Metformin treatment of antipsychotic-induced dyslipidemia: an analysis of two randomized, placebo-controlled trials

Abstract

Dyslipidemia is one of the most common adverse effects in schizophrenia patients treated with antipsychotics. However, there are no established effective treatments. In this study, data were pooled from two randomized, placebo-controlled trials, which were originally designed to examine the efficacy of metformin in treating antipsychotic-induced weight gain and other metabolic abnormalities. In total, 201 schizophrenia patients with dyslipidemia after being treated with an antipsychotic were assigned to take 1000 mg day -1 metformin (n = 103) or placebo (n = 98) for 24 weeks, with evaluation at baseline, week 12 and week 24. The primary outcome was the low-density lipoprotein cholesterol (LDL-C) levels. After metformin treatment, the mean difference in the LDL-C value between metformin treatment and placebo was from 0.16 mmol l -1 at baseline to -0.86 mmol l -1 at the end of week 24, decreased by 1.02 mmol l -1 (P o0.0001); and 25.3% of patients in the metformin group had LDL-C ≥ 3.37 mmol l -1, which is significantly o64.8% in the placebo group (P o 0.001) at week 24. Compared with the placebo, metformin treatment also have a significant effect on reducing weight, body mass index, insulin, insulin resistance index, total cholesterol and triglyceride, and increasing high-density lipoprotein cholesterol. The treatment effects on weight and insulin resistance appeared at week 12 and further improved at week 24, but the effects on improving dyslipidemia only significantly occurred at the end of week 24. We found that metformin treatment was effective in improving antipsychotic-induced dyslipidemia and insulin resistance, and the effects improving antipsychotic-induced insulin resistance appeared earlier than the reducing dyslipidemia.

The Effect of Metformin on Antipsychotic-induced Weight Gain in Patients with Schizophrenia or Schizoaffective Disorder: A Systematic Review and Meta-analysis of Randomized Placebo-Controlled Trials

“…Flow of the study selection process for a systematic review and meta-analysis 항정신병약물에 의한 체중증가에 미치는 메트포르민의 영향 / 207 37) 대해 비뚤림 위험을 평가하였다. '무작위 배정 순서 생성' 항 목에서 4개 연구가 24,26,30,37) '불확실'로, 그 외 연구들은 '낮음' 으로 평가되었다. '배정순서 은폐'의 경우도 4개 연구가 24,26,29,30) '불확실'로, 그 외 연구들은 '낮음'으로 평가되었다.…”

“…3). [23][24][25][26][27][28][29][30][31][32][33][34][35][36][37] 또한, 연구 시작 점에 과체중이었던 연구대상자만을 분석했을 때에도 placebo 군에 비해 metformin 군에서 유사한 정도의 체질량지수 감소 가 관찰되었다(WMD: -0.91; 95% CI: -1.11, -0.71; p<0.00001; I 2 : 28%). 24,25,28,[31][32][33][34][35][36] 더하여, 소아를 대상으로 한 연구를 24,26) 배제한 후 연구시작점에서의 체질량지수에 무관하게 성인환 자만으로 분석했을 때, 체중의 경우 소아를 포함했을 때와 거의 차이가 없었다(체중, WMD: -2.17; 95% CI: -2.72, -1.63; p<0.00001; I 2 : 29%; 체질량지수, WMD: -0.89; 95% CI: -1.06, -0.71; p<0.00001; I 2 : 42%) ( Supplementary Fig.…”

“…8). 한편, metformin의 용 량에 따른 효과를 분석하였을 때, 1일 복용량이 850~2,250 mg (고용량)이었던 연구에 [23][24][25][26]28,[30][31][32][33][35][36][37] 비해 500 mg 혹은 750 mg (저용량)이었던 연구에서 27,29,35) 체중 감소가 더 컸으며(저 용량, WMD: -3.29; 95% CI: -4.44, -2.14; p<0.00001; I 2 : 34%; 고용량, WMD: -1.82; 95% CI: -2.37, -1.27; p<0.00001; I 2 : 4%), 마찬가지로 고용량을 사용한 연구에 [23][24][25][26]28,[30][31][32][33][34][35][36][37] 비해 저용량을 사용한 연구에서 27,29,34,35) 체질량지수의 감소도 더 컸다(저용량, WMD: -1.52; 95% CI: -1.87, -1.18; p<0.00001; I 2 : 0%; 고용량, WMD: -0.68; 95% CI: -0.88, -0.47; p<0.00001; I 2 : 0%) (Supplementary S4, S5). 3.6 mg/dL의 감소를 가져왔으며 고밀도지단백 콜레스테롤 (HDL-C)은 0.2% 증가시켰다고 발표했다.…”

Adjunctive Reboxetine for Schizophrenia: Meta-analysis of Randomized Double-blind, Placebo-controlled Trials

“…In the past two decades, weight gain induced by APs has attracted increased attention [11][12][13][14][15][16]. Weight gain is associated with poor treatment adherence and quality of life, higher rate of medical comorbidity particularly cardiovascular diseases, diabetes mellitus, and osteoarthritis and mortality [12,13,[17][18][19][20][21].…”

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.…”