Combination of Metformin and Lifestyle Intervention for Antipsychotic-Related Weight Gain: A Meta-Analysis of Randomized Controlled Trials

Zheng, Wei; Zhang, Qing E.; Cai, Dong Bin; Yang, Xin; Ungvári, Gábor S.; Ng, Chee H.; Wu, Runliu; Xiang, Yu Tao

doi:10.1055/s-0044-101466

Cited by 25 publications

(25 citation statements)

References 42 publications

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“…Of the six included meta‐analyses of metformin, five reported no difference in rates of adverse reactions, while one reported higher rates of nausea/vomiting (NNH=16, 95% CI: 10 to 50, p=0.01) and diarrhoea (NNH=6, 95% CI: 3 to 25, p=0.01). Although there was no difference in rates of dropouts for orlistat, diarrhoea was the main reason for discontinuation of this drug.…”

Section: Resultsmentioning

confidence: 94%

“…Of 3,709 search engine hits, 27 meta‐analyses were included, representing a total of 128 meta‐analyzed trials and 47,231 study participants.…”

Section: Resultsmentioning

confidence: 99%

“…Meta‐analytic data were available for six different non‐pharmacological interventions: individual lifestyle counseling, group lifestyle counseling, cognitive behavioral therapy, psychoeducation, exercise, and dietary interventions. One meta‐analysis investigated the pooled effect of a combined lifestyle and metformin intervention.…”

Section: Resultsmentioning

confidence: 99%

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The impact of pharmacological and non‐pharmacological interventions to improve physical health outcomes in people with schizophrenia: a meta‐review of meta‐analyses of randomized controlled trials

et al. 2019

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We summarized and compared meta-analyses of pharmacological and non-pharmacological interventions targeting physical health outcomes among people with schizophrenia spectrum disorders. Major databases were searched until June 1, 2018. Of 3,709 search engine hits, 27 metaanalyses were included, representing 128 meta-analyzed trials and 47,231 study participants. While meta-analyses were generally of adequate or high quality, meta-analyzed studies were less so. The most effective weight reduction interventions were individual lifestyle counseling (standardized mean difference, SMD=-0.98) and exercise interventions (SMD=-0.96), followed by psychoeducation (SMD=-0.77), aripiprazole augmentation (SMD=-0.73), topiramate (SMD=-0.72), d-fenfluramine (SMD=-0.54) and metformin . Regarding waist circumference reduction, aripiprazole augmentation (SMD=-1.10) and topiramate (SMD=-0.69) demonstrated the best evidence, followed by dietary interventions . Dietary interventions were the only to significantly improve (diastolic) blood pressure (SMD=-0.39). Switching from olanzapine to quetiapine or aripiprazole (SMD=-0.71) and metformin (SMD=-0.65) demonstrated best efficacy for reducing glucose levels, followed by glucagon-like peptide-1 receptor agonists (SMD=-0.39), dietary interventions (SMD=-0.37) and aripiprazole augmentation (SMD=-0.34), whereas insulin resistance improved the most with metformin (SMD=-0.75) and rosiglitazone . Topiramate had the greatest efficacy for triglycerides (SMD=-0.68) and low-density lipoprotein (LDL)-cholesterol (SMD=-0.80), whereas metformin had the greatest beneficial effects on total cholesterol (SMD=-0.51) and high-density lipoprotein (HDL)-cholesterol (SMD=0.45). Lifestyle interventions yielded small effects for triglycerides, total cholesterol and LDL-cholesterol (SMD=-0.35 to -0.37). Only exercise interventions increased exercise capacity (SMD=1.81). Despite frequent physical comorbidities and premature mortality mainly due to these increased physical health risks, the current evidence for pharmacological and non-pharmacological interventions in people with schizophrenia to prevent and treat these conditions is still limited and more larger trials are urgently needed.People with schizophrenia have substantially poorer physi cal health than the general population 14 , which is often attrib uted to an interaction between social circumstances, lifestyle factors and treatment effects 5 . For instance, behavioral re search has demonstrated that people with schizophrenia are less physically active and exhibit more sedentary behavior than the general population 6 , have a higher quantity but lower qual ity of dietary food intake 7 , and increased adverse health behav iors, such as smoking 8 . Additionally, psychiatric treatment with antipsychotics and other commonly prescribed agents, such as mood stabilizers and antidepressants, further increases the risk of physical health conditions 9,10 . Consequently, people with schizophrenia more frequently have cardiometabolic diseases 1113 , respiratory d...

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Section: Resultsmentioning

confidence: 94%

“…Of 3,709 search engine hits, 27 meta‐analyses were included, representing a total of 128 meta‐analyzed trials and 47,231 study participants.…”

Section: Resultsmentioning

confidence: 99%

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The impact of pharmacological and non‐pharmacological interventions to improve physical health outcomes in people with schizophrenia: a meta‐review of meta‐analyses of randomized controlled trials

et al. 2019

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“…At the time of writing, effects on somatic outcomes were not yet available. (Aldossari, 2018;Zheng et al, 2019), and medication for smoking cessation. It could also be relevant to carefully consider surgical interventions for obesity in selected patients with severe obesity who do not respond to health promotion interventions or pharmacotherapy.…”

Section: Like Our Own Intervention Other Multi-component Health Behamentioning

confidence: 99%

Outcome of a psychosocial health promotion intervention aimed at improving physical health and reducing alcohol use in patients with schizophrenia and psychotic disorders (MINT)

Westman

Eberhard

Gaughran

et al. 2019

Schizophrenia Research

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Background: Life expectancy is reduced by 19 years in men and 17 in women with psychosis in Sweden, largely due to cardiovascular disease.Aim: Assess whether a psychosocial health promotion intervention improves cardiometabolic risk factors, quality of life, and severity of illness in patients with psychotic disorders more than treatment as usual.Methods: A pragmatic intervention trial testing a manual-based multi-component health promotion intervention targeting patients with psychosis. The Swedish intervention was adapted from IMPaCT therapy, a health-promotion program based on motivational interviewing and cognitive behavioral therapy, designed to be incorporated into routine care.The intervention group consisted of 119 patients and a control group of 570 patients from specialized psychosis departments. Outcome variables were assessed 6 months before intervention during the run-in period, again at the start of intervention, and 12 months after the intervention began. The control group received treatment as usual.Results: The intervention had no significant effect on any of the outcome variables. However, BMI, waist circumference, systolic BP, heart rate, HbA1c, general health, and Clinical Global Impressions Scale score improved significantly during the run-in period before the start of the active intervention (observer effect). The multi-component design meant that treatment effects could only be calculated for the intervention as a whole.Conclusion: The results of the intervention are similar to those of the U.K. IMPaCT study, in which the modular health-promotion intervention had little effect on cardiovascular risk indicators. However, in the current study, the run-in period had a positive effect on cardiometabolic risk factors.

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“…Dyslipidemia, such as increased level of total cholesterol, triglyceride, LDL-C and decreased level of high density lipoprotein cholesterol (HDL-C), could occur in around two-thirds of patients with schizophrenia 10 . Lifestyle and dietary interventions has been found to be safe and effective in treating dyslipidemia 11,12 . Several metaanalyses have found that topiramate 12 , metformin 13 , and rosuvastatin 14 were also effective and safe in improving dyslipidemia induced by antipsychotics in schizophrenia.…”

Section: Introductionmentioning

confidence: 99%

Adjunctive metformin for antipsychotic-induced dyslipidemia: a meta-analysis of randomized, double-blind, placebo-controlled trials

et al. 2020

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Antipsychotic-induced dyslipidemia could increase the risk of cardiovascular diseases. This is a meta-analysis of randomized double-blind placebo-controlled trials to examine the efficacy and safety of adjunctive metformin for dyslipidemia induced by antipsychotics in schizophrenia. The standardized mean differences (SMDs) and risk ratios (RRs) with their 95% confidence intervals (CIs) were calculated using the random-effects model with the RevMan 5.3 version software. The primary outcome was the change of serum lipid level. Twelve studies with 1215 schizophrenia patients (592 in metformin group and 623 in placebo group) were included and analyzed. Adjunctive metformin was significantly superior to placebo with regards to low density lipoprotein cholesterol (LDL-C) [SMD: −0.37 (95%CI:−0.69, −0.05), P = 0.02; I 2 = 78%], total cholesterol [SMD: −0.47 (95%CI:−0.66, −0.29), P < 0.00001; I 2 = 49%], triglyceride [SMD: −0.33 (95%CI:−0.45, −0.20), P < 0.00001; I 2 = 0%], and high density lipoprotein cholesterol [SMD: 0.29 (95% CI:0.02, 0.57), P = 0.03; I 2 = 69%]. The superiority of metformin in improving LDL-C level disappeared in a sensitivity analysis and 80% (8/10) of subgroup analyses. Metformin was significantly superior to placebo with regards to decrease in body weight, body mass index, glycated hemoglobin A1c, fasting insulin, and homeostasis model assessment-insulin resistance (P = 0.002-0.01), but not regarding changes in waist circumference, waist-to-hip rate, leptin, fasting glucose, and blood pressure (P = 0.07-0.33). The rates of discontinuation due to any reason [RR: 0.97 (95%CI: 0.66, 1.43), P = 0.89; I 2 = 0%] was similar between the two groups. Adjunctive metformin could be useful to improve total cholesterol and triglyceride levels, but it was not effective in improving LDL-C level in schizophrenia.

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Combination of Metformin and Lifestyle Intervention for Antipsychotic-Related Weight Gain: A Meta-Analysis of Randomized Controlled Trials

Abstract: Combining metformin and lifestyle intervention shows significant effect in reducing AP-related weight gain. Higher quality and larger RCTs are needed to confirm these findings.Review registration: CRD42017059198.

Cited by 25 publications

References 42 publications

The impact of pharmacological and non‐pharmacological interventions to improve physical health outcomes in people with schizophrenia: a meta‐review of meta‐analyses of randomized controlled trials

The impact of pharmacological and non‐pharmacological interventions to improve physical health outcomes in people with schizophrenia: a meta‐review of meta‐analyses of randomized controlled trials

Outcome of a psychosocial health promotion intervention aimed at improving physical health and reducing alcohol use in patients with schizophrenia and psychotic disorders (MINT)

Adjunctive metformin for antipsychotic-induced dyslipidemia: a meta-analysis of randomized, double-blind, placebo-controlled trials

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