Gastrointestinal adverse events of metformin treatment in patients with type 2 diabetes mellitus: A systematic review, meta-analysis and meta-regression of randomized controlled trials

Abstract

IntroductionMetformin is the first choice drug in the treatment of type 2 diabetes mellitus but its administration may be linked to gastrointestinal adverse events limiting its use.ObjectivesThe objective of this systematic review and meta-analysis was to assess the risk of gastrointestinal adverse events related to metformin use in patients with type 2 diabetes treated with metformin.MethodsPUB MED/CINAHL/Web of Science/Scopus were searched from database inception until 08.11.2020 for articles in English and randomized controlled trials related to patients with type 2 diabetes treated with metformin were included.ResultsFrom 5315 publications, we identified 199 potentially eligible full-text articles. Finally, 71 randomized controlled trials were included in the meta-analysis. In these studies, metformin use was associated with higher risk of abdominal pain, diarrhea and nausea comparing to control. The risks of abdominal pain and nausea were highest comparing to placebo. Bloating risk was only elevated when metformin treatment was compared to DPP4i.ConclusionsThe risk of gastrointestinal adverse events such as abdominal pain, nausea and diarrhea is higher in type 2 diabetes patients treated with metformin compared to other antidiabetic drugs. There is a higher risk of bloating and diarrhea with metformin immediate-release than with metformin extended release formulation.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021289975, identifier CRD42021289975.

Clinical significance of microbiota changes under the influence of psychotropic drugs. An updated narrative review

“…Additionally, A. muciniphila acts in CNS (Cheng et al, 2021;Higarza et al, 2021;Sun et al, 2022). It is therefore postulated that the reconstruction of the microbiota altered by a metabolic disease under the influence of metformin may be functionally beneficial, but in some patients -especially during the period of increasing the dosage -it may cause gastrointestinal disorders (Nabrdalik et al, 2022). The observed side effects may be related to the effect of the drug on the microbiota (MetaHIT consortium et al, 2015;Elbere et al, 2018, 2).…”

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“…[12,13] Similar to our results, Nabrdalik et al stated that compared to other antidiabetic medications, type 2 diabetes patients on metformin have an increased risk of experiencing gastrointestinal side effects including nausea, diarrhea, and stomach pain. [14] Furthermore, Sanchez-Rangel and Inzucchi reported that the most common side effects of metformin are gastrointestinal in nature including nausea, diarrhea, and abdominal discomfort. [15] The most often reported side effects of metformin, according to Rojas et al, were headaches, nausea, vomiting, diarrhea, and stomach pain.…”

Clinical Relevance of Gut Microbiota Alterations under the Influence of Selected Drugs—Updated Review

“…In addition, metformin interferes with the normal absorption of bile salts, which contributes to the exacerbation of discomfort and causes additional symptoms, such as loose stools [ 11 ]. A recent meta-analysis showed that using metformin, compared to other antidiabetic drugs, significantly elevates the risk of occurrence of gastrointestinal symptoms—among others, abdominal pain and diarrhoea—and there are some advantages to using an extended-release formulation [ 12 ]. The observed side-effects may be related to the effect of the drug on the microbiota [ 13 ].…”