Meta-analysis of randomized controlled trials of the effects of probiotics on type 2 diabetes in adults

Abstract

Despite advancements in preventive medicine and pharmacotherapy, diabetes remains an overwhelming health problem. Evidence from randomized controlled trials (RCTs) suggests that probiotics may offer beneficial effects on glycemic control. Our objective was to perform a systematic review and meta-analysis of RCTs to quantify the effect of probiotic administration on glycemic homeostasis in type 2 diabetes. Medline, Web of Science, Google Scholar, and Cochrane Central Register of Controlled Trials were searched for relevant trials published until October 12, 2021. RCTs that lasted ≥3 weeks and assessed the effects of probiotics on the markers of glycemic homeostasis in type 2 diabetes were included. Data were pooled using the generic inverse variance method and expressed as mean differences (MDs) with 95% confidence intervals (CIs). Heterogeneity was assessed using Cochran's Q statistic and quantified using the I2 statistic. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to evaluate the certainty of evidence. A total of 33 eligible trial comparisons (n=1927) were included in this meta-analysis. Our results revealed that compared with placebo, a median probiotic dose of ∼109cfu/day significantly reduced the glycated hemoglobin (HbA1c) levels (MD:-0.19% [95% CI:-0.32,-0.07]; P=0.003), fasting blood glucose levels (MD:-1.00mmol/L [95% CI:-1.45,-0.56]; P<0.0001), fasting insulin levels (MD:-5.73pmol/L [95% CI:-12.17, 0.72]; P=0.08), and HOMA-insulin resistance (IR) (MD:-1.00 [95% CI:-1.32,-0.68]; P<0.00001). The certainty of evidence was graded low for HbA1c and fasting glucose, moderate for fasting insulin, and high for HOMA-IR. Probiotic supplements do not induce clinically significant reductions in HbA1c levels, but lead to marginally clinically significant reductions in fasting glucose and fasting insulin levels in patients with type 2 diabetes. Compared with single-strain and low-dose probiotics, multi-strain and high-dose probiotics have a greater beneficial effect on glycemic homeostasis. In addition, probiotic treatment may be more effective in patients with a high baseline body mass index and age.