Multi-Strain Probiotic Reduces Gastrointestinal Side Effects in Women with Elevated HOMA-IR Index Treated with Metformin: A 12-Week Randomised Controlled Trial

Marzena Ratajczak^1,2*Agnieszka Bilska³Katarzyna Musialik⁴Karolina Skonieczna-Żydecka⁵Igor Łoniewski⁶Anna Gogojewicz³Joanna Karolkiewicz³

• ¹Poznan University of Physical Education, Poznan, Poland
• ²Department of Medical Biology, Poznan University of Physical Education, Poznan, Poland
• ³Department of Food and Nutrition, Poznan University of Physical Education, Poznan, Poland
• ⁴Uniwersytet Medyczny im Karola Marcinkowskiego w Poznaniu Katedra i Zaklad Leczenia Otylosci i Zaburzen Metabolicznych oraz Dietetyki Klinicznej, Poznań, Poland
• ⁵Department of Biochemical Research, Pomeranian Medical University, Szczecin, Poland
• ⁶Sanprobi Sp. z o.o. Sp.K., Szczecin, Poland

Background: 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. Methods: 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. Results: 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. Conclusion: 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 coadministration may therefore improve tolerability and adherence to metformin therapy.