blood pressure (BP) appears to be conflicting and the relationship does not seem to have been significantly studied in depth to warrant any definitive conclusions. The MOA of this drug class itself is enough to urge caution to prescribers.11 Special attention should be given to patients with diabetes when using sympathomimetics. A reduction of insulin dose or oral hypoglycemic dose may be necessary in some people with diabetes.

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