Response to Letter in regards to Response to Article “Are There … – Dove Medical Press

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Back to Journals » Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy » Volume 15
Authors Dzięgielewska-Gęsiak S , Fatyga E, Piłot M, Wierzgoń A, Muc-Wierzgoń M 
Received 5 December 2022
Accepted for publication 13 December 2022
Published 21 December 2022 Volume 2022:15 Pages 3989—3991
DOI https://doi.org/10.2147/DMSO.S400278
Sylwia Dzięgielewska-Gęsiak,¹ Edyta Fatyga,¹ Magdalena Piłot,¹ Aleksander Wierzgoń,² Małgorzata Muc-Wierzgoń¹

¹Department of Internal Medicine Prevention, Medical University of Silesia in Katowice, Katowice, Poland; ²Department of Environmental Biotechnology, Faculty of Energy and Environmental Engineering, Silesian University of Technology, Gliwice, Poland

Correspondence: Sylwia Dzięgielewska-Gęsiak, Department of Internal Medicine Prevention, Medical University of Silesia in Katowice, 41-902 Bytom, Piekarska 18 St, Katowice, Poland, Tel/Fax +48/32/39-76-527, Email [email protected]

View the original paper by Dr Dzięgielewska-Gęsiak and colleagues
This is in response to the Letter to the Editor
Various patients with type 2 diabetes mellitus (T2DM) need alternative types of treatments. The mainstream strategy for T2DM treatment mainly includes the administration of oral hypoglycemic drugs and/or injectable agents like insulin secretagogues. In our research we investigated head-to-head gut microbiome in the T2DM patients with long duration of treatment by the most traditional type – metformin group or metformin+insulin group. Adding next oral hypoglycemic agents or insulin is intended to delay diabetic complications and improve outcomes. Study has revealed low richness and diversity of gut microbiota in those with long treatment with metformin or metformin+insulin with no differences between groups.
We have read the letter by Panjaitan et al regarding our article with interest and appreciate the criticisms and comments expressed. The letter brings the opportunity to further discuss the merits and limitations of our study. We respond to some doubts and questions. Moreover this leads us to propose international studies with a carefully selected group in the field of patients and drugs used so far and extending them to further hypoglycemic agents and various types of insulin in the area of gut microbiota investigation.
In response to Panjaitan et al, the aim of our study was to compare gut microbiome in type 2 diabetes mellitus (T2DM) patients using the most traditional strategy of treatment for the disease (metformin or metformin+insulin) for a long time (treatment duration 5–10 years).¹ The gut microbiome is mutable over time, depending on the health and disease, environment, diet and lifestyle, and, in those with disease, the used strategy of treatment (agents).²
In the meantime the novel therapeutic strategies for T2DM have been blooming, such as injectable drugs: glucagon-like peptide-1 (GLP-1) receptor agonists and/or oral hypoglycemic agents: sodium-dependent glucose transporter-2 (SGLT-2) inhibitors and dipeptidyl peptidase-4 (DPP-4) inhibitors. Still, we have also “old” antidiabetic drugs such as sulfonylureas, thiazolidinediones, and α-glucosidase inhibitors. In the introduction of our manuscript we mentioned pharmacomicrobiomics – the branch of medicine that investigates the interactions between the microbiome and drugs.³ All oral hypoglycemic agents and novel-like insulin secretagogues through different pathomechanisms may influence the gut microbiome – summarized in Table 1. Thus, we focused only on the metformin and metformin+insulin model of treatment. The investigation was carried out as a head-to-head study with comparison of two different types of treatment. We did not find any significant difference in the gut microbiome between the studied groups, neither in richness nor in diversity. At present, as we stated in the limitation of the study, due to the small number of patients, we cannot perform multiple regression analysis and answer why and how there were no differences of insulin influence on gut microbiome.⁴ In addition, we did not distinguish the type of insulin: long-acting, intermediate, short-acting, rapid-acting, mixed. Yet, it opens up new possibilities for further studies of the gut microbiome.

Table 1 Pathomechanisms Which through Oral Hypoglycemic Agents, Insulin and Novel-like Insulin Secretagouges Have Influence on the Gut Microbiome4,5

Table 1 Pathomechanisms Which through Oral Hypoglycemic Agents, Insulin and Novel-like Insulin Secretagouges Have Influence on the Gut Microbiome^4,5
Moreover we did not extend our study to the other T2DM treatment models, neither administered as oral hypoglycemic drugs nor as injectable agents like insulin secretagogues. It brings the opportunity to design novel models of the investigation by international teams.
Furthermore, we did not investigate the management of lifestyle and diet as these areas were unfortunately poorly documented and quantitated in the clinical data for that long time. Hopefully, study of the relationship between the age,sex, anthropometric measurements, comorbidities, diet, lifestyle and different administered antidiabetic drugs may be performed as multi-arm multi-stage clinical trial in the international group in the future.
Actually, all these T2DM patients must be managed using the established methods.
SDG and MMW went through the discussion letter and analyzed the data. SDG designed, answered, and wrote the original letter draft. EF, MP, and AW recommended required corrections, AW produced Table 1, and SDG and MMW carried out necessary revision for improvement of the manuscript accordingly.
The authors report no conflict of interest regarding this communication.
1. Dzięgielewska-Gęsiak S, Fatyga E, Piłot M, Wierzgoń A, Muc-Wierzgoń M. Are there differences in gut microbiome in patients with type 2 diabetes treated by metformin or metformin and insulin. Diabetes Metab Syndr Obes. 2022;15:3589–3599. doi:10.2147/DMSO.S377856
2. Iatcu CO, Steen A, Covasa M. Gut microbiota and complications of type-2 diabetes. Nutrients. 2021;14(1):166. doi:10.3390/nu14010166
3. Doestzada M, Vila AV, Zhernakova A, et al. Pharmacomicrobiomics: a novel route towards personalized medicine? Protein Cell. 2018;9(5):432‐445. doi:10.1007/s13238-018-0547-2
4. Chávez-Carbajal A, Pizano-Zárate ML, Hernández-Quiroz F, et al. Characterization of the gut microbiota of individuals at different T2D stages reveals a complex relationship with the host. Microorganisms. 2020;8(1):94. doi:10.3390/microorganisms8010094
5. Kyriachenko Y, Falalyeyeva T, Korotkyi O, Molochek N, Kobyliak N. Crosstalk between gut microbiota and antidiabetic drug action. World J Diabetes. 2019;10(3):154–168. doi:10.4239/wjd.v10.i3.154
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