Screening and Prevention of Complications
Periodic health screening with a measurement of both height and weight to calculate BMI is recommended by many organizations including the National Heart, Lung, and Blood Institute (NHLBI), the US Preventive Services Task Force, and the WHO. Furthermore, the NHLBI also recommends waist circumference measurement routinely to find persons at risk of metabolic complications of overweight. Patients who are found to be in the overweight or obese categories of BMI are recommended to have other risk factors checked as well, including blood pressure, fasting glucose, and lipoprotein levels.
Therapeutic Approaches for Weight Loss
Several behavioral, pharmacologic, and surgical therapies for weight loss have been studied in randomized controlled trials. In general, behavioral interventions with lifestyle change including diet and exercise and pharmacologic therapies work to achieve modest amounts of weight loss while patients adhere to the intervention. Recommended for more severe levels of obesity, bariatric surgery does lead to larger amounts of weight loss, but requires lifelong medical supervision and management of the side effects associated with the surgery.
Behavior, Diet, and Exercise Therapies
While many believe that long-term weight loss with lifestyle change is not achievable by most patients, longitudinal studies have found that 20% of overweight individuals are successful at weight loss defined as losing at least 10% of initial body weight and maintaining the loss for at least 1 year. Individuals enrolled in the National Weight Control Registry have lost an average of 33 kg and maintained the loss for more than 5 years. Behaviors that have been most effective for long-term weight loss include high levels of physical activity (∼1 hour/day), self-monitoring weight, eating a low-calorie, low-fat diet, eating breakfast regularly, and maintaining a consistent eating pattern throughout the week.
Several commercial, fad, and therapeutic dietary interventions exist for weight loss. Recent dietary trends have focused on relative changes in macronutrient composition of the diet to achieve weight loss, such as low-fat or low-carbohydrate diets. Few have been rigorously tested, and no trials have long-term outcome data (defined as the occurrence of comorbidities or mortality). A recent randomized trial comparing four popular diets (Atkins, Zone, Weight Watchers, and Ornish diet) found that weight change did not significantly differ between participants assigned to any of the four diets, and better dietary adherence predicted higher amount of weight loss. The most difficult diets for participants to adhere to were the very low-fat diet (Ornish) and the low-carbohydrate diet (Atkins). In a recent meta-analysis of five dietary trials for weight loss, low-carbohydrate non–energy-restricted diets were found to be as effective as low-fat, energy-restricted diets for weight loss up to 1 year. The weighted mean difference in weight loss was greater in the low-carbohydrate diets (−3.3 kg, 95% CI −5.3 to −1.4 kg, p = 0.02) in the first 6 months, but there was no difference in weight loss after 12 months between the two types of diet (−1.0 kg, 95% CI −3.5 to 1.5 kg, p = 0.15). Additionally, there was no clear benefit on cardiovascular risk factors with either type of diet.
Physical Activity Interventions.
The Institute of Medicine recommends physical activity of 60 min/d for most days of the week for weight loss and/or control of weight. The recommendations for heart disease prevention are 30 min/d of moderate-intensity physical activity on most days per week, or at least 150 min/wk.
In a systematic review of trials of an aerobic physical activity intervention in overweight populations, body weight decreased significantly in seven of nine trials, but weight increased in two trials. The two studies that combined diet with aerobic training had the largest amounts of weight loss (>10 kg each). However, these trials were uncontrolled and of relatively short duration. It remains unclear whether long-term lifestyle change with physical activity can decrease risk of cardiovascular disease or mortality in obese individuals.
Weight loss medications have had mixed results with most delivering modest amounts of short-term weight loss, often associated with many undesirable side effects. Currently there are four main categories of weight loss medications approved by the FDA: adrenergic agents, serotonergic agents, combination of both adrenergic/serotonergic agents, and lipase inhibitors. Other medications available for off-label use include some antidepressants and anticonvulsant agents. A majority of available obesity treatments work by suppressing appetite centrally. One approved medication, orlistat, prevents digestion and absorption of dietary fat by inhibiting the gut enzyme lipase. There are several different sites of action under investigation for potential medications including specific neurotransmitter targets to decrease appetite and/or promote satiety, endocannabinoid system antagonists and opioid receptor targets to reduce food intake, and peripheral targets that work at the level of the intestines or pancreas to modulate food intake.
Table 20–5 shows specific medications in each category, the amount of weight loss reported in trials compared to placebo from a recent review and meta-analysis, and the common side effects of each agent. The two most frequently studied weight loss medications, sibutramine and orlistat, have had the best efficacy in longer- term trials (52 weeks). However, both of these drugs are associated with significant side effects which limit their use. Other antiobesity medications in the drug development pipeline include lorcaserin, an agonist that targets serotonin 2C receptors to cause satiety, and a multiple monoamine reuptake inhibitor, tesofensine, that reduces reuptake of norepinephrine, serotonin, and dopamine to cause appetite suppression. An endocannabinoid receptor antagonist, rimonabant, was successful in producing modest weight loss and improving metabolic complications. However, adverse central nervous system side effects of rimonabant including depression and anxiety precluded introduction of this drug into clinical practice.
Table 20–5 Medications for Treatment of Obesity. ||Download (.pdf)
Table 20–5 Medications for Treatment of Obesity.
|Drug||Category||Recommended Dose||Mean Weight Loss vs Placebo (Range in kg)||Side Effects|
|Phentermine||Adrenergic agent||15-37.5 mg daily||3.6 kg (0.6-6.0 kg)||Dry mouth, headache, insomnia, irritability, tachycardia, ↑BP|
|Diethylpropion||Adrenergic agent||3.0 kg (−1.6 to 11.5 kg)||Central nervous system stimulation, dizziness, headaches, insomnia, palpitations, tachycardia, mild ↑BP|
|Orlistat||Lipase inhibitor||60-120 mg 3 times daily||2.89 kg (2.27-3.51 kg)||Diarrhea, flatulence, fecal urgency and incontinence, abdominal pain, dyspepsia|
|Sibutramine||Norepinephrine/serotonin reuptake inhibitor||10-15 mg daily||4.45 kg (3.62-5.29 kg)||Dry mouth, insomnia, constipation, tachycardia, ↑BP|
|Off-Label Drugs Associated with Weight Loss|
|Buproprion||Antidepressant||300-400 mg daily||2.77 kg (1.1-4.5 kg)||Dry mouth, insomnia, diarrhea, constipation|
|Fluoxetine||Selective serotonin reuptake inhibitor||60 mg daily||0.90-9.1 kg||Nervousness, sweating, tremors, nausea, vomiting, fatigue, somnolence or insomnia, diarrhea|
|Topiramate||Anticonvulsant||96 mg/d or 192 mg/d||6.5% more than placebo (4.8%-8.3%)||Paresthesias, difficulty with concentration, change in taste, dizziness, fatigue|
|Zonisamide||Anticonvulsant||100-600 mg daily||5% decrease compared to placebo||Dizziness, confusion, difficulty with concentration|
Complementary and alternative medications such as herbs, vitamins, nutritional supplements, and meal replacement therapies are commonly used by the general public for weight loss. However the efficacy and safety of these herbal remedies has not been well studied. A recent meta-analysis of trials found that compounds containing ephedra, Cissus quadrangularis, ginseng, bitter melon, and zingiber had some short-term efficacy with weight loss with mostly mild adverse effects. However, longer-term randomized controlled trials are needed to prove efficacy and safety.
Surgical treatment for weight loss has been performed for the past 50 years, and these procedures are increasing in popularity. Approximately 20,000 weight-loss surgeries were performed in 1995 and over 140,000 were done in 2004, a sevenfold increase. There are three main types of bariatric surgeries: restrictive, malabsorptive, and those that have both a restrictive and a malabsorptive component. Purely restrictive surgeries include horizontal gastroplasty, vertical banded gastroplasty, silastic ring vertical gastroplasty, and adjustable gastric banding. Purely malabsorptive surgeries include the oldest of all bariatric procedures, the jejunoileal bypass, biliopancreatic diversion, duodenal switch, and long limb gastric bypass. The combination of restrictive and malabsorptive surgical procedure is the most commonly used bariatric surgery worldwide, the Roux-en-Y gastric bypass procedure (RYGB), which involved stapling the upper stomach into a small 30-mL pouch and attaching it to the jejunum bypassing the lower stomach and duodenum. This procedure can be done with an open surgical approach, or now more commonly with a laparoscopic approach.
Several studies have examined the effects of different types of bariatric surgeries on various outcomes including weight loss, comorbid disease, complication rates, and mortality. There are very few randomized controlled trials comparing different surgical procedures, so most of the outcomes data come from case series, prospective cohort analyses, or nonrandomized trials. The largest and longest double cohort study to date is the Swedish Obese Subjects (SOS) study in which obese adults who voluntarily underwent bariatric surgery were matched to a control group of medically treated patients. After 10 years of follow-up of 1703 participants, those treated with surgery had a 16% weight loss compared to 2% in the controls (p <0.001). They compared the different types of bariatric surgery approaches in this study and found that those who had gastric bypass lost more weight than those who received banding procedures or the vertical banded gastroplasty.
An earlier meta-analysis determined the effect of bariatric surgery on weight loss, mortality, and four comorbid diseases including diabetes, hyperlipidemia, hypertension, and sleep apnea. The mean excess weight loss was 61.2% (58.1%-64.4%), highest in those who had the biliopancreatic diversion or duodenal switch (70.1%) and lowest in those who underwent gastric banding (47.5%). Operative mortality within 30 days of the surgery was 0.1% for purely restrictive procedures and 0.5% for gastric bypass, and 1.1% for biliopancreatic diversion or duodenal switch procedures. Type 2 diabetes resolved in approximately 77% of patients after surgery, hyperlipidemia improved in 70%, hypertension resolved in 62%, and obstructive sleep apnea resolved in 86%.
Much attention has focused on determining the mechanisms involved in the dramatic weight loss associated with bariatric surgery. Previous hypotheses that restrictive procedures reduce the quantity of food ingested at any one time, malabsorptive procedures cause wasting of fat calories, with RYGB employing a combination of both mechanisms, have not been supported by studies. More recent thinking attributes weight loss after bariatric procedures to a substantial decline in hunger and increase in satiety that is regulated through neuroendocrine mechanisms and gut hormones such as ghrelin and PYY. The effect of RYGB surgery on ghrelin levels is controversial since some studies have found increased levels, no change, or decreased levels after surgery. These inconsistent results may be explained by the timing of ghrelin sampling after surgery. After purely restrictive surgeries, ghrelin levels increase, which may help explain the more dramatic weight loss observed following RYGB vs purely restrictive surgeries. PYY levels rise to those of a nonobese person following vertical banded gastroplasty. However, with RYGB, there is an early exaggerated response in PYY secretion, approximately two- to fourfold greater than that observed in lean, obese, or gastric banded patients, which may contribute to the sustained weight loss seen with this type of procedure.
Defining appropriate patient criteria to minimize risks and maximize the benefits from bariatric surgery have been debated. Some studies have concluded that surgical intervention is more effective for weight loss and control of comorbid diseases than nonsurgical treatments in patients with a BMI ≥40 kg/m2. In 2004, with extensive scientific input, the National Coverage Advisory Committee panel concluded that bariatric surgery could be offered to Medicare beneficiaries with BMI ≥35 kg/m2 who have at least one comorbid disease associated with obesity and have been unsuccessful previously with medical treatment of obesity. Other criteria for patient selection proposed by leading associations include adequate patient commitment with medical follow-up and use of dietary supplements, no other reversible endocrine disorders causing obesity, no current substance abuse, and no severe psychiatric illness.
Interventions with Efficacy in Children
Several studies have investigated behavioral and lifestyle intervention programs for pediatric weight loss. Most randomized controlled trials of overweight children and adolescents have found positive, but small- to -moderate effects, of combined lifestyle interventions on BMI. Family-based behavioral weight loss programs have produced larger effects that persist for several months of follow-up. Less is known about the long-term safety and efficacy of pharmacologic agents for treatment of pediatric obesity.