Metformin induces weight loss associated with gut microbiota alteration in non-diabetic obese women: a randomized double-blind clinical trial

in European Journal of Endocrinology
Correspondence should be addressed to A-R Soroush or J Raes; Email: soroush.journal@gmail.com or jeroen.raes@med.kuleuven.be

*(A-R Soroush and J Raes contributed equally to this work)

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Objective

The increasing prevalence of obesity over the past few decades constitutes a global health challenge. Pharmacological therapy is recommended to accompany life-style modification for obesity management. Here, we perform a clinical trial to investigate the effects of metformin on anthropometric indices and gut microbiota composition in non-diabetic, treatment-naive obese women with a low-calorie diet (LCD).

Design

Randomized double-blind parallel-group clinical trial

Methods

Forty-six obese women were randomly assigned to the metformin (500 mg/tab) or placebo groups using computer-generated random numbers. Subjects in both groups took two tablets per day for 2 months. Anthropometric measurements and collection of blood and fecal samples were done at the baseline and at the end of the trial. Gut microbiota composition was assessed using 16S rRNA amplicon sequencing.

Results

Twenty-four and twenty-two subjects were included in the metformin + LCD and placebo + LCD groups, respectively; at the end of trial, 20 and 16 subjects were analyzed. The metformin + LCD and placebo + LCD caused a 4.5 and 2.6% decrease in BMI from the baseline values, respectively (P < 0.01). Insulin concentration decreased in the metformin + LCD group (P = 0.046). The overall fecal microbiota composition and diversity were unaffected in the metformin + LCD group. However, a significant specific increase in Escherichia/Shigella abundance was observed after metformin + LCD intervention (P = 0.026). Fecal acetate concentration, but not producers, was significantly higher in the placebo + LCD group, adjusted for baseline values and BMI (P = 0.002).

Conclusions

Despite the weight reduction after metformin intake, the overall fecal microbiota composition remained largely unchanged in obese women, with exception of changes in specific proteobacterial groups.

 

     European Society of Endocrinology

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Figures

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    Flow diagram of study participants.

  • View in gallery

    Gut microbial diversity indices before and after (A) metformin (n = 20) or (B) placebo (n = 16) treatment in obese women. Color is indicative of time. A full colour version of this figure is available at https://doi.org/10.1530/EJE-18-0826.

  • View in gallery

    PCoA ordination of Bray–Curtis distances between samples before and after (A) metformin (n = 20) or (B) placebo (n = 16) treatment in obese women. Each data point represents an individual sample. Symbol is indicative of enterotypes and color is indicative of time. A full colour version of this figure is available at https://doi.org/10.1530/EJE-18-0826.

  • View in gallery

    Distribution of the gut microbiome enterotypes before and after (A) metformin (n = 20) or (B) placebo (n = 16) treatment in obese women. Color is indicative of enterotypes. A full colour version of this figure is available at https://doi.org/10.1530/EJE-18-0826.

  • View in gallery

    Changes in the relative abundance of fecal bacterial genus after metformin (n = 20) treatment in obese women. Color is indicative of time. *P < 0.05.

  • View in gallery

    Concentration of fecal short chain fatty acids (SCFAs) before and after metformin (n = 20) or placebo (n = 16) treatment in obese women. Color is indicative of time. (A) Acetate, (B) Propionate, (C) Butyrate.

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