Metformin use in gestational diabetes mellitus and neonatal outcomes: a systematic review and meta-analysis on the risk of small for gestational age

Purpose: It remains unclear whether maternal metformin use in gestational diabetes mellitus (GDM) is associated with an increased risk of small-for-gestational-age (SGA) newborns.

Methods and results: A systematic literature search was conducted across PubMed, Embase, and the Cochrane Library up to September 1, 2024. Nineteen studies (n = 115,192 participants), comprising randomized controlled trials and cohort studies, were included. Two evaluators independently assessed eligibility and bias risk. Maternal use of metformin for GDM was not significantly associated with SGA incidence in newborns (OR = 1.10, 95% CI: 0.97–1.24, p = 0.14). No notable differences were observed compared to insulin-treated (n = 27,622, OR = 1.25, 95% CI: 0.91–1.73, p = 0.17) or placebo groups (n = 1,685, OR = 1.36, 95% CI: 0.80–2.32, p = 0.26). However, two studies (n = 554) indicated a lower SGA incidence with metformin than with diet modification therapy (OR = 0.50, 95% CI: 0.29–0.87, p = 0.01).

Conclusions: Maternal metformin use in the management of GDM doesn't increase SGA risk in offspring, suggesting its relative safety and effectiveness in this context. Further research is required to explore metformin's long-term effects of metformin on offspring of mothers with GDM.

Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/view/CRD420251141984, identifier CRD420251141984.

Introduction

Gestational diabetes mellitus (GDM), defined as glucose intolerance with onset or first recognition during pregnancy, is now recognized as one of the most prevalent pregnancy-related complications worldwide (1, 2). GDM can increase the risk of perinatal complications and adversely affect long-term metabolic health in both mothers and their offspring. Metabolic diseases pose a serious threat to human health and have become a major global public health issue (3). Therefore, effective management of blood glucose levels in mothers with GDM is essential to prevent intergenerational transmission of metabolic diseases. There are a variety of clinical treatments for GDM, including dietary modifications, increased physical activities, oral hypoglycemic drugs, and other pharmacological therapies (4, 5). Among these, metformin is widely used due to its efficacy, safety, and low cost. As a first-line therapy, metformin has many advantages, including improvements in hemoglobin A1C (HbA1c), weight, and cardiovascular outcomes. Unless contraindicated, metformin is considered an initial pharmacological option for managing diabetes (6, 7). With the rising prevalence of GDM, the use of metformin during pregnancy has become increasingly common. However, recent evidence suggests that metformin crosses the placenta through passive diffusion, potentially reaching fetal concentrations equal to or exceeding maternal levels, thereby leading to concerns about potential effects on fetal and placental growth (8, 9). Animal studies have indicated that fetal accumulation of metformin is linked to growth restriction, as seen the emergence of SGA in the offspring of primates exposed to the drug within 30 days after conception (10). In human studies, the association between maternal metformin use and small-for-gestational-age (SGA) infants, defined as birth weight below the 10th percentile for gestational age, remains poorly characterized. Current evidence is conflicting, with some studies suggesting an increased risk of SGA (11), while others report no significant association (10). This inconsistency may stem from heterogeneity across study populations, diagnostic criteria, and treatment protocols. Furthermore, the mechanisms underlying potential effects of metformin on fetal growth require further elucidation. Given these uncertainties, it is necessary to systematically evaluate the evidence regarding the effects of metformin on fetal growth outcomes. Therefore, we conducted a meta-analysis to assess the association between maternal metformin use during pregnancy and SGA risk in offspring. The findings of this study will provide evidence-based recommendations to help optimize clinical decision-making in the management of GDM and reduce adverse neonatal outcomes.

Methods

Literature searches, search strategies, and eligibility

A systematic literature search was performed using predefined search terms in PubMed (June 1997 to September 1, 2024), Embase (1974 to September 1, 2024), and the Cochrane Library (from inception to September 1, 2024). No filters were applied, language or location restrictions were applied.

In the included studies, the diagnosis of GDM was based on the diagnostic criteria of the respective local medical centers where each study was conducted. We did not exclude literature based on differences in GDM diagnostic criteria. Conference abstracts were eligible only if they provided sufficient data for evaluation, no abstracts met this criterion and thus were excluded.

Document screening and data extraction

Data extraction and quality assessment were conducted independently by two reviewers. Disagreements were resolved by consensus or by consulting a third reviewer. The search terms included: Metformin-related terms: (1) Metformin OR Dimethylbiguanidine OR Dimethylguanylguanidine OR Glucophage; (2) Hydrochloride OR Hydrochloride, Metformin OR Metformin HCl OR HCl, Metformin. Infant-related terms: Infant, Small for Gestational Age OR Infant, Low Birth Weight OR Infant, Premature OR SGA; (3) Birth-related terms: Birth Weight OR Infant, Newborn. An initial screening of titles and abstracts was conducted, followed by a comprehensive review of full texts. The results of each stage of the review process were summarized in the flowchart (Figure 1). Additionally, details of the search strategy details were shown in Figure 2.

Figure 1

Figure 1. Flow diagram of studies identified in the systematic review. This flowchart summarizes the process of evidence search and study selection for this meta-analysis, including the inclusion and exclusion criteria applied at each stage. The analysis focuses on the relationship between metformin use and small for gestational age (SGA) (defined as birth weight below the 10th percentile for gestational age).

Figure 2

Figure 2. Screenshot of the search interface displaying keywords and databases used (PubMed, Embase, Cochrane Library) in the systematic search for studies on metformin, GDM, and SGA.

Risk of bias assessment

Risk of bias assessments reporting overall quality of included studies are presented in Figure 3. RCTs' risk of bias was evaluated collaboratively using the Cochrane Collaboration tool, which assessed seven domains (selection, performance, detection, attrition, reporting, and other biases) for each study and rated as low, unclear, or high risk (Figure 3). For each comparison, the level of certainty of the evidence ranged from low to high. The Newcastle-Ottawa Scale (NOS), which evaluates eight domains of bias, was applied to assess observational studies. The median Newcastle-Ottawa score for the 19 studies reviewed was 7, with quality scores ranging from 6 to 8 for cohort studies and consistently at 7 for case-control studies. Based on these evaluations, all studies were considered high quality (Table 1). The primary outcome measure was the unadjusted odds ratio (OR) for binary outcomes. Meta-analysis was conducted using Review Manager (RevMan) version 5.4. Funnel plots were generated to assess publication bias in datasets with more than nine trials comparing the metformin group to the unclassified population or the insulin group (Figures 4, 5). Heterogeneity was quantified using the I² statistic to identify variability due to non-random factors.

Figure 3

Figure 3. Risk of bias summary in Cochrane literature quality evaluation.

Table 1

Table 1. The bias of the observational studies.

Figure 4

Figure 4. Funnel plot assessing publication bias for studies comparing metformin use and SGA incidence in the overall unclassified population.

Figure 5

Figure 5. Funnel plot assessing publication bias for studies comparing metformin use and SGA incidence specifically in studies using insulin as comparator.

Results

Study and quality characteristics

Our search identified 1,069 records. After removing duplicates and screening titles, abstracts, and full texts, 19 studies involving 115,192 pregnancies were included (Figure 1). These studies included 19 couples of the experimental and control group. Of all the included studies, 50% were randomized controlled trials (RCTs). Table 2 provides an overview of the study designs and outcomes of the included studies. Notably, approximately 45% of the studies did not report data on race or ethnicity, which could potentially limit the generalizability of the results.

Table 2

Table 2. Classification the included articles.

Neonatal outcomes

The association between maternal metformin use and the risk of SGA was evaluated across four comparator groups. The pooled analysis results are summarized in Table 3: No significant difference: Metformin vs. Unclassified Population (n = 115,192) (OR 1.10, 95% CI 0.97–1.24, p = 0.14, I² = 39%) (Figure 6) (12–31), Metformin vs. Insulin (n = 27,622) (OR 1.25, 95% CI 0.91–1.73, I² = 54%) (Figure 7) (12, 14, 17–20, 22–25, 29, 30), Metformin vs. Placebo (n = 1,685) (OR 1.36, 95% CI 0.80–2.32, I² = 55%) (Figure 8) (16, 21, 31). Metformin vs. Diet Modification (n = 554): The risk of SGA was significantly lower in the metformin group (OR 0.50, 95% CI 0.29–0.87, I² = 0%) (Figure 9) (13, 28).

Table 3

Table 3. Meta-analysis of SGA risk: metformin vs. different comparators.

Figure 6

Figure 6. Studies evaluating the risk of SGA comparing metformin vs. unclassified population.

Figure 7

Figure 7. Studies evaluating the risk of SGA comparing metformin vs. insulin.

Figure 8

Figure 8. Studies evaluating the risk of SGA comparing metformin vs. placebo.

Figure 9

Figure 9. Studies evaluating the risk of SGA comparing metformin vs. diet modification.

Discussion

This meta-analysis, encompassing data from 115,192 pregnancies across 19 studies, provides the most comprehensive evidence to date regarding the association between metformin use for GDM and the risk of SGA. The principal finding is that metformin does not significantly increase the risk of SGA compared to insulin, placebo, or an unclassified treatment population.

The comparable SGA risk between metformin and insulin aligns with a previous meta-analysis, reinforcing the reliability of this finding (32). Although some individual studies mentioned a potential increased risk of SGA with maternal metformin use, our statistical analysis did not support this concern. The reason might be that metformin improves maternal insulin sensitivity without substantially impairing placental function, thus exerting minimal adverse effects on fetal growth. However, as metformin crosses the placenta, the long-term effects on fetal growth and metabolism remain unclear, necessitating further study (8, 9).

A noteworthy finding is the significantly lower risk of SGA observed with metformin compared to diet modification alone (OR 0.50). This contrasts with the null findings in other comparisons and has not been highlighted in prior reviews.

This finding highlights the potential limitations of dietary interventions in achieving optimal glycemic control during pregnancy. This conclusion is based on limited data, as studies comparing metformin with diet are few and methodologically heterogeneous, warranting cautious interpretation (13, 28).

By incorporating a larger number of studies than previous reviews, this analysis provides a more comprehensive assessment of the association between metformin use and SGA risk. In the process of searching, we used the keywords with metformin, SGA, GDM and the synonymous substitutions, to assure more and complete articles being included.

A major strength of this study was the comprehensive analysis of multiple comparative groups. No previous meta-analysis has specifically compared metformin with multiple alternative treatments regarding SGA incidence, highlighting the unique contribution of our study. Conversely, insulin therapy should remain the preferred option in high-risk populations, including those with pre-existing fetal growth concerns or contraindications to metformin use.

However, there were several limitations. Variations in GDM diagnostic criteria, treatment protocols, metformin dosing (ranging from 500 mg to 2500 mg daily), patient baseline characteristics (e.g., age, BMI, ethnicity—with approximately 45% of studies not reporting ethnicity) contributed to the moderate-to-high statistical heterogeneity observed (I² up to 55%) (9, 33) (Table 4). It suggests that the overall “no significant difference” finding may mask variable effects in different patient subgroups or clinical settings. Additionally, the complete absence of long-term follow-up data in the included studies represents a major evidence gap. While our analysis focused on neonatal SGA, it provides no information on potential long-term developmental, metabolic, or cardiovascular outcomes in children exposed to metformin in utero. Therefore, the absence of an overall significant association should not be interpreted as uniform safety across all clinical contexts, and individualized treatment decisions remain essential. This limitation precludes a comprehensive safety assessment and means that current clinical recommendations based on short-term neonatal outcomes must be made with caution, acknowledging this unknown. In clinical practice, this means that while metformin may be appropriate for many women with GDM, insulin may remain preferable in pregnancies with existing concerns about fetal growth or in populations not well represented in current studies. The limitations weaken the robustness and generalizability of these specific comparisons, and prevents a comprehensive evaluation of the potential developmental and metabolic effects of prenatal metformin exposure on offspring, preventing a definitive evaluation of metformin's long-term safety profile.

Table 4

Table 4. The table summarizing study characteristics and sources of heterogeneity.

To address the limitations of current evidence and translate these findings into clearer clinical guidance, future research should prioritize the following: Standardization of Study Protocols: prospective studies, especially randomized controlled trials, should adopt consensus-based, standardized protocols for GDM diagnosis, metformin dosing, and comparator treatments. This will reduce methodological heterogeneity and facilitate more robust and comparable meta-analyses in the future. Long-term Offspring Follow-up: the focus of research must extend beyond birth outcomes. Large-scale, longitudinal cohort studies are imperative to evaluate the long-term cardiometabolic health, neurodevelopment, and growth trajectories of children exposed to metformin in utero. Such data are essential for a comprehensive risk-benefit assessment of metformin use in pregnancy.

Overall, maternal oral metformin can indeed reduce newborn weight to a certain extent (metformin can prevent LGA to a certain extent), but the data tend to presents a milder effect that has not reached the level of SGA. The potential for its broader clinical application remains promising. Some studies provided proof of concept that treatment of preterm pre-eclampsia and pregnancy-related hypertension is possible (34, 35). Mechanistic studies exploring how metformin influences placental function and fetal development may further elucidate its safety profile. Through this analysis, we currently agree on the safety of metformin, it is reasonable to use metformin in those with type 2 diabetes and chronic hypertension or nephropathy in pregnancy (36).

Conclusion

This meta-analysis suggests that metformin is a cost-effective and generally safe treatment option for GDM, with no significant association with increased SGA risk in the general population. Metformin presents a practical alternative for patients who cannot tolerate insulin or face significant financial constraints. Its affordability and ease of use make it an attractive option for low-risk pregnancies or resource-limited settings. Despite these promising findings, the need for further research remains critical to fully understand the long-term effects of metformin and to optimize GDM management strategies. A patient-centered approach that considers individual risk factors, treatment preferences, and socioeconomic circumstances is crucial for tailoring GDM management strategies (6, 8, 9, 36, 37).

Data availability statement

The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding authors.

Author contributions

WZhang: Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Supervision, Validation, Visualization, Writing – original draft. LR: Conceptualization, Formal analysis, Investigation, Methodology, Supervision, Validation, Visualization, Writing – review & editing. JD: Conceptualization, Project administration, Resources, Supervision, Validation, Visualization, Writing – review & editing. RS: Conceptualization, Investigation, Methodology, Project administration, Software, Supervision, Validation, Visualization, Writing – review & editing. WZhao: Conceptualization, Methodology, Project administration, Software, Validation, Visualization, Writing – review & editing. XS: Conceptualization, Methodology, Project administration, Software, Validation, Visualization, Writing – review & editing. SJ: Methodology, Supervision, Validation, Visualization, Writing – review & editing. ZW: Conceptualization, Funding acquisition, Project administration, Supervision, Validation, Visualization, Writing – review & editing. WW: Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Project administration, Resources, Supervision, Validation, Visualization, Writing – review & editing.

Funding

The author(s) declared that financial support was received for this work and/or its publication. This work was supported by the Natural Science Foundation of Shandong Province [grant numbers ZR2024QH624], the Major Scientific and Technological Innovation Project (MSTIP) [grant numbers 2023CXGC010705] and Shandong Province Pig Industry Technology System [grant numbers SDAIT-08-17].

Acknowledgments

Thanks for the supports by grants from the Natural Science Foundation of Shandong Province (ZR2024QH624), the Major Scientific and Technological Innovation Project (MSTIP) (2023CXGC010705) and Shandong Province Pig Industry Technology System (SDAIT-08-17).

Conflict of interest

The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Generative AI statement

The author(s) declared that generative AI was not used in the creation of this manuscript.

Any alternative text (alt text) provided alongside figures in this article has been generated by Frontiers with the support of artificial intelligence and reasonable efforts have been made to ensure accuracy, including review by the authors wherever possible. If you identify any issues, please contact us.

Publisher's note

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

Abbreviations

GDM, gestational diabetes mellitus; SGA, small for gestational age; OR, odds ratio; RCT, randomized controlled trials.

References

1. Sweeting A, Wong J, Murphy HR, Ross GP. A clinical update on gestational diabetes mellitus. Endocr Rev. (2022) 43:763–93. doi: 10.1210/endrev/bnac003

PubMed Abstract | Crossref Full Text | Google Scholar

2. Moon JH, Jang HC. Gestational diabetes mellitus: diagnostic approaches and maternal-offspring complications. Diabetes Metab J. (2022) 46:3–14. doi: 10.4093/dmj.2021.0335

PubMed Abstract | Crossref Full Text | Google Scholar

3. Sun H, Saeedi P, Karuranga S, Pinkepank M, Ogurtsova K, Duncan BB, et al. IDF diabetes atlas: global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045. Diabetes Res Clin Pract. (2022) 183:109119. doi: 10.1016/j.diabres.2021.109119

PubMed Abstract | Crossref Full Text | Google Scholar

4. Lende M, Rijhsinghani A. Gestational diabetes: overview with emphasis on medical management. Int J Environ Res Public Health. (2020). 17:9573. doi: 10.3390/ijerph17249573

PubMed Abstract | Crossref Full Text | Google Scholar

5. Modzelewski R, Stefanowicz-Rutkowska MM, Matuszewski W, Bandurska-Stankiewicz EM. Gestational diabetes mellitus-recent literature review. J Clin Med. (2022) 11:5736. doi: 10.3390/jcm11195736

PubMed Abstract | Crossref Full Text | Google Scholar

6. Maruthur NM, Tseng E, Hutfless S, Wilson LM, Suarez-Cuervo C, Berger Z, et al. Diabetes medications as monotherapy or metformin-based combination therapy for type 2 diabetes: a systematic review and meta-analysis. Ann Intern Med. (2016) 164:740–51. doi: 10.7326/M15-2650

PubMed Abstract | Crossref Full Text | Google Scholar

7. American Diabetes Association Professional Practice Committee. Pharmacologic approaches to glycemic treatment: standards of care in diabetes-2024. Diabetes Care. (2024) 47(Suppl 1):S158–78. doi: 10.2337/dc24-S009

Crossref Full Text | Google Scholar

8. Romero R, Erez O, Hüttemann M, Maymon E, Panaitescu B, Conde-Agudelo A, et al. Metformin, the aspirin of the 21st century: its role in gestational diabetes mellitus, prevention of preeclampsia and cancer, and the promotion of longevity. Am J Obstet Gynecol. (2017) 217:282–302. doi: 10.1016/j.ajog.2017.06.003

PubMed Abstract | Crossref Full Text | Google Scholar

9. Tosti G, Barberio A, Tartaglione L, Rizzi A, Di Leo M, Viti L, et al. Lights and shadows on the use of metformin in pregnancy: from the preconception phase to breastfeeding and beyond. Front Endocrinol. (2023) 14:1176623. doi: 10.3389/fendo.2023.1176623

PubMed Abstract | Crossref Full Text | Google Scholar

10. Bolte E, Dean T, Garcia B, Seferovic MD, Sauter K, Hummel G, et al. Initiation of metformin in early pregnancy results in fetal bioaccumulation, growth restriction, and renal dysmorphology in a primate model. Am J Obstet Gynecol. (2024). 231:352.e1–16. doi: 10.1016/j.ajog.2024.06.002

PubMed Abstract | Crossref Full Text | Google Scholar

11. Owen MD, Baker BC, Scott EM, Forbes K. Interaction between Metformin, Folate and Vitamin B(12) and the potential impact on fetal growth and long-term metabolic health in diabetic pregnancies. Int J Mol Sci. (2021) 22:5759. doi: 10.3390/ijms22115759

PubMed Abstract | Crossref Full Text | Google Scholar

12. Tertti K, Ekblad U, Vahlberg T, Rönnemaa T. Comparison of metformin and insulin in the treatment of gestational diabetes: a retrospective, case-control study. Rev Diabet Stud. (2008) 5:95–101. doi: 10.1900/RDS.2008.5.95

PubMed Abstract | Crossref Full Text | Google Scholar

13. Balani J, Hyer S, Johnson A, Shehata H. Pregnancy outcomes after metformin treatment for gestational diabetes: a case-control study. Obstet Med. (2012) 5:78–82. doi: 10.1258/om.2012.110092

PubMed Abstract | Crossref Full Text | Google Scholar

14. Ruholamin S, Eshaghian S, Allame Z. Neonatal outcomes in women with gestational diabetes mellitus treated with metformin in compare with insulin: a randomized clinical trial. J Res Med Sci. (2014) 19:970–5.

PubMed Abstract | Google Scholar

15. Boggess KA, Valint A, Refuerzo JS, Zork N, Battarbee AN, Eichelberger K, et al. Metformin plus insulin for preexisting diabetes or gestational diabetes in early pregnancy: the MOMPOD randomized clinical trial. JAMA. (2023) 330:2182–90. doi: 10.1001/jama.2023.22949

PubMed Abstract | Crossref Full Text | Google Scholar

16. Chiswick C, Reynolds RM, Denison F, Drake AJ, Forbes S, Newby DE, et al. Effect of metformin on maternal and fetal outcomes in obese pregnant women (EMPOWaR): a randomised, double-blind, placebo-controlled trial. Lancet Diabetes Endocrinol. (2015) 3:778–86. doi: 10.1016/S2213-8587(15)00219-3

PubMed Abstract | Crossref Full Text | Google Scholar

17. Bowker SL, Savu A, Yeung RO, Johnson JA, Ryan EA, Kaul P. Patterns of glucose-lowering therapies and neonatal outcomes in the treatment of gestational diabetes in Canada, 2009–2014. Diabet Med. (2017) 34:1296–302. doi: 10.1111/dme.13394

PubMed Abstract | Crossref Full Text | Google Scholar

18. Eid SR, Moustafa RSI, Salah MM, Hanafy SK, Aly RH, Mostafa WFG, et al. Is metformin a viable alternative to insulin in the treatment of gestational diabetes mellitus (GDM)? Comparison of maternal and neonatal outcomes. Egypt Pediatr Assoc Gaz. (2018) 66:15–21. doi: 10.1016/j.epag.2018.01.002

Crossref Full Text | Google Scholar

19. McGrath RT, Glastras SJ, Scott ES, Hocking SL, Fulcher GR. Outcomes for women with gestational diabetes treated with metformin: a retrospective, case-control study. J Clin Med. (2018) 7:50. doi: 10.3390/jcm7030050

PubMed Abstract | Crossref Full Text | Google Scholar

20. Simeonova-Krstevska S, Bogoev M, Bogoeva K, Zisovska E, Samardziski I, Velkoska-Nakova V, et al. Maternal and neonatal outcomes in pregnant women with gestational diabetes mellitus treated with diet, metformin or insulin. Open Access Maced J Med Sci. (2018) 6:803–7. doi: 10.3889/oamjms.2018.200

PubMed Abstract | Crossref Full Text | Google Scholar

21. Feig DS, Donovan LE, Zinman B, Sanchez JJ, Asztalos E, Ryan EA, et al. Metformin in women with type 2 diabetes in pregnancy (MiTy): a multicentre, international, randomised, placebo-controlled trial. Lancet Diabetes Endocrinol. (2020) 8:834–44. doi: 10.1016/S2213-8587(20)30310-7

PubMed Abstract | Crossref Full Text | Google Scholar

22. Lin SF, Chang SH, Kuo CF, Lin WT, Chiou MJ, Huang YT. Association of pregnancy outcomes in women with type 2 diabetes treated with metformin versus insulin when becoming pregnant. BMC Pregnancy Childbirth. (2020) 20:512. doi: 10.1186/s12884-020-03207-0

PubMed Abstract | Crossref Full Text | Google Scholar

23. Huhtala MS, Rönnemaa T, Pellonperä O, Tertti K. Cord serum metabolome and birth weight in patients with gestational diabetes treated with metformin, insulin, or diet alone. BMJ Open Diabetes Res Care. (2021) 9:e002022. doi: 10.1136/bmjdrc-2020-002022

PubMed Abstract | Crossref Full Text | Google Scholar

24. Picón-César MJ, Molina-Vega M, Suárez-Arana M, González-Mesa E, Sola-Moyano AP, Roldan-López R, et al. Metformin for gestational diabetes study: metformin vs insulin in gestational diabetes: glycemic control and obstetrical and perinatal outcomes: randomized prospective trial. Am J Obstet Gynecol. (2021) 225:517.e1–17. doi: 10.1016/j.ajog.2021.04.229

PubMed Abstract | Crossref Full Text | Google Scholar

25. Brand KM, Thoren R, Sõnajalg J, Boutmy E, Foch C, Schlachter J, et al. Metformin in pregnancy and risk of abnormal growth outcomes at birth: a register-based cohort study. BMJ Open Diabetes Res Care. (2022) 10:e003056. doi: 10.1136/bmjdrc-2022-003056

PubMed Abstract | Crossref Full Text | Google Scholar

26. Brand KMG, Saarelainen L, Sonajalg J, Boutmy E, Foch C, Vääräsmäki M, et al. Metformin in pregnancy and risk of adverse long-term outcomes: a register-based cohort study. BMJ Open Diabetes Res Care. (2022) 10:e002363. doi: 10.1136/bmjdrc-2021-002363

PubMed Abstract | Crossref Full Text | Google Scholar

27. Fornes R, Simin J, Nguyen MH, Cruz G, Crisosto N, van der Schaaf M, et al. Pregnancy, perinatal and childhood outcomes in women with and without polycystic ovary syndrome and metformin during pregnancy: a nationwide population-based study. Reprod Biol Endocrinol. (2022) 20:30. doi: 10.1186/s12958-022-00905-6

PubMed Abstract | Crossref Full Text | Google Scholar

28. Brzozowska MM, Puvanendran A, Bliuc D, Zuschmann A, Piotrowicz AK, O'Sullivan A, et al. Predictors for pharmacological therapy and perinatal outcomes with metformin treatment in women with gestational diabetes. Front Endocrinol. (2023) 14:1119134. doi: 10.3389/fendo.2023.1119134

PubMed Abstract | Crossref Full Text | Google Scholar

29. Dunne F, Newman C, Alvarez-Iglesias A, Ferguson J, Smyth A, Browne M, et al. Early metformin in gestational diabetes: a randomized clinical trial. JAMA. (2023). 330:1547–56. doi: 10.1001/jama.2023.19869

PubMed Abstract | Crossref Full Text | Google Scholar

30. Yu YH, Platt RW, Reynier P, Yu OHY, Filion KB, et al. Use of metformin and insulin among pregnant women with gestation diabetes in the United Kingdom: a population-based cohort study. Diabet Med. (2023) 40:e15108. doi: 10.1111/dme.15108

PubMed Abstract | Crossref Full Text | Google Scholar

31. Nilsen G, Simpson MR, Hanem LGE, Løvvik TS, Ødegård R, Stokkeland LMT, et al. Anthropometrics of neonates born to mothers with PCOS with metformin or placebo exposure in utero. Acta Obstet Gynecol Scand. (2024) 103:176–87. doi: 10.1111/aogs.14637

PubMed Abstract | Crossref Full Text | Google Scholar

32. Tarry-Adkins JL, Aiken CE, Ozanne SE. Neonatal, infant, and childhood growth following metformin versus insulin treatment for gestational diabetes: a systematic review and meta-analysis. PLoS Med. (2019). 16:e1002848. doi: 10.1371/journal.pmed.1002848

PubMed Abstract | Crossref Full Text | Google Scholar

33. Benham JL, Donovan LE, Yamamoto JM. Metformin in pregnancy for women with type 2 diabetes: a review. Curr Diab Rep. (2021) 21:36. doi: 10.1007/s11892-021-01409-0

PubMed Abstract | Crossref Full Text | Google Scholar

34. Cluver CA, Hiscock R, Decloedt EH, Hall DR, Schell S, Mol BW, et al. Use of metformin to prolong gestation in preterm pre-eclampsia: randomised, double blind, placebo controlled trial. BMJ. (2021) 374:n2103. doi: 10.1136/bmj.n2103

PubMed Abstract | Crossref Full Text | Google Scholar

35. Soobryan N, Murugesan S, Pandiyan A, Moodley J, Mackraj I. Angiogenic dysregulation in pregnancy-related hypertension-a role for metformin. Reprod Sci. (2018) 25:1531–9. doi: 10.1177/1933719118773484

PubMed Abstract | Crossref Full Text | Google Scholar

36. Feig DS, Zinman B, Asztalos E, Donovan LE, Shah PS, Sanchez JJ, et al. Determinants of small for gestational age in women with type 2 diabetes in pregnancy: who should receive metformin? Diabetes Care. (2022) 45:1532–9. doi: 10.2337/dc22-0013

PubMed Abstract | Crossref Full Text | Google Scholar

37. Lv S, Wang J, Xu Y. Safety of insulin analogs during pregnancy: a meta-analysis. Arch Gynecol Obstet. (2015) 292:749–56. doi: 10.1007/s00404-015-3692-3

PubMed Abstract | Crossref Full Text | Google Scholar