Metformin Intolerance: A Proposal for Definition Using the GSRS

Paul Bouter; Oscar Natan

doi:doi:10.11648/j.ajcem.20221002.12

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Metformin Intolerance: A Proposal for Definition Using the GSRS

Paul Bouter, Oscar Natan

Published in American Journal of Clinical and Experimental Medicine (Volume 10, Issue 2)

Received: 1 March 2022 Accepted: 26 March 2022 Published: 9 April 2022

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Abstract

Metformin is a first line drug for the treatment of patients with type 2 diabetes mellitus (T2DM) and has been associated with metformin intolerance with disappointing patient adherence. Since there is no official definition for metformin intolerance, comparison of international study results on gastrointestinal complaints is almost impossible. In the present study with type 2 diabetes patients who are on a metformin immediate-release (MIR) and are visiting the outpatient’s department of internal medicine. To create a quantifiable and standardized definition of metformin intolerance, this study used the Gastro-intestinal Symptom Rating Scale (GSRS) to evaluate the gastrointestinal complaints. A total of 59 patients (mean age 62.56; +/- 12.08) completed the GSRS in an interview with a skilled investigator. The mean GSRS score for the study population was 34.56 (+/- 14.57). Subsequently two subpopulations were created using 50 as a cutoff point. This resulted in two populations with statistically significant different GSRS scores of 55.50 (+/- 7.88) for patients with a GSRS score of ≥ 50 versus 28.04 (+/- 8.86) for patients with a GSRS score of < 50. The total GSRS results for the various metformin dosages yielded comparable results (figure 1, p<0.05). The authors recommend the use of the GSRS in all studies on the topic of metformin intolerance to enable the comparison of results of international studies. In addition, the authors propose the use of a cutoff GSRS score of 50 as an international definition for metformin intolerance.

Published in	American Journal of Clinical and Experimental Medicine (Volume 10, Issue 2)
DOI	10.11648/j.ajcem.20221002.12
Page(s)	59-62
Creative Commons	This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.
Copyright	Copyright © The Author(s), 2022. Published by Science Publishing Group

Keywords

Metformin Intolerance, Metformin Immediate-release (MIR), Type 2 Diabetes Mellitus (T2DM), Gastrointestinal Symptom Rating Scale (GSRS)

References

[1]	Ogurtsova K, da Rocha Fernandes J. D, Huang H, et al. IDF Diabetes Atlas: Global estimates for the prevalence of diabetes for 2015 and 2040. 2017, Diabetes Research and Clinical Practice. 2017; 125: 40-50.
[2]	Gout-Zwart J. J, de Jong L. A, Saptenno L et al. Budget Impact Analysis of Metformin Sustained Release for the Treatment of Type 2 Diabetes in The Netherlands. Pharmacoecon Open. 2020; 4 (2): 321-330.
[3]	Inzucchi SI, Bergenstal RM, Buse JB et al 215. Management of hyperglycaemia in type 2 diabetes: a patient-centered approach. Update to a position statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetologia 2015; 58: 429-442.
[4]	Dandona P, Fonseca V, Mier A et al. Diarrhea and metformin in a diabetic clinic. Diabetes Care. 1983; 6 (5): 472-474.
[5]	UK Prospective Diabetes Study (UKPDS) Group. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes Lancet 1998; 352: 854-865.
[6]	Kahn S. E, Haffner S. M, Heise M. A et al. Glycaemic durability of rosiglitazone, metformin, or glyburide monotherapy. New England Journal of Medicine 2006; 355: 2427-2443.
[7]	Florez H, Luo J, Castillo-Florez S et al. Impact of metformin-induced gastro-intestinal symptoms on quality of life and adherence in patients with type 2 diabetes. Postgraduade Medicine, 2010; 122: 112-120.
[8]	De Jong L, Harmark L, Van Puijenbroek E, et al. Time course, outcome and management of adverse drug reactions associated with metformin from patient’s perspective: a prospective, observational cohort study in the Netherlands. 2016, European Journal of Clinical Pharmacology, 2016; 72 (5): 615-622.
[9]	Plat A, Penning-van Beest F, Kessabi S, Groot M, et al. Change of initial oral antidiabetic therapy in type 2 diabetic patients. Pharmacy World and Science 2009; 31 (6): 622-626.
[10]	Revicki DA, Wood M, Wiklund I, Crawley J. Reliability and validity of the gastrointestinal symptom rating scale in patients with gastroesophageal reflux disease. Qual Life Res. 1998; 7: 75-83.
[11]	Dujic T, Zhou K, Donnelly LA, Roger Tavendale R, Palmer CNA, Pearson ER. Association of Organic Cation Transporter 1 With Intolerance to Metformin in Type 2 Diabetes: A GoDARTS Study. Diabetes. 2015; 64 (5): 1786–1793.
[12]	Elbere I,, Kalnina I, Silamikelis I, Konrade I, Zaharenko L. Association of metformin administration with gut microbiome dysbiosis in healthy volunteers. PLoS One. 2018; 13 (9): e0204317.
[13]	Guo L, Guo X, Li Y et al. Effects of body mass index or dosage on gastrointestinal disorders associated with extended release metformin in type 2 diabetes: Sub-analysis of a Phase IV open-label trial in Chinese patients. Diabetes Metab Syndr 2016; 10 (3): 137-142.
[14]	McCreight LJ, Tore B, Connelly P, et al. Pharmacokinetics of metformin in patients with gastrointestinal intolerance. 2018, Diabetes, Obesity and Metabolism, pp. 20: 1593-1601.
[15]	Bonnet F, Scheen A. Understanding and overcoming metformin gastro-intestinal intolerance. Diabetes Obes Metab. 2017; 19 (4): 473-481.
[16]	Halmos EP, Power VA, Shepherd SJ. A et al. diet low in FODMAPs reduces symptoms of irritable bowel syndrome. Gastroenterology 2014; 146: 67-75.
[17]	Kistler BM, Biruete A, Chapman-Novakofski K et al. The relationship between intradialytic nutrition and gastrointestinal symptoms using a modified version of the Gastrointestinal Symptom Rating Scale. J Ren Nutr 2018; 2: 129-134.
[18]	Turan N, Astia TA, Kaya N. Reliability and validity of the Turkish version of the Gastrointestinal Symptom Rating Scale. Gastroenterol Nurs 2017; 40 (1): 47-55.
[19]	Souza GS, Hoffmann FA, Giuntini EB et al. Translation and validation of the Brazilian Portuguese version of the Gastrointestinal Symptom Rating Scale (GSRS) questionnaire. Arq Gastroenterol 2016; 53 (3): 146-51.

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APA Style

Paul Bouter, Oscar Natan. (2022). Metformin Intolerance: A Proposal for Definition Using the GSRS. American Journal of Clinical and Experimental Medicine, 10(2), 59-62. https://doi.org/10.11648/j.ajcem.20221002.12

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ACS Style

Paul Bouter; Oscar Natan. Metformin Intolerance: A Proposal for Definition Using the GSRS. Am. J. Clin. Exp. Med. 2022, 10(2), 59-62. doi: 10.11648/j.ajcem.20221002.12

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AMA Style

Paul Bouter, Oscar Natan. Metformin Intolerance: A Proposal for Definition Using the GSRS. Am J Clin Exp Med. 2022;10(2):59-62. doi: 10.11648/j.ajcem.20221002.12

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@article{10.11648/j.ajcem.20221002.12,
  author = {Paul Bouter and Oscar Natan},
  title = {Metformin Intolerance: A Proposal for Definition Using the GSRS},
  journal = {American Journal of Clinical and Experimental Medicine},
  volume = {10},
  number = {2},
  pages = {59-62},
  doi = {10.11648/j.ajcem.20221002.12},
  url = {https://doi.org/10.11648/j.ajcem.20221002.12},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ajcem.20221002.12},
  abstract = {Metformin is a first line drug for the treatment of patients with type 2 diabetes mellitus (T2DM) and has been associated with metformin intolerance with disappointing patient adherence. Since there is no official definition for metformin intolerance, comparison of international study results on gastrointestinal complaints is almost impossible. In the present study with type 2 diabetes patients who are on a metformin immediate-release (MIR) and are visiting the outpatient’s department of internal medicine. To create a quantifiable and standardized definition of metformin intolerance, this study used the Gastro-intestinal Symptom Rating Scale (GSRS) to evaluate the gastrointestinal complaints. A total of 59 patients (mean age 62.56; +/- 12.08) completed the GSRS in an interview with a skilled investigator. The mean GSRS score for the study population was 34.56 (+/- 14.57). Subsequently two subpopulations were created using 50 as a cutoff point. This resulted in two populations with statistically significant different GSRS scores of 55.50 (+/- 7.88) for patients with a GSRS score of ≥ 50 versus 28.04 (+/- 8.86) for patients with a GSRS score of < 50. The total GSRS results for the various metformin dosages yielded comparable results (figure 1, p<0.05). The authors recommend the use of the GSRS in all studies on the topic of metformin intolerance to enable the comparison of results of international studies. In addition, the authors propose the use of a cutoff GSRS score of 50 as an international definition for metformin intolerance.},
 year = {2022}
}

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TY - JOUR
T1 - Metformin Intolerance: A Proposal for Definition Using the GSRS
AU - Paul Bouter
AU - Oscar Natan
Y1 - 2022/04/09
PY - 2022
N1 - https://doi.org/10.11648/j.ajcem.20221002.12
DO - 10.11648/j.ajcem.20221002.12
T2 - American Journal of Clinical and Experimental Medicine
JF - American Journal of Clinical and Experimental Medicine
JO - American Journal of Clinical and Experimental Medicine
SP - 59
EP - 62
PB - Science Publishing Group
SN - 2330-8133
UR - https://doi.org/10.11648/j.ajcem.20221002.12
AB - Metformin is a first line drug for the treatment of patients with type 2 diabetes mellitus (T2DM) and has been associated with metformin intolerance with disappointing patient adherence. Since there is no official definition for metformin intolerance, comparison of international study results on gastrointestinal complaints is almost impossible. In the present study with type 2 diabetes patients who are on a metformin immediate-release (MIR) and are visiting the outpatient’s department of internal medicine. To create a quantifiable and standardized definition of metformin intolerance, this study used the Gastro-intestinal Symptom Rating Scale (GSRS) to evaluate the gastrointestinal complaints. A total of 59 patients (mean age 62.56; +/- 12.08) completed the GSRS in an interview with a skilled investigator. The mean GSRS score for the study population was 34.56 (+/- 14.57). Subsequently two subpopulations were created using 50 as a cutoff point. This resulted in two populations with statistically significant different GSRS scores of 55.50 (+/- 7.88) for patients with a GSRS score of ≥ 50 versus 28.04 (+/- 8.86) for patients with a GSRS score of < 50. The total GSRS results for the various metformin dosages yielded comparable results (figure 1, p<0.05). The authors recommend the use of the GSRS in all studies on the topic of metformin intolerance to enable the comparison of results of international studies. In addition, the authors propose the use of a cutoff GSRS score of 50 as an international definition for metformin intolerance.
VL - 10
IS - 2
ER -

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Author Information

Paul Bouter

Department of Internal Medicine, Jeroen Bosch Hospital, Den Bosch, The Netherlands
Oscar Natan

Department of Internal Medicine, Jeroen Bosch Hospital, Den Bosch, The Netherlands

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APA Style

Paul Bouter, Oscar Natan. (2022). Metformin Intolerance: A Proposal for Definition Using the GSRS. American Journal of Clinical and Experimental Medicine, 10(2), 59-62. https://doi.org/10.11648/j.ajcem.20221002.12

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ACS Style

Paul Bouter; Oscar Natan. Metformin Intolerance: A Proposal for Definition Using the GSRS. Am. J. Clin. Exp. Med. 2022, 10(2), 59-62. doi: 10.11648/j.ajcem.20221002.12

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AMA Style

Paul Bouter, Oscar Natan. Metformin Intolerance: A Proposal for Definition Using the GSRS. Am J Clin Exp Med. 2022;10(2):59-62. doi: 10.11648/j.ajcem.20221002.12

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@article{10.11648/j.ajcem.20221002.12,
  author = {Paul Bouter and Oscar Natan},
  title = {Metformin Intolerance: A Proposal for Definition Using the GSRS},
  journal = {American Journal of Clinical and Experimental Medicine},
  volume = {10},
  number = {2},
  pages = {59-62},
  doi = {10.11648/j.ajcem.20221002.12},
  url = {https://doi.org/10.11648/j.ajcem.20221002.12},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ajcem.20221002.12},
  abstract = {Metformin is a first line drug for the treatment of patients with type 2 diabetes mellitus (T2DM) and has been associated with metformin intolerance with disappointing patient adherence. Since there is no official definition for metformin intolerance, comparison of international study results on gastrointestinal complaints is almost impossible. In the present study with type 2 diabetes patients who are on a metformin immediate-release (MIR) and are visiting the outpatient’s department of internal medicine. To create a quantifiable and standardized definition of metformin intolerance, this study used the Gastro-intestinal Symptom Rating Scale (GSRS) to evaluate the gastrointestinal complaints. A total of 59 patients (mean age 62.56; +/- 12.08) completed the GSRS in an interview with a skilled investigator. The mean GSRS score for the study population was 34.56 (+/- 14.57). Subsequently two subpopulations were created using 50 as a cutoff point. This resulted in two populations with statistically significant different GSRS scores of 55.50 (+/- 7.88) for patients with a GSRS score of ≥ 50 versus 28.04 (+/- 8.86) for patients with a GSRS score of < 50. The total GSRS results for the various metformin dosages yielded comparable results (figure 1, p<0.05). The authors recommend the use of the GSRS in all studies on the topic of metformin intolerance to enable the comparison of results of international studies. In addition, the authors propose the use of a cutoff GSRS score of 50 as an international definition for metformin intolerance.},
 year = {2022}
}

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