Metformin, the aspirin of the 21st century: its role in gestational diabetes mellitus, prevention of preeclampsia and cancer, and the promotion of longevity.

https://tspace.library.utoronto.ca/bitstream/1807/106036/5/MiTy_Supplementary%20Appendix_TSpace.pdf

Metformin in women with type 2 diabetes in pregnancy (MiTy): a multicentre, international, randomised, placebo-controlled trial

Effects of selenium supplementation on glucose homeostasis, inflammation, and oxidative stress in gestational diabetes: Randomized, double-blind, placebo-controlled trial.

Aims. To assess the effect of metformin and to compare it with insulin treatment in patients with type 2 diabetes in pregnancy in terms of perinatal outcome, maternal complications, additional insulin requirement, and treatment acceptability. Methods. In this randomized, open label study, 206 patients with type 2 diabetes in pregnancy who met the eligibility criteria were selected from the antenatal clinics. Insulin was added to metformin treatment when required, to maintain the target glycemic control. The patients were followed up till delivery. Maternal, and perinatal outcomes and pharmacotherapeutic characteristics were recorded on a proforma. Results. Maternal characteristics were comparable in metformin and insulin treated group. 84.9% patients in metformin group required add-on insulin therapy at mean gestational age of 26.58 ± 3.85 weeks. Less maternal weight gain and pregnancy induced hypertension were observed in metformin treated group. Small for date babies were more in metformin group . Neonatal hypoglycemia was significantly less and so was NICU stay of >24 hours in metformin group . Significant reduction in cost of treatment was found in metformin group. Conclusion. Metformin alone or with add-on insulin is an effective and cheap treatment option for patients with type 2 diabetes in pregnancy. This trial is registered with clinical trial registration number: Clinical trials.gov NCT01855763 .

/pdf/metformin-treatment-in-type-2-diabetes-in-pregnancy-an-4ul3vtggzj.pdf

Metformin Treatment in Type 2 Diabetes in Pregnancy: An Active Controlled, Parallel-Group, Randomized, Open Label Study in Patients with Type 2 Diabetes in Pregnancy

Aim

To evaluate glycemic control among women with gestational diabetes mellitus (GDM) under insulin versus metformin (with or without insulin supplementation), and to identify metformin poor responders requiring supplemental insulin.



Methods

In Ain Shams University Hospital, mothers with 26–32-week GDM pregnancies, failing diet control, were randomized to receive metformin (n = 47) or insulin (n = 48). The primary outcome was glycemic control. Secondary outcomes included maternal weight, parameters predicting successful metformin monotherapy, neonatal hypoglycemia, and birthweight.



Results

Women using metformin (23.4% needing supplemental insulin) gained less weight (P 212 mg/dL and Wk1-mFG >95 mg/dL had a risk ratio of 58.6 (95%CI: 3.68–933.35, P = 0.004) and 11.5 (95%CI: 2.77–47.34,= 0.0008), respectively for needing supplemental insulin during the course of the study compared with women without.



Conclusion

Metformin is an effective and safe alternative to insulin in GDM. Women using metformin (± supplemental insulin) had similar glycemic control, less weight gain, and similar rates of side-effects as those on insulin monotherapy. Insulin supplementation to metformin therapy was more likely with elevated Hr1-GTT and Wk1-mFG.

Identification of metformin poor responders, requiring supplemental insulin, during randomization of metformin versus insulin for the control of gestational diabetes mellitus.

The aim of the present study is to assess the impact of adding oral metformin to insulin therapy in pregnant women with insulin-resistant diabetes mellitus. The current non-inferiority randomized controlled trial was conducted at Ain Shams University Maternity Hospital. The study included pregnant women with gestational or pre-existing diabetes mellitus at gestations between 20 and 34 weeks, who showed insulin resistance (defined as poor glycemic control at a daily dose of ≥1.12 units/kg). Recruited women were randomized into one of two groups: group I, including women who received oral metformin without increasing the insulin dose; and group II, including women who had their insulin dose increased. The primary outcome was maternal glycemic control. Secondary outcomes included maternal bouts of hypoglycemia, need for another hospital admission for uncontrolled diabetes during pregnancy, gestational age at delivery, mode of delivery, birth weight, birth trauma, congenital anomalies, 1- and 5-min Apgar score, neonatal hypoglycemia, need for neonatal intensive care unit (NICU) admission and adverse neonatal outcomes. A total number of 154 women with diabetes mellitus with pregnancy were approached; of them 90 women were eligible and were randomly allocated and included in the final analysis. The recruited 90 women were randomized into one of two groups: group I (metformin group) (n = 46), including women who received oral metformin in addition to the same initial insulin dose; and group II (control group) (n = 44), including women who had their insulin dose increased according to the standard protocol. The mean age of included women was 29.84 ± 5.37 years (range 20–42 years). The mean gestational age at recruitment was 28.7 ± 3.71 weeks (range 21–34 weeks). Among the 46 women of group I, 17 (36.9 %) women reached proper glycemic control at a daily metformin dose of 1,500 mg, 18 (39.2 %) at a daily dose of 2,000 mg, while 11 (23.9 %) received metformin at a daily dose of 2,000 mg without reaching proper glycemic control and needed raising the dose of insulin dose. Adding metformin to insulin therapy in women with insulin-resistant diabetes mellitus with pregnancy seems to be effective in proper glycemic control in a considerable proportion of women, along with benefits of reduced hospital stay, reduced frequency of maternal hypoglycemia as well as reduced frequency of neonatal hypoglycemia, NICU admission and neonatal respiratory distress syndrome.

The role of adding metformin in insulin-resistant diabetic pregnant women: a randomized controlled trial.

A cross sectional study was conducted for a sample of 45 anemic children and 15 healthy children (control group) in five primary health care centers in Hawija district in Kirkuk governorate. All children were between 6-60 months old. The study started from April 1 to August 31, 2021. Anemia was diagnosed by ferritin, Hb, RBCs, PCV, and WBCs tests. The role of gender and age in anemia was studied, and the results were as follows: The group of patient's

Estimation of Some Blood Parameters in Anemic Children Patients

This study aimed at assessing the correlations between gene expression of TNF-a, IFN-g, TGF-β in peripheral lymphocytes from women suffering from repeated implantation failure before and after intravenous Intra-lipid (IL) therapy, and correlation between changes in gene expression with IL infusion and success rate of IVF cycles. Twenty-three women complaining of unexplained infertility without history of autoimmune disorders, or immunodeficient diseases were included. All women included aged <40 years, BMI <28 with history of recurrent IVF cycles failure, seeking medical advice for new IVF trial. All were average responders to induction of ovulation (≥5 oocytes in each cycle) with good quality embryos transferred to uterus at proper time. Included women received 200 ml of 10% IL slowly intravenous. Two venous blood samples were taken from all candidates, one before IL infusion and the second was at day of embryo transfer. The current study detected a significant reduction of expression in TNF-a and increased expression of TGF-β, while non-significant reduction in expression of IFN-g after treatment. Significant associations between reduction of TNF-α, IFN-g expression and positive clinical and ongoing pregnancy were observed, while increased TGF-β expression was associated with only positive ongoing pregnancy. In conclusion, IL therapy might have a positive impact on IVF pregnancy rates via alterations in peripheral cytokines expression mainly reduction of TNF-a mRNA expression and increased TGF-b mRNA expression.

/pdf/correlation-of-tnf-a-ifn-g-and-tgf-b-expression-with-in-2032xl1o.pdf

Correlation of TNF-α, IFN-γ and TGF-β Expression with In-vitro Fertilization Success Rates in Women with Recurrent Implantation Failure Undergoing Treatment with Intra-lipid Infusion

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Papers

The role of adding metformin in insulin-resistant diabetic pregnant women: a randomized controlled trial.

Estimation of Some Blood Parameters in Anemic Children Patients

Correlation of TNF-α, IFN-γ and TGF-β Expression with In-vitro Fertilization Success Rates in Women with Recurrent Implantation Failure Undergoing Treatment with Intra-lipid Infusion