Metformin in prevention and treatment of antipsychotic induced weight gain: a systematic review and meta-analysis

Abstract

BackgroundMost antipsychotics are associated with weight gain and other metabolic complications. Several randomized trials have shown metformin to be effective, but this still hasn’t been included in clinical guidelines on managing antipsychotic induced weight gain.MethodsAll double blind placebo controlled trials assessing the efficacy of metformin in the treatment of antipsychotic induced weight gain were included. Cochrane Central Register of Controlled Trials (CENTRAL) and MEDLINE were searched for the period January 2000-December 2015. Meta-analysis was carried out using the random effects model.ResultsMeta analysis of 12 published studies with a total of 743 patients found that in patients treated with antipsychotics, metformin treatment resulted in significantly better anthropometric and metabolic parameters than placebo. The mean change in weight was −3.27 kg (95 % CI −4.66 to −1.89) (Z = 4.64, p < 0.001). Metformin compared to placebo resulted in significant reduction in BMI [−1.13 kg/m2 (95 % CI −1.61 to −0.66)] and insulin resistance index [−1.49 (95 % CI −2.40 to −0.59)] but not fasting blood sugar [−2.48 mg/dl (95 % CI −5.54 to 0.57].ConclusionThis meta-analysis confirms that metformin is effective in treating antipsychotic induced weight gain in patients with schizophrenia or schizoaffective disorder.Electronic supplementary materialThe online version of this article (doi:10.1186/s12888-016-1049-5) contains supplementary material, which is available to authorized users.

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

“…Thus, blood lactate concentration, serum B 12 levels and folate levels should be regularly screened for patients with schizophrenia when they received metformin treatment 2 . Several meta-analyses 11,13,[29][30][31][32][33][34][35][36][37] had examined antipsychotic-induced body weight and metabolic abnormalities in schizophrenia, however, only a small number of them with comparatively smaller sample size meta-analyzed dyslipidemia as a secondary outcome 33,35,37 . This meta-analysis only included double-blind RCTs examining adjunctive metformin for dyslipidemia in schizophrenia, together with a large sample size increase the robustness and reliability of meta-analytic findings.…”

“…Both international (PubMed, Cochrane Library, Psy-cINFO, and EMBASE) and Chinese (Chinese Journal Net, and WanFang) databases were independently searched to obtain relevant published RCTs by three investigators (WLJ, DBC, and FY) from their commencement dates to October 22, 2018, using the search terms as follows: ("metformin"[MeSH] OR metformin OR Dimethylbiguanidine OR Dimethylguanylguanidine OR Glucophage) AND ("dyslipidemias"[MeSH] OR Dyslipidemias OR Dyslipidemia OR Dyslipoproteinemias OR Dyslipoproteinemia OR metabolic OR lipid OR fats OR Hypolipidemic Agents OR cholesterol OR HDL OR LDL OR lipoprotein OR triglyceride OR adiponectin OR ghrelin OR leptin OR resistin OR chemerin OR omentin OR apelin or adipocytokine OR adipokine) AND ("schizophrenia"[Mesh] OR schizophrenic disorder OR disorder, schizophrenic OR schizophrenic disorders OR schizophrenia OR dementia praecox). The references of relevant reviews 11,13,[29][30][31][32][33][34][35][36][37] were also searched manually to avoid missing publications.…”

“…Some reviews and meta-analyses 11,13,[29][30][31][32][33][34][35][36][37] have examined the efficacy and safety of adjunctive metformin for antipsychotics-related weight gain and metabolic abnormalities in schizophrenia. However, the primary outcome in most meta-analyses was weight gain, rather than dyslipidemia, and some meta-analyses included open-label studies, which deviate from the standardized recommendations 38 .…”

Genetic association between antipsychotic induced weight gain and FTO gene in a Sri Lankan population

“…This aspect has not been investigated in detail. Mechanisms of weight gain in first episode patients and those on long term treatment may also differ [24]. Although there are some studies of first episode patients most genetic association studies have used mixed populations.…”

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

“…A meta-analysis found that nutritional counselling (n = 95) was significantly superior to treatment as usual (n = 75) in attenuating AP-related weight gain [16]. In addition, several RCTs [3,[17][18][19] and meta-analyses [2,[20][21][22] have found that metformin is effective, safe, and well tolerated in reducing AP-related weight gain in schizophrenia patients.…”