US Pharm. 2014;39(2):51-54.
ABSTRACT: Metabolic syndrome comprises many risk factors,
including—but not limited to—high blood sugar, hypertension, and
dyslipidemia, the incidences of which are continuing to rise in the
United States. It is important for pharmacists to be familiar with the
various components of metabolic syndrome so that they can perform
appropriate screenings in at-risk patients and encourage therapeutic
lifestyle changes. Pharmacists can also make drug-therapy
recommendations to help prevent further complications associated with
Metabolic syndrome is a collection of co-occurring disorders
that increase the risk of heart disease, stroke, and diabetes mellitus
(DM). Metabolic risk factors such as elevated plasma glucose, high blood
pressure (BP), and dyslipidemia contribute to atherosclerosis, as well
as to a prothrombotic and proinflammatory state.1,2
Additional risk factors include abdominal obesity, physical inactivity,
insulin resistance, cigarette smoking, and family history of premature
coronary heart disease (CHD).2 Compared with patients who do
not have metabolic syndrome, those with metabolic syndrome are twice as
likely to develop CHD and five times more likely to develop DM.1-3
While the pathophysiology of metabolic syndrome is multifactorial, one
component is the proinflammatory state, as denoted by an elevated level
of C-reactive protein. In obesity, cytokine release from the adipose
tissue causes inflammation, which leads to the development of
dyslipidemia and increasing waist circumference.2,4
In the United States, metabolic syndrome affects approximately 35% of adults, of whom 85% also have DM.2,3
Prevalence, which varies by sex with respect to race and ethnicity,
increases with age. Compared with non-Hispanic white males, non-Hispanic
black males have a lower incidence of metabolic syndrome (37% vs. 25%).
Non-Hispanic black and Mexican-American females are nearly 1.5 times
more likely than non-Hispanic white females to have metabolic syndrome.5
Forty-one percent of males and 37% of females aged 40 to 59 years and
52% of males and 54% of females older than 60 years meet diagnostic
criteria for metabolic syndrome.5
Diagnosis and Treatment
The National Cholesterol Education Program (NCEP) Adult Treatment
Panel III (ATP III) outlines diagnostic criteria for metabolic syndrome (TABLE 1).6
Treatment for metabolic syndrome focuses on modification of these
criteria. The primary treatment approach is nonpharmacologic, including
weight reduction, dietary changes, physical activity, and smoking
cessation.6 In addition to therapeutic lifestyle changes (TLC), patients may consider adjunct treatment with a weight-loss agent.
Medications such as Xenical or Alli (orlistat) or one of two recently
approved weight-loss agents, Belviq (lorcaserin) and Qsymia
(phentermine-topiramate extended-release), may be used adjunctively to
manage weight loss. TABLE 2 presents these agents in greater detail.
Orlistat: Xenical and Alli are indicated for weight
loss and maintenance in obese patients and to reduce the risk of weight
gain following a substantial weight loss. Orlistat exerts its effect on
weight as a reversible inhibitor of gastrointestinal (GI) lipase
enzymes. Since this drug acts locally within the GI tract, common side
effects are GI in nature.7
Lorcaserin: Belviq is indicated as adjunct
treatment in obese or overweight patients with comorbid conditions
including hypertension, dyslipidemia, and type 2 DM (DM2). The CDC
defines obesity as a BMI of ≥30.0 kg/m2 and overweight as a BMI of 25.0 to 29.9 kg/m2.
Lorcaserin, an agonist of the serotonin 2C receptor, promotes satiety
and decreases food consumption. Dosing is 10 mg twice daily. Side
effects are minimal; however, patients with DM are more susceptible to
hypoglycemia. If ≥5% weight loss is not achieved after 12 weeks, therapy
should be discontinued. Lorcaserin is a Class IV controlled substance
because of its potential for abuse. Patients should be advised to take
this drug only as prescribed and never to share it.8
Three phase III clinical trials (BLOOM, BLOOM-DM, and BLOSSOM)
investigated the safety and efficacy of lorcaserin in nondiabetic and
diabetic subjects.9-11 The primary outcome was the percentage
of subjects achieving ≥5% weight loss from baseline to week 52. In
BLOOM, lorcaserin 10 mg twice daily was compared with placebo twice
daily. The primary outcome was achieved in 47.5% of the lorcaserin group
and 20.3% of the placebo group, respectively (P <.0001).9
BLOOM-DM compared both of these treatment modalities, plus lorcaserin
10 mg once daily. The once-daily group also received a placebo dose
nightly for blinding purposes. The primary outcome was achieved in
37.5%, 44.7%, and 16.1% of the lorcaserin twice-daily, lorcaserin
once-daily, and placebo groups, respectively (P <.001).10
BLOSSOM evaluated the same treatment modalities as BLOOM-DM. Higher
percentages of subjects in the lorcaserin twice-daily (47.2%) and
once-daily (40.2%) groups met the primary outcome, versus 25% of the
placebo group (P <.0001).11
Phentermine/Topiramate Extended-Release: Although the
exact mechanism of action of Qsymia is unknown, its components—a
sympathomimetic and an extended-release antiepileptic—are thought to
augment chronic weight management by increasing satiety and decreasing
appetite. The indications are the same as those for lorcaserin. Dose
titration is required upon initiation and discontinuation to prevent
seizure occurrence. Dosing is 3.75/23 mg daily for 14 days, then 7.5/46
mg daily as maintenance. If 3% weight loss is not achieved after 12
weeks, therapy may be discontinued, or the dosage may be deescalated or
increased to 11.25/69 mg daily for 14 days before being increased to a
maximum of 15/92 mg daily. If 5% weight loss is not achieved after 12
weeks on the maximum dosage, therapy should be gradually discontinued.
This product is available only through pharmacies enrolled in the Qsymia
Certified Pharmacy Network.12
The safety and efficacy of phentermine/topiramate extended-release
were evaluated in three phase III clinical trials (EQUIP, CONQUER, and
SEQUEL).13-15 Over 52 weeks, EQUIP assessed severely obese subjects (BMI ≥35 kg/m2) and CONQUER studied overweight and obese subjects (BMI ≥27 to ≤45 kg/m2)
with two or more comorbidities, such as hypertension, hyperlipidemia,
DM, or increased waist circumference (women, ≥88 cm; men, ≥102 cm). The
endpoint was ≥5% weight loss by trial completion. In EQUIP, subjects
taking 3.75/23 mg and those taking 15/92 mg achieved an overall weight
loss of 5.1% and 10.9%, respectively, versus 1.6% for the placebo group (P
<.0001). In CONQUER, subjects taking 7.5/46 mg and those taking
15/92 mg achieved an overall loss of 7.8% and 9.8%, respectively, versus
an overall loss of 1.2% in the placebo group (P <.0001).13,14
SEQUEL, a 52-week CONQUER extension study, evaluated long-term results
of drug therapy, focusing on weight-loss maintenance during year 2. From
baseline, 9.3% and 10.5% of subjects taking 7.5/36 mg and 15/92 mg,
respectively, experienced weight-loss maintenance (P <.001).15
Management of Other Risk Factors
In addition to weight loss and/or maintenance, the other components
of metabolic syndrome must be managed. In treating dyslipidemia, the
primary goal is to lower LDL cholesterol (LDL-C). The target LDL-C
depends upon the presence of CHD, risk equivalents, or risk factors. The
ATP III LDL-C goal—as well as optional goals described in the 2004
update to the NCEP’s clinical practice guidelines—for each risk category
appears in TABLE 3.6,16 To achieve goal LDL-C,
TLC—a multifaceted lifestyle approach—must be implemented. In addition,
drug therapy may be required to achieve the desired LDL-C. An HMG-CoA
(statin) is recommended, not only for its LDL-C reduction potential, but
also for its primary prevention of cardiovascular disease in high-risk
patients and secondary prevention in patients with CHD.6
According to the Seventh Report of the Joint National Committee on
Prevention, Detection, Evaluation, and Treatment of High Blood Pressure
(JNC 7), a number of TLC are warranted for BP reduction. These include
the Dietary Approaches to Stop Hypertension (DASH) eating plan
(emphasizing consumption of fruits, vegetables, fat-free or low-fat
milk/dairy products, and whole grains); sodium restriction (≤2.4 g/day);
weight reduction (to maintain BMI of 18.5-24.9 kg/m2);
physical activity (regular aerobic activity for 30 minutes/day most days
of week); moderate alcohol consumption (men, ≤2 drinks/day; women, ≤1
drink/day); and smoking cessation.17
The JNC 7’s target BP goal for patients with chronic kidney disease
or DM is <130/80 mmHg; for all others, it is <140/90 mmHg.17
The American Heart Association provides hypertension guidelines and
goals for other categories. Target BP for patients with coronary artery
disease (CAD) or CAD risk equivalents (carotid artery disease,
peripheral artery disease, abdominal aortic aneurysm), as well as those
at high risk for CAD (DM, chronic renal disease, or 10-year Framingham
risk score ≥10%), is <130/80 mmHg. For ventricular dysfunction, the
target BP goal is <120/80 mmHg.18 According to the JNC 7, drug-therapy selection is based upon compelling indications (TABLE 4).17
The 2013 American Diabetes Association guidelines recommend lifestyle
modifications (similar to those in JNC 7) to reduce blood glucose (BG)
and prevent DM2. Metformin also may be considered to treat elevated BG.
Without a diagnosis of DM, the fasting BG goal is <100 mg/dL.19
Finally, since a proinflammatory state exists in metabolic syndrome,
the use of aspirin should be considered. Aspirin 81 mg daily should be
considered in patients with a 10-year risk ≥10%. Aspirin 81 to 325 mg
daily should be used for secondary prevention in patients with a history
Since most components of metabolic syndrome do not have associated
symptoms, patients may not be concerned about risk. Pharmacists can host
educational and screening programs to foster awareness of metabolic
syndrome and identify at-risk patients who are candidates for therapy.
Upon identification, patients should schedule a primary care appointment
for further assessment and pharmacologic therapy.
Pharmacists can intervene further by setting measurable and
achievable goals; assessing adherence; identifying barriers to
treatment; emphasizing the role of nonpharmacologic therapy; supporting
patients engaged in lifestyle modifications; and educating patients
about safe medication use, risk-factor modification, diagnosis of
metabolic syndrome, device use (glucometer or BP cuff), and lifestyle
interventions. Pharmacists are in an ideal position to assess patients’
self-monitoring of weight, BG, and BP and help them develop care plans.
As another component of the medication-therapy process, pharmacists can
help patients develop and update a personal medication record.20 No matter which aspect is addressed, it is essential to engage patients during all encounters.
NOTE: Subsequent to the writing of this paper, new guidelines were
issued by the Eighth Joint National Committee (2014), American Diabetes
Association (2014), American College of Cardiology/American Heart
Association (ACC/AHA) Task Force on Practice Guidelines [cholesterol
treatment] (2013), and ACC/AHA/The Obesity Society [overweight/obesity
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