Heart and Metabolism

Diets, medications, and surgery

Maria L. Collazo-Clavell
Mayo Clinic, Rochester, Minn, USA
Correspondence: Dr Maria L. Collazo-Clavell, Department of Endocrinology, Metabolism and Nutrition, Mayo Clinic, 200 1st St SW, Rochester, MN 55905, USA.
Tel: +1 507 284 0051, fax: +1 507 284 5745, e-mail: CollazoClavell.Maria@mayo.edu

Abstract

The rising prevalence of obesity, defined as a body mass index >30 kg/m2, has prompted the need for effective interventions. Unfortunately, weight loss programs are associated with high rates of recidivism. This paper reviews the current literature with regard to the use of diets, medications, and surgery in the management of obesity. Clinical application of these interventions is dependent on a good understanding of their efficacy and potential complications.
- Heart Metab. 2002;17:20–25.

Keywords: Obesity, weight loss, bariatric surgery

Introduction
Obesity is defined as a body mass index (BMI) >30 kg/m2 and is becoming more prevalent worldwide. It is associated with multiple medical complications including type 2 diabetes mellitus, hypertension, and dyslipidemia. Modest weight loss (5% to 10%) has been shown to reduce the risks for many associated complications [1]. However, weight loss remains a challenging endeavor. A successful weight loss program encompasses long-term dietary modification with caloric restriction, an increased level of physical activity, and changing behaviors that are counterproductive to weight management. Novel medical therapies and current surgical procedures offer important therapeutic alternatives in the management of obesity.

Diets
A diet prescription remains the cornerstone of weight loss therapy. Two dietary treatments frequently studied are low calorie diets (LCD) and very low calorie diets (VLCD). An LCD is defined as a daily caloric intake ranging from 1000 to 1500 kcal/day. Caloric restriction can be achieved in various ways, commonly by limiting the intake of fat or by decreasing the portion size of various nutrients. Most studies have reported an average weight loss of 8% from initial weight in clinical trials ranging from 3 to 12 months’ duration [1]. A VLCD is a more restrictive regimen (<800 kcal/day) completed under medical supervision. It is associated with a greater initial weight loss (15% to 20%) when compared with LCD. However, VLCD have a higher rate of weight regain and have not been shown to be more effective than LCD after 1 year of therapy [2, 3]. Improved outcomes of VLCD have been reported when combined with behavioral therapy and, most recently, sibutramine [4]. It is unknown if these interventions will improve the clinical utility of VLCD.

Medications
Two medications are currently available for the prolongued management of obesity: sibutramine and orlistat. Pharmacotherapy can be considered in individuals with a BMI >30 kg/m2 or >27 kg/m2 in the presence of medical complications that would benefit from weight loss [1]. Drug selection is guided by potential side effects, contraindications to their use, and their impact on an individual patient. The initiation of medical therapy should not be an isolated intervention. It should be combined with guidance regarding dietary modification, physical activity, and behavioral therapy to help change behaviors counterproductive to weight loss. Regular visits should monitor progress and potential side effects of medication. A multidisciplinary team involving physicians, dietitians, psychologist, and, when deemed necessary, exercise physiologists best accomplishes this.
Sibutramine is a serotonin and adrenaline reuptake inhibitor shown to promote satiety. Dosages of 10 mg and 15 mg daily led to a statistically significant weight loss when compared with placebo after 12 months (Figure 1) [5].

Figure 1. Weight changes observed during a 12-month trial of sibutramine 10 mg (n = 81) or 15 mg (n = 94), and placebo (n = 80) [5].

Sibutramine is also superior to placebo at promoting weight maintenance at doses up to 20 mg/day (Figure 2) [6].

Figure 2. Percentage of patients maintaining a greater than 5% weight loss with sibutramine (n = 350) vs placebo (n = 114) over a 24-month period (*P < 0.001) [6].

Clinical efficacy can be determined early in a therapeutic trial. “Nonresponders” who failed to achieve a 1% weight loss at 4 weeks did not experience additional weight loss despite continued therapy. Common side effects included dryness of the mouth, constipation, and insomnia. A significant rise in blood pressure was observed in some subjects and this should be routinely monitored [5]. Sibutramine should be used with caution with other preparations that influence serotonin metabolism due to the potential risk for “serotonin syndrome,” a condition caused by central and peripheral serotonergic hyperstimulation.
Orlistat is a gastric and pancreatic lipase inhibitor that inhibits the breakdown and absorption of dietary fat [7]. At current recommended doses of 120 mg three times per day it is associated with malabsorption of 30% of ingested fat, which can provide a caloric deficit of about 200 kcal/day. Double-blind placebo-controlled trials have shown orlistat to be superior to placebo at promoting weight loss for up to 1 year (Figure 3).

Figure 3. Mean percentage change in weight with orlistat during an initial 12-month weight loss period followed by a 12-month weight maintenance phase [8]. SB, Single-blind; DB, double-blind.

Orlistat was also statistically superior to placebo in promoting weight maintenance (Figure 4) [8–10].

Figure 4. Percentage of patients losing 5% or greater of their initial body weight during three orlistat trials [8–10].

In a study by Sjöström et al [8], the cohort initially treated with placebo and later randomized to orlistat experienced the best outcome. Their weights continued to decrease to a final weight not statistically different to that of the subjects who remained on orlistat for the full 2-year study. This strongly suggests that this medication is most effective in individuals who have already established lifestyle changes in enhancing continued weight loss.
The most common side effects were gastrointestinal and were influenced by the amount of dietary fat.
Decreased vitamin levels were observed during clinical studies. No vitamin deficiencies were reported and the changes initially observed were corrected with administration of a daily multivitamin.

Surgery
Bariatric surgery has been available for decades, although the procedures performed have varied over the years. Initial aggressive surgeries such as the jejunoileal bypass were associated with significant weight loss, however the metabolic complications limited its continued clinical application [11]. The surgical procedures available today follow two basic principles to promote weight loss: gastric restriction limiting food intake with or without intestinal bypass promoting either a “dumping physiology” or less vigorous malabsorption.
Patient selection is a rigorous process.

Table I. Recommended criteria for patient selection when considering bariatric surgery.

It serves to assure an individual patient fulfills accepted criteria (Table I), provides informed consent regarding risk and benefits of intervention, and hopes to prepare patients, medically and psychologically, to improve long-term outcome and minimize risks. The most common bariatric procedures performed today include the vertical banded gastroplasty (Figure 5), Roux-en-Y gastric bypass (Figure 6), and the biliopancreatic bypass (Figure 7).

Figure 5. Vertical banded gastroplasty.

Figure 6. Roux-en-Y gastric bypass surgery procedure.

Figure 7. Biliopancreatic diversion.

All three procedures lead to significant weight loss, often with improvement of pre-existing metabolic complications (Table II) [12–15]. Gastric restrictive surgeries are associated with less weight loss and higher rates of recidivism, and as a result are less commonly performed [13].
Surgeries leading to nutrient malabsorption lead to greater weight loss but at the risk of nutritional deficiencies. Deficiencies in iron, folate, vitamin B12, and fat-soluble vitamins have been reported after Roux-en-Y gastric bypass and biliopancreatic diversion [12, 15]. Routine vitamin supplementation and careful monitoring for potential deficiencies is recommended. Protein deficiency is a common finding after biliopancreatic diversion. Hypoalbuminemia is reported in 20% of patients 6 months after surgery. Despite dietary counseling to optimize the intake of protein calories, the yearly revision rate because of hypoalbuminemia is 0.1% [12].
Bariatric surgery has a perioperative mortality of less than 1% and the incidence of perioperative complications is <2%. Later complications such as incisional hernias and gallbladder disease range between 10% and 30% [12–16].
These procedures are now offered laparoscopically with decreased perioperative morbidity and decreased length of hospital stay. However, reoperation rates for device-related complications are higher [17].

Table II. Weight loss reported by various bariatric surgical procedures [13–15].

Despite the risks, bariatric surgery is currently the most effective therapy for medically complicated obesity.

Summary
The prevalence of obesity and its associated morbidity has prompted the need for effective weight loss therapy. Sustained lifestyle changes such as dietary modification are imperative for long-term success but have been plagued by high rates of recidivism. To date, the best dietary prescription is one leading to modest caloric restriction since more aggressive VLCD have not been proven to be more efficacious in the long term. Sibutramine and orlistat offer effective therapeutic alternatives to facilitate weight loss when the basic components of a weight loss program are in place. Several bariatric procedures currently performed are effective treatments for the carefully selected patient with medically complicated obesity.

REFERENCES
1. National Institutes of Health. Clinical guidelines on the identification, evaluation, and treatment of overweight and obesity in adults — the evidence report. Obes Res. 1998;6(suppl 2):51S–209S.

2: Int J Obes 1989;13 Suppl 2:39-46

Related Articles,

Treatment of obesity by very low calorie diet, behavior therapy, and their combination: a five-year perspective.

Wadden TA, Sternberg JA, Letizia KA, Stunkard AJ, Foster GD.

University of Pennsylvania School of Medicine Department of Psychiatry, Philadelphia 19104.

Seventy-six obese women with a mean age of 42.1 years and weight of 106.0 kg were randomly assigned to one of three treatments: (a) very low calorie diet alone; (b) behavior therapy alone; or their combination (i.e. combined treatment). Weight losses for the three conditions at the end of treatment were 13.1, 13.0, and 16.8 kg, respectively, with losses for combined treatment significantly greater than those for the two other conditions. Weight losses 1 year after treatment were 4.7, 6.6, and 10.6 kg, respectively. A significantly greater percentage of subjects in the behavior therapy alone (36 percent) and combined treatment conditions (32 percent) maintained their full end-of-treatment weight losses than in the very low calorie diet alone condition (5 percent). Five years after treatment, a majority of subjects in all three conditions had returned to their pretreatment weight, and 55 percent of the total sample had received additional weight reduction therapy. The short and long term effects of treatment are discussed in terms of their implications for practice and research.

Publication Types:

Clinical Trial
Randomized Controlled Trial

PMID: 2613427 [PubMed - indexed for MEDLINE]

3: J Consult Clin Psychol 1994 Feb;62(1):165-71