Changes in weight and metabolic parameters during treatment with antipsychotics and metformin: do the data inform as to potential guideline development? A systematic review of clinical studies

Abstract

Summary Background: Changes in weight and metabolic parameters have been commonly reported in patients with schizophrenia. Metformin has been evaluated in clinical studies to prevent or reduce weight gain and changes in metabolic parameters in non‐diabetic subjects. We undertook a systematic review of the efficacy and safety of metformin in reducing weight gain and metabolic abnormalities in non‐diabetic subjects with schizophrenia or bipolar disorder taking antipsychotic medication to establish if these data could potentially drive guideline development. Methods: Medical databases were searched using terms including ‘antipsychotic’, ‘atypical antipsychotic agent’, ‘antipsychotic agents’, ‘antipsychotic‐drug’ and ‘metformin’ and ‘weight’. Studies reporting weight and/or metabolic outcomes in non‐diabetic subjects with schizophrenia and bipolar disorder were included regardless of methodological type and subject age. Results: Nine randomised double‐blind studies and two open cohort studies evaluating metformin and changes in weight in trials up to 16 weeks were identified. In all, 495 participants received antipsychotics (mostly olanzapine), and three studies were in subjects aged < 18 years. The adult studies predominantly utilised non‐Caucasian subjects with chronic schizophrenia. Weight and lifestyle intervention programmes were provided to all cohorts in eight studies, which confounded interpretation of the data. In ten studies, the addition of metformin to antipsychotic treatment was associated with either significantly attenuated weight gain or weight loss compared with control groups. Nine studies measured various glucose parameters. In four studies, subjects prescribed metformin had significantly improved glucose parameters relative to controls. The two studies of metformin in patients with first‐episode schizophrenia demonstrated the largest improvement in weight and glucose parameters. Conclusions: Metformin may have some value in reducing or preventing weight gain and changes in metabolic parameters during treatment with antipsychotic medication particularly in first‐episode psychosis; however, it has been predominantly studied short‐term and in non‐Caucasian populations. A number of new trials are due to report data 2009–2013 to aid definitive interpretation of the role of metformin. Further longer‐term studies are warranted before definitive guidelines can be established.

Altered metabolic parameters in association with antipsychotic medication use in diabetes: A population based case-control study

“…Patients prescribed anti-psychotic medication are more likely to develop diabetes (Bushe et al, 2009;Haddad, 2004), but this study aims to determine how their diabetes progresses after diagnosis. Diabetes induced by anti-psychotic medication may have different features to diabetes developing de novo.…”

“…The effect size for medication differences is small. Metformin may limit antipsychotic induced weight gain (Bushe et al, 2009;Ellinger et al, 2010), and Scottish Intercollegiate Guideline Network (SIGN) guidelines recommend consideration of metformin in those experiencing such drug induced weight gain (regardless of diabetes diagnosis) (Scottish Intercollegiate Guidelines Network (SIGN), 2013). These 2013 guidelines may influence future prescribing habits but should not have impacted on this 2010 data extract.…”

Role of metformin in the management of antipsychotic-induced weight gain

“…Findings from these systematic reviews are briefly summarised in Table 2 2,3,[14][15][16]18 and in Table 3. 9,10,17,19,20 Most of the systematic reviews on metformin were based on eight randomised controlled trials (RCTs). Six trials involved adults (see Table 4) [21][22][23][24][25][26] and two trials related to paediatrics (details can be found elsewhere).…”

“…Newall et al (2012) 20 8 If weight gain occurs with secondgeneration antipsychotics, despite lifestyle intervention, metformin should be considered Lee et al (2011) 17 8 Limited evidence of efficacy Ellinger et al (2010) 9 6 Metformin results in greater weight loss than topiramate and may be an option after lifestyle and dietary changes have failed Bushe et al (2009) 19 9 Significant reduction in weight and BMI. Metformin dose 500-3400mg/day Baptista (2008) 10 7 Metformin has a conflicting evidence for prevention, but good evidence for treatment of antipsychoticinduced weight gain RCTs = randomised controlled trials Table 4.…”

Medical Therapy for the Patient With Obesity

“…14 Metformin has been used to reduce weight gain in people treated with antipsychotic drugs. In a systematic review, Bushe et al 35 found that metformin may have some value in reducing or preventing weight gain and change in metabolic parameters during treatment with antipsychotic medications.…”