Lack of evidence for weight loss drugs
The most recent guideline on this topic does not recommend any medication, citing a lack of evidence. In its 2003 consensus statement, a panel representing the American Diabetes Association, American Psychiatric Association, American Association of Clinical Endocrinologists, and the North American Association for the Study of Obesity3 recommends:
- That patients taking second-generation antipsychotics have the following assessments at baseline and regular intervals: weight, height, waist circumference, blood pressure, fasting plasma glucose, and fasting lipids.
- Providing nutrition and exercise counseling to all patients who are over-weight or obese at baseline.
- Initiating treatment with one of the second-generation antipsychotics with a lower risk of weight gain for patients at high risk of diabetes (ie, family history) and for patients who gain 5% or more of their initial weight or develop worsening hyperglycemia or dyslipidemia during treatment.
This guideline does not recommend metformin to reduce weight gain.
A 2007 Cochrane review of interventions to reduce weight gain in patients with schizophrenia included 23 randomized controlled trials of a variety of weight loss interventions, including cognitive/behavioral interventions and a variety of medications, including sibutramine, orlistat, fluoxetine, topiramate, and metformin. The authors highlighted the limited number of studies of short duration and with small sample sizes and concluded that the evidence was insufficient for the use of pharmacologic interventions to prevent or treat weight gain.5
STUDY SUMMARY: Lifestyle changes and metformin compared
This randomized controlled trial was conducted in China and included 128 adults aged 18 to 45 with a first psychotic episode of schizophrenia. All patients had to have gained more than 10% of their pretreatment body weight during the first year of treatment with an antipsychotic medication (clozapine, olanzapine, risperidone, or sulpiride [not approved for use in the United States]). All study participants had to be under the care of an adult caregiver who monitored and recorded food intake, exercise, and medication intake. Patients with diabetes, cardiovascular disease, liver or renal dysfunction, substance abuse, or psychiatric diagnoses other than schizophrenia were excluded.
Patients were randomized to 1 of 4 groups for the 12 weeks of the study:
- Metformin alone, 250 mg 3 times daily
- Placebo alone
- Lifestyle intervention plus metformin
- Lifestyle intervention plus placebo
The lifestyle intervention included 3 components: (1) education: monthly programs on nutrition and physical activity; (2) diet: the American Heart Association step 2 diet (<30% calories from fat, 55% carbohydrates, >15% protein, with at least 15 g fiber per 1000 kcal); and (3) exercise: 1 week of sessions with an exercise physiologist followed by an individualized home-based exercise program.
Primary outcomes included changes in weight, body mass index (BMI), waist circumference, and fasting glucose ( TABLE 2 ). Ten of the 128 randomized patients either discontinued the study or were lost to follow up, but all 128 patients were included in the analysis.
TABLE 2
Mean difference between baseline and endpoint (week 12) of treatment outcomes (95% confidence intervals)1
| LIFESTYLE + METFORMIN | METFORMIN | LIFESTYLE | PLACEBO | |
|---|---|---|---|---|
| Weight, kg | -4.7 (-5.7 to -3.4) | -3.2 (-3.9 to -2.5) | -1.4 (-2.0 to -0.7) | 3.1 (2.4 to 3.8) |
| BMI, kg/m2 | -1.8 (-2.3 to -1.3) | -1.2 (-1.5 to -0.9) | -0.5 (-0.8 to -0.3) | 1.2 (0.9 to 1.5) |
| Waist circumference, cm | -2.0 (-2.4 to -1.5) | -1.3 (-1.5 to -1.1) | 0.1 (-0.5 to 0.7) | 2.2 (1.7 to 2.8) |
| Fasting glucose, mg/dL | -7.2 (-10.8 to -5.4) | -10.8 (-16.2 to -7.2) | -7.2 (-9.0 to -3.6) | 1.8 (-1.8 to 3.6) |
Best result: Lifestyle changes plus metformin
Compared with baseline, weight decreased by 7.3% in the lifestyle plus metformin group, by 4.9% in the metformin-only group, and by 2.2% in the lifestyle-only group; in the placebo group, weight increased by 4.8%.
Participants in all 3 intervention groups also showed significant decreases in the mean fasting glucose, insulin levels, and insulin resistance index (IRI). The insulin levels and the IRI increased in the placebo group.
No significant differences in adverse effects were noted among the 4 treatment groups.1
