Kathleen M. McTigue, M.D.a; Russell Harris, M.D., M.P.H.b; Brian Hemphill, M.D.c; Linda Lux, M.P.A.d; Sonya Sutton, B.S.P.H.e; Audrina J. Bunton, B.A.f; Kathleen N. Lohr, Ph.D.g
The authors of this article are responsible for its contents, including any clinical or treatment recommendations. No statement in this article should be construed as an official position of the Agency for Healthcare Research and Quality or the U.S. Department of Health and Human Services.
Address correspondence to: Russell Harris, M.D., M.P.H.; Cecil G. Sheps Center for Health Services Research; CB No. 7590; 725 Airport Road; Chapel Hill, NC 27516; Phone: (919) 966-2949; E-mail: rharris@med.unc.edu
Select for copyright information. The USPSTF recommendation based on this review are online.
The summaries of the evidence briefly present evidence of effectiveness for preventive health services used in primary care clinical settings, including screening tests, counseling, and chemoprevention. They summarize the more detailed Systematic Evidence Reviews, which are used by the U.S. Preventive Services Task Force (USPSTF) to make recommendations.
Abstract
Background
Methods
Results
Discussion
Acknowledgments
References
Notes
Background. Obesity poses a considerable and growing health burden. We examined evidence for screening and treating obesity in adults.
Data Sources. MEDLINE® and Cochrane Library (January 1994 through February 2003).
Study Selection. Systematic reviews, randomized controlled trials, and observational studies of obesity's health outcomes or treatment efficacy.
Data Extraction. Two reviewers independently abstracted data on study design, population, sample size, treatment, outcomes, and quality.
Data Synthesis. No trials evaluated obesity mass screening, so we evaluated indirect evidence for efficacy. Pharmacotherapy or counseling interventions produced modest (generally 3-5 kg) weight loss over at least 6 (pharmacotherapy) or 12 (counseling) months. Counseling was most effective when intensive and combined with behavioral therapy. Maintenance strategies helped retain weight loss. Selected surgical patients lost substantial weight (10-159 kg over 1-5 years). Weight reduction improved blood pressure, lipids, and glucose metabolism and decreased diabetes incidence. Treatment trials' internal validity was fair-to-good, and external validity was limited by the minimal ethnic or gender diversity of volunteer participants. No data evaluated counseling harms. Primary adverse drug effects included hypertension with sibutramine (mean increase: 0.0-3.5 mm Hg) and gastrointestinal distress with orlistat (1-37 percent of patients). Under 1 percent (pooled samples) of surgical patients died; up to 25 percent needed surgery again over 5 years.
Conclusions. Counseling and pharmacotherapy can promote modest sustained weight loss, improving clinical outcomes. Pharmacotherapy appears safe in the short term; long-term safety is less established. In selected patients, surgery promotes large amounts of weight loss with rare but sometimes severe complications.
Obesity is an increasingly significant U.S. health problem. Over 4 decades, the prevalence of obesity (body mass index [BMI], kilograms of weight divided by height in meters squared [kg/m2], > 30) has increased from 13 percent to 31 percent in adults and the prevalence of overweight (BMI 25-29.9 kg/m2) has increased from 31 percent to 34 percent.1 Concurrent increases occurred in adolescents and children.2-4 Obesity is especially common in African Americans, some Hispanic populations, and Native Americans, and some health sequelae reflect similar ethnic differences.5,6 Obesity is more common in women, and overweight is more common in men.5 Obesity is a risk factor for major causes of death, including cardiovascular disease, numerous cancers, and diabetes,7 and is linked with markedly diminished life expectancy.8,9 Osteoarthritis, gall bladder disease, sleep apnea, respiratory impairment, diminished mobility, and social stigmatization are associated with obesity.10
Health risk is better established for obese persons than for overweight persons. However, overweight status also carries risk11; even mild-to-moderate overweight in young adults predicts subsequent obesity,12 and weight gain is associated with adverse outcomes.13 Visceral fat versus subcutaneous fat is particularly linked with adverse cardiovascular profiles in diverse ethnic and racial groups.14-20 Body composition varies with race and ethnicity; (e.g., Asians may be more likely21 and African Americans less likely to accumulate visceral fat than whites15,22,23); health implications may also vary.14-20
Estimated direct obesity costs are 5.7 percent of total U.S. health expenditures.24 Expected lifetime costs for cardiovascular disease and its risk factors increase by 20 percent with mild obesity, by 50 percent with moderate obesity, and by nearly 200 percent with severe obesity.25
We reviewed the medical literature for effectiveness of adult obesity screening—the conscious measurement of weight status to clinically address body weight—and treatment. Although obesity may seem obvious, only 42 percent of obese U.S. adults report receiving health care advice to lose weight.26
In 1996, the U.S. Preventive Services Task Force (USPSTF) recommended periodic height and weight measurement.7 Increased obesity prevalence, therapeutic changes, and accumulating evidence of associated health risk necessitate an update. The Research Triangle Institute (RTI)-University of North Carolina Evidence-based Practice Center developed a systematic review of evidence to assist the USPSTF in this process.
We developed an analytic framework of obesity screening components, with key questions, and eligibility criteria (Appendix Table 1). Randomized controlled trials (RCTs) or systematic reviews of RCTs were preferred evidence: when lacking, we evaluated cohort and nonrandomized controlled studies. Because of limited long-term data, we accepted pharmacotherapy efficacy trials with 6 months minimum followup; otherwise, we required at least 12 months. Study quality was rated using USPSTF criteria (Appendix Table 2).27
We examined the USPSTF's 1996 review,7 then searched MEDLINE® and the Cochrane Library for articles published in English between January 1994 and February 2003.27 We evaluated well-done systematic reviews from the National Institutes of Health (NIH),11 the Canadian Task Force on Preventive Health Care (CTFPHC),28 the University of York for the U.K. National Health Service (NHS),29 the National Task Force on the Prevention and Treatment of Obesity,30 and the British Medical Journal's Clinical Evidence.31 We used the last as the sole systematic review source for drug efficacy as the comprehensive reviews were outdated.
To compare treatment efficacy across reviews, we extracted data from each reviews evidence tables on studies with current interventions and at least 1-year followup. We also drew from their general conclusions. We then reviewed primary literature not covered by prior reviews. At least 2 authors independently reviewed abstracts and articles, excluding those not meeting eligibility criteria, then abstracting eligible articles. We abstracted or calculated 95 percent confidence intervals (CIs) for treatment efficacy from available data whenever possible. When sample size was not reported with variance,32,33 baseline sample was used.
The U.S. Agency for Healthcare Research and Quality (AHRQ) funded this research. Agency staff and USPSTF members participated in the initial study design and reviewed interim analyses and the final manuscript.
Although no RCTs evaluated obesity screening efficacy, we found studies that address obesity's health risks, treatment efficacy, and weight loss' health implications.
Longitudinal data showed J-shaped or U-shaped relationships between absolute mortality and BMI34-45; elevated risk at low BMI may partly reflect smoking,35,37,42 or BMI's limitations in approximating fat mass (46). BMI of lowest mortality risk varied, but was generally within the normal range for men and the normal-to-overweight range for women.34-45 Morbidity risk increased fairly linearly with BMI. Risk was strongest for cardiovascular disorders.37,43,47 Breast, colon, uterine, and ovarian cancer incidence increased with BMI. 44,48
In the United States, the association between excess body weight and mortality may be weaker for African Americans than for whites.41,42,49 However, race-specific data are rare, and sample size concerns limit conclusions. Mortality risk from excess weight may lessen with age; health risks from obesity are unclear beyond age 74.50
BMI, the most common screening test for obesity, is easy to measure, highly reliable, and closely correlated (0.7-0.8) with adult body fat.7,51,52 Validity may vary by population characteristics, including ethnicity53-55 and possibly age.51,56 Clinical relevance is established by prospective links with diverse health outcomes.37,40-43,47,57
Waist circumference and the waist-to-hip ratio may capture the increased cardiovascular risk for central adiposity—even among non-obese persons.44,58-61 Of these, waist circumference more closely approximates visceral adiposity, particularly in African Americans.15,20 Skinfold thickness measurement requires training for accuracy, so was judged undesirable.7 We focused on BMI because BMI is linked with the broadest range of health outcomes, entry criteria for most treatment studies are BMI-based, and such trials typically report weight or BMI change.
Counseling aims to promote change in diet and/or exercise; behavioral interventions are strategies to help patients acquire the skills, motivations, and support to change diet and exercise patterns. For comparison with other treatments, we consider counseling for diet, exercise, or some combination, potentially with behavioral theory, in aggregate. Importantly, each counseling component includes diverse options, possibly in combination. Also, while primary-care-based physical activity counseling has uncertain efficacy,62 physical activity has diverse health benefits63 and obesity's cardiovascular risk may be reduced by fitness.64 Prior systematic reviews found modest counseling and behavioral intervention effects, while more recent RCTs showed consistent findings (Table 1).
In 29 trials with at least 1-year followup, the NIH review found average weight change in diet and/or physical activity groups (some including behavioral therapy) of 1.9 to -8.8 kg (mean, -3.3 kg) corrected for change in controls (Table 1).11 Counseling for low-calorie diets (1,000-1,200 kilocalories [kcal] per day) reduced body weight by an average 8 percent over 3 to 12 months and decreased abdominal fat. Although very-low-calorie diets produced greater initial weight loss than low-calorie diets, results were similar beyond 1 year. Counseling for physical activity (24 RCTs) led to 2 percent to 3 percent loss of weight and reduced abdominal fat. Combined diet and physical activity counseling produced greater reduction of weight and abdominal fat than either approach alone. Behavior therapy was a useful adjunct to diet and/or physical activity counseling. Longer-term efficacy depended on continued intervention.
The U.K. NHS review found that behavioral interventions, combined with diet or exercise, appeared effective and long-term maintenance strategies useful.29 In 24 studies, mean net weight change (intervention arms corrected for controls) was -3 kg over 12 to 60 months (Table 1). The CTFPHC review found weight reduction was most effective during supervised dietary treatment, with subsequent gradual weight regain.28 In 6 trials, net weight change was -0.2 to -4.5 kg after 24 to 84 months.
We identified 17 additional counseling RCTs.65-82 We examined weight loss and loss maintenance trials separately.67,73 Limitations included loss to followup (5-38 percent) and differential attrition between treatments. External validity concerns included volunteer enrollment versus random community sampling and poor gender and ethnic diversity.
To compare diverse programs (Appendix Table 3), we assessed intervention mode (group or individual), components (diet, exercise, behavioral), and intensity (low, moderate, high). Intensity was rated by frequency of person-to-person contact in the first 3 months. Moderate intensity was defined as monthly contact, high intensity was defined as more frequent contact, and low intensity was defined as less frequent contact.
As shown in Figure 1 (PDF File, 92 KB; PDF Help) (a summary of trials for which the difference in mean weight change between intervention and control groups could be calculated, as close as possible to 1-year followup), high-intensity trials were most likely to be successful, generally achieving 3 to 5 kg of weight loss. Two intensive trials reported success frequency. In 1 trial,67 mean weight loss due to intervention was 3.4 kg (CI, 2.6-4.2); 30 percent more persons in the treatment group than in the control group lost at least 5 percent of their body weight, in the other, a net 5.5 kg loss (P < 0.001) corresponded with 38 percent in the intervention group losing 7 percent total body weight.81
Because not all trials used a null control (many compared one counseling intervention with another), our treatment efficacy estimates (intervention effect minus control) may be conservative. Of 11 high-intensity interventions to promote weight loss, 6 used a true control; 4 were successful (2.5-5.5 kg loss beyond controls in 12-54 months),66,67,70,81 and 2 showed borderline76 or transient69 weight reduction (Table 2). In 5 trials, 1 high-intensity intervention led to more weight loss than another.65,72,74,78,82 Moderate-intensity interventions showed mixed results.71,79 Two of the 3 low-intensity weight loss interventions were ineffective.77,83
Successful interventions typically included 2 to 3 components (diet, exercise, and behavioral therapy). Only 1 trial65 examined a combination of counseling and pharmacotherapy. In this trial, adding lifestyle counseling to sibutramine therapy led to a mean weight reduction of 7.3 kg (CI, 1.6-13.0), and adding a low-calorie diet to counseling and sibutramine therapy led to a mean weight reduction of 12.8 kg (CI, 8.2-17.4).65
Twelve- to 18-month prolonged, followup was reported in 3 high-intensity weight loss studies,67,70,76 2 of which included long-term maintenance strategies.66,76 Although participants regained weight, modest net loss (> 2 kg) was maintained for 24 to 36 months in 3 of 4 interventions.67,70,76
Trials designed to maintain weight loss showed some success.68,73 One promoted an additional 5-kg (1-year) loss.68 In another, weight-focused counseling promoted weight maintenance in 36 percent more participants than exercise-focused counseling.73
Overall, counseling promoted modest average weight loss (3-5 kg). Multi-component, intensive interventions including behavioral therapy most often led to weight loss. Maintenance strategies helped sustain loss.
Pharmacological obesity treatment has changed substantially in the past decade. Safety concerns have eliminated several options. Evidence of the efficacy of sibutramine (a dopamine, norepinephrine and serotonin re-uptake inhibitor) and orlistat (a gastrointestinal lipase inhibitor) evidence has increased. Both are approved for people with BMIs of 30 kg/m2 or more or people who have BMIs greater than 27 kg/m2 with other risk factors (e.g., hypertension, diabetes, or dyslipidemia) in combination with lifestyle change. Efficacy trials have also examined several drugs developed for non-weight-related purposes.
A recent obesity pharmacotherapy systematic review found that sibutramine promoted 2.8 to 4.2 kg of weight loss (7 RCTs) over 8 to 52 weeks in healthy adults and those with controlled hypertension, but weight regain followed treatment discontinuation.31 Orlistat's efficacy was similar (mean 3.5 kg loss in 10 RCTs of 1 to 2 years' duration). Phentermine (7.4 kg average loss in 1 RCT) and mazindol (3.8 kg average loss in 1 RCT, but no longer manufactured in the United States) caused modest weight loss in adults more than 15 percent overweight. Other small RCTs showed limited and inconsistent efficacy of diethylpropion (2 RCTs) or fluoxetine (2 RCTs).
We identified 18 additional RCTs meeting eligibility criteria: 7 evaluated sibutramine32,33,84-88; 8 evaluated orlistat89-96; 2 evaluated metformin81,97; and 1 evaluated multiple drugs.98 Three trials examined maintenance strategies.84,92,93 Attrition (3-50 percent) and poor adherence data were primary quality limitations. Generalizability issues were similar to the counseling trials.
In 6 weight loss trials (Figure 2; PDF File, 15 KB; PDF Help),32,33,85-88 sibutramine-treated participants lost 2.8 kg (CI, 1.6-4.0) to 7.8 kg (CI, 5.9-9.7) more than patients given a placebo (Table 3). Frequency of response, when recorded, was high; 27 percent (CI, 18-36) to 65 percent (CI, 60-70) of sibutramine-treated patients achieved 5-percent loss and 6 percent (CI, 1-10) to 34 percent (CI, 26-40) lost 10 percent.33,85-88 A 5-percent loss occurred in 19 percent (CI, 9-29) to 53 percent (CI, 36-70) more of drug-treated participants than control participants, and a 10-percent loss in 5 percent (CI, -1 to 10) to 27 percent (CI, 18-36) more.
In 6 trials,90,91-94,96 participants treated with a typical orlistat dose (120 mg 3 times daily) lost significantly more weight (2.8 kg [CI, 1.8- 3.7] to 4.5 kg [CI not calculable]) than did controls. In a sixth, not statistically significant trial, orlistat-treated participants lost 5.8 kg more than controls.95 In the 3 trials reporting response rates, 10 percent loss occurred in 14 percent (CI, 10-19) to 38 percent (CI, 29-47) of orlistat-treated participants, and such response occurred more often by 9 percent (CI, -2 to 20) to 19 percent (CI, 8-30) in orlistat-treated participants than controls.89,91,96
In 1 trial comparing drug and lifestyle interventions, those treated with metformin lost 2 kg more than those given a placebo but lost less than participants in the lifestyle arm.81 Another trial showed no metformin effect.97 A multidrug trial showed sibutramine-treated people lost significantly more weight (13.4 kg) than those treated with orlistat (8 kg) or metformin (9 kg).98
Maintenance studies showed moderate success. In 1,84 sibutramine, taken 6 months for weight loss and 18 months for weight maintenance, promoted a net 4-kg (CI, 2.4-5.6) loss versus placebo. A corresponding 44 percent (CI, 37-50) of sibutramine versus 16 percent (CI, 6-25) of placebo participants maintained 80 percent of initial weight loss. Likewise, successful dieters treated with orlistat lost more weight and over 1 year were more likely to maintain 75 percent of their initial loss than those treated with placebo (P < 0.05).92 In a third trial, participants treated with 1 or 2 years of orlistat lost "significantly more" weight over 2 years than placebo participants.93 However, during the second year, orlistat was no more effective than placebo, and discontinuing therapy with the drug led to excess weight gain (e.g., mean weight gain during the second year among those who discontinued orlistat was 6.3 kg versus 3.1 kg among those who took placebo throughout).93
Overall, pharmacotherapy with sibutramine and orlistat promoted modest mean weight loss (3-5 kg) beyond that of controls; prolonged drug courses helped sustain this loss up to 2 years. Phentermine and mazindol had similar short-term efficacy but are not approved for long-term use.31 Metformin, diethylpropion, and fluoxetine showed mixed efficacy.
Surgical obesity treatment is limited to patients with BMIs exceeding 40 kg/m2 or patients with BMIs of 35 kg/m2 or more who have associated severe health complications and have not responded to other treatment modalities.99 Bariatric surgery is restrictive or malabsorptive, and current techniques are primarily restrictive. Gastric bypass involves complete gastric partitioning with anastomosis of the proximal gastric segment to a jejunal loop. Adjustable gastric banding involves placing an inflatable band around the stomach that can be adjusted to different diameters.100 Vertical banded gastroplasty entails partial gastric partitioning at the proximal gastric segment with placement of a gastric outlet stoma of fixed diameter.28 Practice patterns appear to be shifting away from this technique. These procedures can be performed open or laparoscopically. Although the duodenal switch procedure—a relatively new malabsorptive technique—is fairly common in practice, we found no RCTs evaluating its effectiveness.
Because of practical and ethical constraints to a true randomized, blinded, placebo-controlled trial of surgery for obesity, high-quality evidence is limited. The 3 prior systematic reviews of obesity therapy primarily examined randomized unblinded trials comparing surgical techniques (e.g., no non-surgical controls).
The NIH reviewed 5 randomized trials, finding 10 to 159 kg of surgical weight loss over 12 to 48 months in patients receiving surgery (Table 1).11 Of 7 U.K. NHS-reviewed trials, 6 showed weight loss with both gastric bypass (mean reduction, 45-65 kg) and gastroplasty (mean reduction, 30-35 kg).29 The CTFPHC analyzed 4 surgical randomized trials and 1 prospective cohort study28 and found a mean weight loss of 17 to 46 kg after 2 to 5 years.
We identified 3 additional randomized trials, all evaluating gastric banding over 1 to 2 years (Table 4).100-102 In addition to lack of non-surgical controls, quality concerns included lack of cointerventions and comorbidity information. None showed significantly different weight loss between arms, but all treatments promoted considerable loss (17 to > 40 kg).
In addition, we identified a large, controlled, cohort study evaluating surgery efficacy: the Swedish Obese Subjects (SOS) study,103,104 a multi-center trial of surgical patients (equally divided among gastric banding, vertical banded gastroplasty, and gastric bypass) and nonrandomized, matched, non-surgical controls.104 At 2 years, weight loss was 28 kg (CI, 26.9-29.1) among surgical patients versus 0.5 kg (CI, -0.2 to 1.2) among controls. Weight reduction after gastric banding, vertical banded gastroplasty, and gastric bypass was 21 percent (standard deviation [SD] 12), 23 percent (SD 10), and 33 percent (SD 10), respectively. After 8 years, a subset analysis showed an average 20-kg (CI, 18.0-22.0) weight loss for 251 surgical patients and a 0.7-kg (CI, -0.8 to 2.2) loss for 232 controls.104 Overall, surgery promoted substantial, prolonged weight loss (10-159 kg over 1-5 years) in patients with extreme obesity.
The NIH systematic review established that counseling-based weight loss (generally 5-10 kg) can improve intermediate health outcomes such as blood pressure, glycemic control, and serum lipids.11 We assessed the effect of pharmacotherapy-associated weight loss on serum lipids and glucose. Since the prior drug review did not cover these outcomes, we abstracted these data from the primary literature it covered, in addition to the more recent articles.
We found mixed evidence for improved glucose tolerance with sibutramine-induced weight loss.32,33,84,86,87,105 Orlistat generally,90,96,106-109 but not always,110 improved glucose parameters. This inconsistency may in part be due to medication alterations accompanying weight loss; in 1 trial, orlistat-treated patients with diabetes were more likely (17 percent vs 8 percent, P < 0.05) to decrease or discontinue diabetes medications than controls,90 and glycosylated hemoglobin was reduced only when adjusted for these alterations.
Seven trials and 1 review linked orlistat with total cholesterol reduction.90,92,106-111 Sibutramine showed less consistent total cholesterol findings: no significant drug versus placebo effect in 6 trials,33,84,86,87,112,113 improvement in 3 others.32,114,115 Orlistat was frequently (but not always)116 associated with reduced low-density lipoprotein (LDL) cholesterol.90,92-94,96,106-108,110,115 Sibutramine had inconsistent LDL effects.32,84-86,90,96,113,114 Neither drug consistently affected high-density lipoprotein cholesterol32,33,90,96,105,113,114,116,117 or triglycerides.33,84-87,90,94,96,105,107,110,112-114
Surgical cohort studies suggest that large amounts of weight loss may lead to dramatic improvements in glucose metabolism,118 lipid profiles,119,120 and blood pressure. Notably, hypertension tended to recur within 3 to 10 years in the SOS group121; although weight regain accompanied this recurrence, all surgical groups had maintained at least a 20-kg average loss.
We found less evidence for effects of weight loss on ultimate (generally symptomatic) health outcomes. Limited observational data suggest intentional weight loss in obese persons (particularly in those with co-morbidity) can reduce mortality.122,123 Two large RCTs show that behaviorally mediated weight loss can prevent diabetes (58-percent reduction, P < 0.05) among those with glucose intolerance.67,81 A smaller (31 percent; CI, 17-43), reduction in diabetes incidence was seen among similar metformin-treated patients.81 Patients treated surgically (non-RCT data) may experience diabetes resolution (e.g., 90-percent followup of 300 surgical patients, initially 50 percent glucose intolerant, initially 50 percent with diabetes, showed 91 percent to have normal fasting glucose and glycosylated hemoglobin).118,120 Likewise, lower diabetes incidence over 2 years (odds ratio 0.10; CI, 0.03-0.28) was seen in the SOS surgical patients versus non-surgical patients.121
Difficulty sustaining weight loss has raised concern that cycles of loss followed by regain potentially carry risk. Observational studies examining weight cycling and mortality show mixed results124-130; conclusions are primarily limited by failure to distinguish between intentional and unintentional weight loss. Some studies examining weight cycling with intentional weight loss have found unfavorable effects on coronary heart disease and its risk factors,131,132 but others have not.133,134 This literature is further limited by joint consideration of participants with diverse baseline age or weight (e.g., not restricted to those with excess weight, some data suggest weight-cycling risk increases inversely with BMI, so is minimized among the obese), and measurement issues (e.g., self-recalled weight, and problems characterizing cycling).135-137 We did not find studies or prior reviews addressing harms of screening or counseling interventions. Some risk is likely present, particularly as obesity stigma is well established.138-140
Sibutramine and orlistat both entail frequent, although typically not serious, adverse effects. Sibutramine's common side effects include insomnia, nausea, hypertension, dry mouth, dizziness, and confusion.31 In the previously reviewed studies, common adverse effects occurred in 10 percent to 30 percent of sibutramine patients versus 8 percent to 19 percent of control patients.31 Among recent RCTs, side effects were common (11-79 percent),86-88 but incidence was similar across treatments. Sibutramine's most worrisome side effects are cardiovascular, including increased blood pressure (mean, 0.0 mm Hg-3.5 mm Hg,31,86-88 or 5 percent84,88) and heart rate (mean, 4-6.8 beats per minute [bpm]).31-33,85,87 In 1 study, elevated diastolic blood pressure (> 5 mm Hg) or pulse (> 10 bpm) occurred in 18 percent more sibutramine-treated participants than controls.33 In people with controlled hypertension, clinically significant blood pressure increases were similar across treatment groups,31 but some individuals experienced marked blood pressure rise.31,86 When reported, dropout due to hypertension was up to 3.9 percent higher among those treated with sibutramine than among those not treated; overall, dropout for adverse events were similar in drug and placebo arms.84,86-88
Adverse events were reported in 7.4 percent to 18 percent more participants receiving orlistat than participants receiving placebo.31,89,91,94 Most symptoms were gastrointestinal, including oily spotting, flatulence, and fecal urgency; these were reported by 22 percent to 95 percent of orlistat users (1-37 percent more often than controls).89-92,96 Other problems have included need for vitamin supplementation and reduced contraceptive pill absorption.31 In recent trials, dropout from side effects was often more common (by 0-12 percent) in orlistat-treated participants.89,90,92,94,96 The metformin RCTs we reviewed did not report dropout due to drug effects; gastrointestinal symptoms were noted to be more common (77.8/100 person years vs 30.7/100 person years) in 1 trial141 and present (in 4 percent) but transient in another. In the latter trial, mean lactic acid values did not rise.97 Prior review of other weight loss medications found no evidence of serious adverse reactions for phentermine. However, case reports suggested potentially serious side effects of pulmonary hypertension with mazindol and diethylpropion therapy and psychosis with mazindol therapy.142
Because of limited surgical RCT data, we evaluated surgical adverse effects in case series reports. Adverse effects were both general (e.g., need for prolonged followup, multivitamin supplementation) and procedure-specific. The gastric banding RCTs did not report mortality; 1 showed lower surgical complications with laparoscopic versus open procedures,100 while the 2 evaluating band placement site present conflicting data regarding relative safety of esophagogastric versus gastric placement (Table 4).101,102 Reported symptoms suggest low rates of dysphagia, hunger, vomiting, and esophagitis.101,102 In the nonrandomized, controlled SOS study, complications were not reported by procedure; post-operative mortality was 0.2 percent and morbidity included bleeding (0.9 percent), wound complications (1.8 percent), abdominal infection (2.1 percent), thromboembolic events (0.8 percent), pulmonary symptoms (6.2 percent), and miscellaneous events (4.8 percent).104
In 38 surgical case series, at least 3 (evaluating vertical banded gastroplasty and gastric bypass) included patients with substantial comorbidities143-145; multiple studies included those with modest health problems. Generally, mortality rates were low. In 12 vertical banded gastroplasty cohorts, the perioperative mortality rate ranged from 0 percent to 1.5 percent (pooled data, 6 deaths in 1,165 patients).143,145-155 Similar rates were seen among gastric bypass patients 0-1.5 percent per series)118,144,149,156-161 and adjustable gastric banding patients (0-1.5 percent).100,102,155,162-176 Morbidity was more common. Vertical banded gastroplasty's main complications were reoperation (20-25 percent over 3-5 years)148,151 and wound infection (8-32 percent of patients).145,148,149 Less frequent events (< 6 percent) included gastric leaks, stomal stenosis, and pouch dilatations. In gastric bypass patients, wound infection was reported in 8 percent to 20 percent.149,159,160 Single studies noted staple failure (15 percent),118 vitamin B12 deficiency (40 percent),118 diarrhea (13 percent),160 and gastrointestinal hemorrhage (3 percent).149 Adjustable gastric banding patients' morbidity was often re-operation (1-20 percent)102,162,165,168-170,175,177,178 band dislocation, leakage, or slippage (0.4-8 percent).100,163-165,167,168,170-172,177,178