Meta-analysis of Efficacy and Safety of Antidiabetics in Treating Gestational DM

Gestational Diabetes

Gestational diabetes mellitus (GDM) is a common complication that occurs during the second and third trimesters of pregnancy. The reported prevalence of GDM worldwide varies due to differences in diagnostic criteria. Nevertheless, it remains a fact that GDM increases the risk of other gestational complications for both the mother and the fetus. Understanding of GDM is continually deepening, and recent findings in this area form the basis for recommending stricter diagnostic criteria (IADPSG criteria – International Association of Diabetes and Pregnancy Study Groups) and management of blood glucose levels during pregnancy.¹ After GDM is diagnosed, women are advised to follow a diet and engage in physical activity, and if these methods do not control blood glucose levels, appropriate medications should be administered.

The authors of the presented meta-analysis² compared the efficacy and safety of metformin, glibenclamide, and insulin in the treatment of GDM by analyzing the results of subgroups of women diagnosed with GDM according to IADPSG criteria.

Analyzed Data

The analyzed sample of the studied population was derived from 29 studies found in the PubMed, Embase, and Web of Science databases with publication dates up to March 2022. Randomized controlled trials that included comparisons of outcomes of hypoglycemic agents use in women with GDM were included. For insulin, all forms suitable for use in pregnancy were included – human insulin, isophane, aspart, lispro, detemir, and glargine.

A probabilistic model – a Bayesian network (also known as a causal network or influence diagram) – was used for subsequent analysis.

Findings

The analysis estimated that metformin, compared to insulin, would lead to a slight improvement in overall weight gain during pregnancy (weighted mean difference [WMD] -1.24 kg; 95% confidence interval [CI] -2.38 to -0.09), but also an increased risk of not achieving the therapeutic goal (sensitivity analysis odds ratio [OR] 34.50; 95% CI 1.18–791.37).

The estimated effect of metformin further included an improvement in the birth weight of the newborn compared to insulin (WMD -102.58 g; 95% CI -180.45 to -25.49) and glibenclamide (WMD -137.84 g; 95% CI -255.31 to -25.45).

Administration of metformin appeared more advantageous in terms of the incidence of hypoglycemia within 1 hour of birth compared to insulin (OR 0.65; 95% CI 0.47–0.84) and glibenclamide (OR 0.41; 95% CI 0.26–0.66).

Conclusion and Discussion

Analysis using a probabilistic model – a Bayesian network – showed that among the glucose-lowering agents for women with GDM, metformin appears more beneficial in controlling overall weight gain during pregnancy, even compared to insulin, and birth weight, while glibenclamide seems to be associated with neonatal hypoglycemia. The authors of the study suggest conducting further randomized controlled trials focused on women with GDM diagnosed according to IADPSG criteria. In women with GDM who have insulin resistance and no contraindications to metformin, the benefits of metformin use extend beyond glycemic control, allowing avoidance of excessive weight gain during pregnancy for both the mother and the fetus.

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Sources:
1. American Diabetes Association Professional Practice Committee. Classification and diagnosis of diabetes: Standards of medical care in diabetes – 2022. Diabetes Care 2022; 45 (Suppl. 1): S17–S38, doi: 10.2337/dc22-S002.
2. Wang T., Jing Y., Guo H. et al. Efficacy and safety of hypoglycemic agents on gestational diabetes mellitus in women: a Bayesian network analysis of randomized controlled trials. Front Public Health 2022 Dec 2; 10: 980578, doi: 10.3389/fpubh.2022.980578.