ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2019) 63 P548 | DOI: 10.1530/endoabs.63.P548

Microbiota changes in type 2 diabetes patients intolerant to metformin after drug reintroduction

Araceli Muñoz-Garach1, Cristina María Díaz-Perdigones2, Isabel Moreno-Indias1,3, Maria Molina-Vega1, Isabel Cornejo-Pareja1 & Francisco J Tinahones1,3


1Universitary Hospital Virgen de la Victoria, Malaga, Spain; 2Vithas Xanit Hospital, Malaga, Spain; 3Instituto de Investigación Biomédica de Málaga (IBIMA), Malaga, Spain.


Introduction and objectives: Metformin (MTF) is the most used oral antidiabetic drug for the treatment of type 2 diabetes (T2D). However, intolerance to drug is frequent and limits its use. There are controversies about the cause of this problem, the gut microbiota has been proposed to be responsible. The gradual introduction of MTF could exercise an adaptation of gut microbiota that would facilitate tolerance to MTF. In this study we evaluate the metabolic changes and gut microbiota when introducing MTF in T2D patients with a history of intolerance.

Material and method: Prospective study, MTF 850 mg was introduced progressively (increasing doses every 2 weeks) to 40 patients. Those who tolerated the final dose were classified as tolerant. The subjects who presented digestive symptoms, to the introduction or dose progression, were classified as intolerant. Blood analysis and DNA extraction from faecal samples were made.

Results: Mean age 62.8±10.5 with 11.39±8.1 years of evolution of DM2. 70% of the patients were male. Diabetes complications: 15% microalbuminuria, 15% retinopathy and 5% neuropathy. Physical examination: weight 82.6±17.2 kg with BMI 32.2±6.7 kg/m2. Baseline analysis: Hb1Ac 7.38±0.9%, glucose 149.3±41.41 mg/dl, Cr 0.9±0.31 mg/dl, LDL 95±31 mg/dl, HDL 51±12.2 mg/dl, total cholesterol 180.9±39.8 mg/dl, triglycerides 175±98 mg/dl, microalbuminuria 60±160 mg/l. After the introduction 31.3% (n=10) were classified as tolerant to MTF. Nine samples of microbiota extracted at the end of the study were sequenced; five tolerant and four intolerant. We analysed the proportion of phyla, biodiversity and homogeneity of the samples with Shannon and Pielou indices.

Proportion phyla (n=9)Tolerants (n=5) Mean±S.D.Intolerants (n=4) Mean±S.D.Kruskal-wallis test P value
Actinobacteria14.4725±24.432.628±2.4950.6
Bacteroidetes36,2625±9.6147.364±7.790.086
Cyanobacteria0.08754±0.0980.092 ±0.1420.53
Firmicutes37,4375±1700537.64±9.021
Fusobacteria0.0950±0.190.00±0.000.26
Lentisphaerae0.0075±0.009570.04±0.0580.78
TM70.00±0.000.00±0.001
Tenericutes0.025±0.330.032±0.0560.89
Verrucomicrobia0.00±0.000.05±0.070.18
Proteobacteria23.25±22.912.01±7.10.62
Others0.5±0.8950.13±0.150.9

Conclusions: No differences were seen in intestinal microbiota profiles at the phyla level among patients tolerant and intolerant to MTF after the reintroduction of the drug. The small sample size could limit our results. The remaining samples are being analyzed to clarify possible changes in the main phyla.

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