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Review: several pharmacological therapies promote modest weight loss
  1. Kurt A Kennel, MD
  1. Mayo Clinic, Rochester, Minnesota, USA.

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 Q How effective and safe are pharmacological therapies in the treatment of obesity?

    Clinical impact ratings GP/FP/Primary care ★★★★★☆☆ IM/Ambulatory care ★★★★★☆☆ Endocrine ★★★★★☆☆


    Embedded ImageData sources:

    Medline (to July 2003), the Cochrane Central Register of Controlled Trials, and existing systematic reviews.

    Embedded ImageStudy selection and assessment:

    randomised controlled trials that evaluated pharmaceutical agents for weight loss in patients with body mass index ⩾27 kg/m2 and reported ⩾6 month weight outcomes. Study quality was assessed using the 5 point Jadad scale (5 = highest quality) and considered study design, method of random assignment, blinding, and withdrawal.

    Embedded ImageOutcomes:

    weight loss and side effects.


    The studies meeting inclusion criteria were 3 existing meta-analyses (39 RCTs) evaluating sibutramine, phentermine, and diethylpropion, and 47 RCTs that evaluated orlistat, bupropion, topiramate, and fluoxetine. All comparisons were with placebo, and most trials had a hypocaloric diet cointervention. Meta-analyses were done using random effects. Most medications led to modest weight loss compared with placebo; side effects varied by drug (table).

    Medical therapies v placebo for obesity*


    On average, sibutramine, phentermine, orlistat, diethylpropion, bupropion, topiramate, and fluoxetine led to 1–7 kg of weight loss by 6 months in obese adults with body mass index ⩾27 kg/m2.


    Obesity is a chronic condition resulting from a myriad of factors causing an imbalance of energy intake and expenditure. Although lifestyle changes can result in weight loss for some, many obese patients need more efficacious interventions for weight reduction. The use of pharmacological and surgical treatments has increased in response to the increasing prevalence of obesity.

    Li et al and a Cochrane review on this topic1 agree that several available medications combined with dietary intervention result in average weight loss of about 3–5 kg in excess of placebo with relatively mild short term side effects.

    Although a 5–10% weight loss can result in reduced risk of chronic disease,2 Foster et al showed that most patients achieving the degree of weight loss reported with pharmacotherapy by Li et al would be “very disappointed.”3 A group under-represented in pharmacological trials, severely obese patients (BMI >40 kg/m2) may perceive less palliation from a “modest” weight loss. Large loss to follow up in trials and in clinical practice may, in part, reflect limitations of medical therapy and complicate the interpretation of trials.

    With this in mind, clinicians should appreciate why some patients are enamoured with surgical treatments for obesity. Maggard et al noted that although current, high quality data are lacking, a large observational study from Sweden supports the efficacy and probable superiority of surgical treatments for severely obese patients. When considering the large, consistent differences in weight, major comorbid outcomes observed, and low risk of major complications in a large number of patients, they suggest it is more likely that the differences are attributable to surgical treatment and not due to unmeasured variables. Consistent findings from other investigators have been published.4 Still, RCTs are needed to establish causality and to detect small differences (particularly between surgical procedures) in outcomes important to patients, including quality of life and cost effectiveness.

    Clinicians should consider many variables before generalising these data to patient care as they may not reflect such variables as advancements in surgical techniques, differences in technical skill, refined systems of care (eg, multidisciplinary bariatric surgery teams), patient age, and the addition of cointerventions (eg, behaviour therapy and support groups). Further research needs to explore the largely unexplained differences in results among many of the weight loss therapy trials. These differences suggest that patient populations with specific barriers to effective weight loss or specific comorbid conditions may respond better to different types of weight loss drugs, combinations of drugs, and cointerventions.

    Clinicians should work with patients to define important outcomes, including the magnitude of weight loss, effect on relevant obesity related cormorbid conditions, and cost to identify patients’ tolerance of risk for adverse events and to convey the uncertainty about the available evidence.


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    • For correspondence: Dr Z Li, West LA Veterans Affairs Medical Center, Los Angeles, CA, USA.

    • Source of funding: Agency for Healthcare Quality and Research.

    • Abstract and commentary also appear in ACP Journal Club.