Treatment outcomes and safety of metformin versus insulin in gestational diabetes mellitus: A systematic review and meta-analysis
7 affiliations
- 1Department of Internal Medicine, College of Medicine, Imam Mohammed Ibn Saud Islamic University (IMSIU), Riyadh, Saudi Arabia
- 2College of Medicine, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh, Saudi Arabia
- 3Ataturk University, Erzurum, Turkey
- 4College of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
- 5College of Medicine, Jouf University, Sakaka, Saudi Arabia
- 6College of Medicine, King Faisal University, Al hofuf, Al Ahsa, Saudi Arabia
- 7College of Medicine, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
Abstract
Gestational diabetes mellitus (GDM) is a common pregnancy complication associated with adverse maternal and neonatal outcomes. While insulin remains the traditional treatment, metformin has emerged as a potential alternative due to its ease of use and favorable metabolic effects. This systematic review and meta-analysis aimed to compare the efficacy and safety of metformin versus insulin in the management of GDM. This review was registered with International Prospective Register of Systematic Reviews (PROSPERO) (CRD42025644196) and conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A comprehensive literature search was performed using PubMed and Google Scholar for studies published between 2020 and 2025. Eligible studies were randomized controlled trials (RCTs) comparing metformin and insulin in pregnant women diagnosed with GDM and reporting relevant maternal or neonatal outcomes. Data screening and extraction were performed using Rayyan software. Statistical analysis was conducted using Stata version 17. Pooled effect sizes were calculated using a random-effects model. Standardized mean differences (SMDs) and odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess continuous and dichotomous outcomes, respectively. Heterogeneity was evaluated using the I² statistic and Cochran’s Q test. Publication bias was assessed using funnel plots and Egger’s test. Twenty-two RCTs met the inclusion criteria. Metformin achieved glycemic control comparable to insulin, with a pooled SMD for fasting blood glucose (FBG) of –0.29 (95% CI: –0.55 to –0.03; P = 0.03). No significant difference was observed in glycated hemoglobin (HbA1c) levels (SMD = –0.26; 95% CI: –0.75 to 0.23; P = 0.30). Metformin was associated with significantly less maternal weight gain and a reduced risk of neonatal hypoglycemia (OR = 2.72; 95% CI: 1.02–7.26; P = 0.05). The incidence of pre-eclampsia and hypertensive disorders was similar between groups. Patient satisfaction was consistently higher in the metformin group, with most participants preferring it over insulin. Funnel plots and Egger’s test indicated no significant publication bias. Metformin is a safe and effective alternative to insulin for the management of GDM in most pregnant women, offering comparable glycemic control, reduced maternal weight gain, lower risk of neonatal hypoglycemia, and higher patient acceptability. While some patients may still require insulin supplementation, metformin represents a valuable first-line option, especially in settings where injection therapy is less feasible or poorly tolerated.
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BibTeX
@article{alnemer2026treatment,
title = {{Treatment outcomes and safety of metformin versus insulin in gestational diabetes mellitus: A systematic review and meta-analysis}},
author = {Khalid Al-Nemer and Hala Alruwaili and Ayesha Alnashwan and Marwa Akram and Maan Almuzaini and Arwa Aloraini and Rahaf Alsaedi and Basil Alshammari and Layin Almasoud and Musab Alsulami and Leen Almohayya and Waad Aljadani and Meshal Alzakari},
journal = {Journal of family medicine and primary care},
year = {2026},
month = jul,
doi = {10.4103/jfmpc.jfmpc_2277_25},
url = {https://europepmc.org/article/PMC/PMC13722223},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Treatment outcomes and safety of metformin versus insulin in gestational diabetes mellitus: A systematic review and meta-analysis
AU - Khalid Al-Nemer
AU - Hala Alruwaili
AU - Ayesha Alnashwan
AU - Marwa Akram
AU - Maan Almuzaini
AU - Arwa Aloraini
AU - Rahaf Alsaedi
AU - Basil Alshammari
AU - Layin Almasoud
AU - Musab Alsulami
AU - Leen Almohayya
AU - Waad Aljadani
AU - Meshal Alzakari
PY - 2026
DA - 2026/07/01
JO - Journal of family medicine and primary care
DO - 10.4103/jfmpc.jfmpc_2277_25
UR - https://europepmc.org/article/PMC/PMC13722223
AB - Gestational diabetes mellitus (GDM) is a common pregnancy complication associated with adverse maternal and neonatal outcomes. While insulin remains the traditional treatment, metformin has emerged as a potential alternative due to its ease of use and favorable metabolic effects. This systematic review and meta-analysis aimed to compare the efficacy and safety of metformin versus insulin in the management of GDM. This review was registered with International Prospective Register of Systematic Reviews (PROSPERO) (CRD42025644196) and conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A comprehensive literature search was performed using PubMed and Google Scholar for studies published between 2020 and 2025. Eligible studies were randomized controlled trials (RCTs) comparing metformin and insulin in pregnant women diagnosed with GDM and reporting relevant maternal or neonatal outcomes. Data screening and extraction were performed using Rayyan software. Statistical analysis was conducted using Stata version 17. Pooled effect sizes were calculated using a random-effects model. Standardized mean differences (SMDs) and odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess continuous and dichotomous outcomes, respectively. Heterogeneity was evaluated using the I² statistic and Cochran’s Q test. Publication bias was assessed using funnel plots and Egger’s test. Twenty-two RCTs met the inclusion criteria. Metformin achieved glycemic control comparable to insulin, with a pooled SMD for fasting blood glucose (FBG) of –0.29 (95% CI: –0.55 to –0.03; P = 0.03). No significant difference was observed in glycated hemoglobin (HbA1c) levels (SMD = –0.26; 95% CI: –0.75 to 0.23; P = 0.30). Metformin was associated with significantly less maternal weight gain and a reduced risk of neonatal hypoglycemia (OR = 2.72; 95% CI: 1.02–7.26; P = 0.05). The incidence of pre-eclampsia and hypertensive disorders was similar between groups. Patient satisfaction was consistently higher in the metformin group, with most participants preferring it over insulin. Funnel plots and Egger’s test indicated no significant publication bias. Metformin is a safe and effective alternative to insulin for the management of GDM in most pregnant women, offering comparable glycemic control, reduced maternal weight gain, lower risk of neonatal hypoglycemia, and higher patient acceptability. While some patients may still require insulin supplementation, metformin represents a valuable first-line option, especially in settings where injection therapy is less feasible or poorly tolerated.
SN - 2249-4863
SN - 2278-7135
ER -