Department of Internal Medicine, Diabetology and Nephrology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, Poniatowskiego 15, 40-055 Katowice, Poland.
Department of Biochemical Sciences, Pomeranian Medical University, 71-460 Szczecin, Poland.
Biomed Pharmacother. 2023 Dec;168:115650. doi: 10.1016/j.biopha.2023.115650. Epub 2023 Oct 7.
For decades, metformin has been the drug of first choice in the management of type 2 diabetes. However, approximately 2-13% of patients do not tolerate metformin due to gastrointestinal (GI) side effects. Since metformin influences the gut microbiota, we hypothesized that a multi-strain probiotics supplementation would mitigate the gastrointestinal symptoms associated with metformin usage.
This randomized, double-blind, placebo-controlled, single-center, cross-over trial (ProGasMet study) assessed the efficacy of a multi-strain probiotic in 37 patients with metformin intolerance. Patients were randomly allocated (1:1) to receive probiotic (PRO-PLA) or placebo (PLA-PRO) at baseline and, after 12 weeks (period 1), they crossed-over to the other treatment arm (period 2). The primary outcome was the reduction of GI adverse events of metformin.
37 out of 82 eligible patients were enrolled in the final analysis of whom 35 completed the 32 weeks study period and 2 patients resigned at visit 5. Regardless of the treatment arm allocation, while on probiotic supplementation, there was a significant reduction of incidence (for the probiotic period in PRO-PLA/PLA-PRO: P = 0.017/P = 0.054), quantity and severity of nausea (P = 0.016/P = 0.024), frequency (P = 0.009/P = 0.015) and severity (P = 0.019/P = 0.005) of abdominal bloating/pain as well as significant improvement in self-assessed tolerability of metformin (P < 0.01/P = 0.005). Moreover, there was significant reduction of incidence of diarrhea while on probiotic supplementation in PRO-PLA treatment arm (P = 0.036).
A multi-strain probiotic diminishes the incidence of gastrointestinal adverse effects in patients with type 2 diabetes and metformin intolerance.
几十年来，二甲双胍一直是 2 型糖尿病管理的首选药物。然而，由于胃肠道（GI）副作用，约有 2-13%的患者无法耐受二甲双胍。由于二甲双胍会影响肠道微生物群，我们假设多菌株益生菌补充剂将减轻与使用二甲双胍相关的胃肠道症状。
这项随机、双盲、安慰剂对照、单中心、交叉试验（ProGasMet 研究）评估了多菌株益生菌在 37 名不耐受二甲双胍的患者中的疗效。患者被随机分配（1:1）接受益生菌（PRO-PLA）或安慰剂（PLA-PRO）治疗，并在基线和 12 周后（第 1 期）交叉到另一个治疗组（第 2 期）。主要结局是减少二甲双胍的胃肠道不良事件。
82 名符合条件的患者中有 37 名进入最终分析，其中 35 名完成了 32 周的研究期，2 名患者在第 5 次就诊时退出。无论治疗组分配如何，在接受益生菌补充的同时，恶心的发生率（PRO-PLA/PLA-PRO 的益生菌期：P=0.017/P=0.054）、数量和严重程度、腹胀/腹痛的频率（P=0.009/P=0.015）和严重程度（P=0.019/P=0.005）均显著降低，并且患者对二甲双胍的耐受性自我评估也显著改善（P<0.01/P=0.005）。此外，在 PRO-PLA 治疗组中，益生菌补充时腹泻的发生率也显著降低（P=0.036）。
多菌株益生菌可减少 2 型糖尿病和二甲双胍不耐受患者胃肠道不良反应的发生率。
