Metformin has some advantages over insulin in relation to the changes in gut microbiota experienced during pregnancy
Experts from the Institute of Biomedical Research of Malaga (IBIMA Plataforma BIONAND), led by the Endocrinology and Nutrition FEA at the Hospital Costa del Sol, Andrea Fernández, and with the support and supervision of the group ‘Obesity, diabetes and its comorbidity: prevention and treatment’, led by the scientific director of IBIMA Plataforma BIONAND, Francisco J. Tinahones, have demonstrated the efficacy of oral administration of metformin to pregnant women for the treatment of gestational diabetes, constituting an effective alternative to insulin injections.
For years, clinical trials have been conducted with the aim of comparing the effect of metformin with insulin in gestational diabetes. It should be remembered that insulin, unlike metformin - at least in Spain, but not in other countries - is the first-line treatment for gestational diabetes. The MeDiGes clinical trial, the results of which were published in 2021, demonstrated the clinical benefits of metformin: mothers taking metformin gained less weight than those taking insulin, and had a lower rate of caesarean section.
The hypothesis, in this case, was that the clinical benefits of metformin already described in our population could be mediated by ‘improvements in oxidative stress parameters compared to insulin and healthy controls’, as pointed out by María Molina, researcher of the research line ‘genetic, epigenetic and environmental factors in the prevention, evolution and treatment of gestational diabetes’ together with doctors Sonsoles Morcillo and María José Picón, from the Hospital Universitario Virgen de la Victoria.
Two more specific parameters of oxidative stress (total antioxidant capacity and advanced protein oxidation products) and one of intestinal permeability (zonulin) were studied.
Following this investigation, oxidative stress parameters were found to increase in both metformin and insulin, but not in healthy controls, while intestinal permeability increased in both controls and insulin-treated patients, but did not increase in those treated with metformin.
The lack of increased intestinal permeability in the metformin group may be related to the beneficial changes in gut microbiota described above in our population of women with gestational diabetes compared to insulin.
During pregnancy there are often noticeable changes in a woman's body. At the metabolic level, glucose and lipid levels increase to facilitate the passage of nutrients to the baby. However, in predisposed women - for example, women who are obese or have a family history of diabetes - the body is unable to compensate for these changes, leading to the development of diabetes in pregnancy.
Object of study and research
The subject of this study included 120 women from August 2016 to February 2022. Among them, 34% received metformin (MET group), 32% received insulin (INS group) and 34% were healthy controls. Baseline and antenatal visits were performed at 25.4 ± 4.8 and 36.1 ± 0.8 weeks of pregnancy respectively. Advanced oxidation protein products (AOPP), total antioxidant capacity (TAC) and zonulin levels were measured at each visit.
On this last point, zonulin levels, from baseline to the antepartum visit, increased markedly in both healthy controls (0.6 ± 0.9 to 1.2 ± 1.7 ng/ml) and healthy controls (0.6 ± 0.9 to 1.2 ± 1.7 ng/ml), p = 0.004) as in the INS group (0.4 ± 0.3 to 0.6 ± 0.5 ng/ml, p = 0,034). However, they did not change in the MET group (0.4 ± 0.4 to 0.5 ± 0.4 ng/mL, p = 0,202). In contrast, TAC and AOPP levels were increased in women with GDM in both the INS and MET groups, but not in healthy controls.
Conclusion of the investigation
The study process, which has been published in the US National Library of Medicine (NIH), concludes that metformin has not been found to reduce oxidative stress parameters compared to insulin or control, but it does not increase intestinal permeability and ‘this non-increase may be related to the benefits on microbiota already described in this population with metformin compared to insulin’.
Tags diabetes • Diabetes Gestacional • Francisco J. Tinahones