# Multi-strain probiotic reduces gastrointestinal side effects in women with elevated HOMA-IR index treated with metformin: a 12-week randomised controlled trial

## TL;DR

A 12-week study found that a multi-strain probiotic reduced gastrointestinal side effects in women taking metformin for elevated HOMA-IR, without affecting metabolic outcomes.

## Contribution

This is the first trial to show that a multi-strain probiotic can reduce metformin-induced GI side effects in non-diabetic women with elevated HOMA-IR.

## Key findings

- The probiotic group reported fewer GI symptoms like abnormal stool consistency and frequency compared to placebo.
- No significant differences in metabolic markers were observed between the probiotic and placebo groups.
- Both groups improved fasting glucose, HOMA-IR, RBP4, and cholesterol over time, indicating metformin's efficacy.

## Abstract

Metformin is widely used as a first-line therapy for type 2 diabetes and increasingly prescribed off-label in women with elevated HOMA-IR indices, including those at risk of metabolic disorders. However, its clinical use is often limited by gastrointestinal (GI) adverse effects. The present study examined whether a multi-strain probiotic could enhance the metabolic effects of metformin and reduce GI side effects in women with newly identified elevated HOMA-IR.

In this 12-week randomised, placebo-controlled, double-blind trial, 30 women aged 25–45 years with elevated HOMA-IR (≥2.5) and no diagnosis of diabetes were enrolled. All participants were prescribed metformin 1000 mg/day. They were randomised 1:1 to receive either a multi-strain probiotic (2 × 109 CFU/day) or placebo. Outcomes included metabolic markers (glucose, insulin, HOMA-IR, RBP4, lipid profile, body composition) and self-reported GI symptoms.

After 12 weeks, the probiotic group reported significantly fewer GI symptoms compared with placebo, including lower frequency of abnormal stool consistency during abdominal pain (26% vs. 52%, p < 0.05), abnormal stool frequency (18% vs. 51%, p < 0.05), and hard or lumpy stools (Bristol types 1–2; 14% vs. 26%, p < 0.05). No significant between-group differences were observed for metabolic or anthropometric parameters. Both groups showed significant improvements over time in fasting glucose (time effect p < 0.05), HOMA-IR (p < 0.05), RBP4 (p < 0.05), and total cholesterol (p < 0.01), with no significant group × time interactions, indicating effects attributable to metformin rather than probiotic supplementation.

Multi-strain probiotic supplementation did not enhance the metabolic efficacy of metformin in women with elevated HOMA-IR but significantly alleviated GI side effects. Probiotic co-administration may therefore improve tolerability and adherence to metformin therapy.