Department of Internal Medicine, Division of Endocrinology, American University of Beirut Medical Center, Beirut, Lebanon.
Faculty of Medicine, American University of Beirut Medical Center, Beirut, Lebanon.
Diabetes Obes Metab. 2024 May;26(5):1850-1867. doi: 10.1111/dom.15501. Epub 2024 Mar 11.
There are conflicting data on the weight-reducing potential of metformin (MTF) in nondiabetic patients with obesity. The purpose of this systematic review and meta-analysis was to evaluate the effect of MTF on weight and cardiometabolic parameters in adults with overweight/obesity with or without nonalcoholic fatty liver disease (NAFLD) (CRD42018085512). We included randomized controlled trials (RCTs) in adults without diabetes mellitus, with mean body mass index (BMI) ≥ 25 kg/m, with or without NAFLD, comparing MTF to placebo/control, lifestyle modification (LSM) or a US Food and Drug Administration-approved anti-obesity drug, reporting on weight or metabolic parameters, and extending over at least 3 months. We conducted a systematic search in MEDLINE, EMBASE, PubMed and the Cochrane Library without time limitation (until March 2022). We screened and selected eligible articles, abstracted relevant data, and assessed the risk of bias. All steps were in duplicate and independently. We conducted a random-effects model meta-analysis using Review Manager version 5.3, with prespecified subgroup analyses in case of heterogeneity. We identified 2650 citations and included 49 trials (55 publications). Compared to placebo, MTF was associated with a significant reduction in BMI (mean difference [MD] -0.56 [-0.74, -0.37] kg/m; p < 0.0001), at doses ranging from 500 to 2550 mg/day, and with a significant percentage change in BMI of -2.53% (-2.90, -2.17) at the dose 1700 mg/day. There was no interaction by baseline BMI, MTF dose or duration, nor presence or absence of NAFLD. There was no significant difference between MTF and LSM. Orlistat was more effective than MTF (at doses of 1000-1700 mg/day) in terms of weight loss, with an MD in BMI of -3.17 (-5.88; -0.47) kg/m, favouring the former. Compared to placebo/control, MTF improved insulin parameters, while no effect was detected when compared to LSM. A few small trials showed heterogenous effects on liver parameters in patients with NAFLD treated with MTF compared to placebo/control. There was a large variability in the expression of outcome measures and RCTs were of low quality. In conclusion, MTF was associated with a modest weight reduction in obese nondiabetic patients. Further high-quality and better powered studies are needed to examine the impact of MTF in patients with insulin resistance and NAFLD.
在非糖尿病肥胖患者中，二甲双胍（MTF）的减重潜力存在相互矛盾的数据。本系统评价和荟萃分析的目的是评估 MTF 对超重/肥胖伴或不伴非酒精性脂肪性肝病（NAFLD）（CRD42018085512）成年人的体重和心脏代谢参数的影响。我们纳入了没有糖尿病的成年人的随机对照试验（RCT），平均体重指数（BMI）≥25kg/m，伴或不伴 NAFLD，将 MTF 与安慰剂/对照、生活方式改变（LSM）或美国食品和药物管理局批准的减肥药进行比较，报告体重或代谢参数，并至少持续 3 个月。我们在没有时间限制的情况下（截至 2022 年 3 月）在 MEDLINE、EMBASE、PubMed 和 Cochrane 图书馆中进行了系统搜索。我们筛选并选择了合格的文章，提取了相关数据，并评估了偏倚风险。所有步骤均为双盲且独立进行。我们使用 Review Manager 版本 5.3 进行了随机效应模型荟萃分析，并在存在异质性的情况下进行了预设的亚组分析。我们确定了 2650 条引文，并纳入了 49 项试验（55 篇文献）。与安慰剂相比，MTF 与 BMI 的显著降低相关（平均差异 [MD]-0.56[-0.74，-0.37]kg/m；p<0.0001），剂量范围为 500 至 2550mg/天，并且在 1700mg/天的剂量下，BMI 的百分比变化有显著差异，为-2.53%（-2.90，-2.17）。基线 BMI、MTF 剂量或持续时间、是否存在或不存在 NAFLD 之间没有交互作用。MTF 与 LSM 之间没有显著差异。奥利司他（orlistat）在减重方面比 MTF（剂量为 1000-1700mg/天）更有效，BMI 的 MD 为-3.17（-5.88；-0.47）kg/m，前者更有效。与安慰剂/对照相比，MTF 改善了胰岛素参数，而与 LSM 相比，未检测到效果。少数小型试验显示，与安慰剂/对照相比，MTF 治疗 NAFLD 患者的肝脏参数存在异质性影响。结局指标的表达存在很大的变异性，RCT 质量较低。总之，MTF 与肥胖非糖尿病患者的体重适度减轻有关。需要进一步进行高质量和更好的大型研究，以检验 MTF 在胰岛素抵抗和 NAFLD 患者中的影响。
