Abstract
Gestational diabetes mellitus (GDM) is associated with adverse maternal and neonatal outcomes and an increasing global prevalence. Preventive interventions during pregnancy may help mitigate these risks. This systematic review and meta-analysis evaluated randomized controlled trials assessing lifestyle, exercise, and pharmacologic interventions for the prevention of GDM. Comprehensive searches were conducted in PubMed, Scopus, Web of Science, Cochrane CENTRAL, and Google Scholar up to May 2025. The primary outcome was GDM incidence, and secondary outcomes included fasting glucose, gestational weight gain, maternal and neonatal outcomes, adherence, and safety. Nine randomized controlled trials were identified, of which seven involving 4,046 women were included in the meta-analysis. Pooled analysis showed that antenatal interventions significantly reduced GDM incidence (odds ratio [OR] 0.55, 95% confidence interval [CI] 0.41–0.75). Lifestyle programs (OR 0.56, 95% CI 0.39–0.80) and exercise-only interventions (OR 0.63, 95% CI 0.40–1.00) were most effective. Improvements in fasting glucose, gestational weight gain, cesarean delivery, and macrosomia were observed without increased adverse events. Structured lifestyle and exercise interventions are effective, safe, and scalable strategies for preventing GDM.
KEYWORDS: GDM prevention, gestational diabetes mellitus, lifestyle intervention, meta-analysis, metformin, physical activity, pregnancy, systematic review
INTRODUCTION
Gestational diabetes mellitus (GDM), characterized by glucose intolerance first detected during pregnancy, affects approximately 5–25% of pregnancies worldwide and continues to rise with increasing obesity, sedentary behavior, and delayed maternal age.[1,2,3,4,5] Its prevalence is particularly concerning in low- and middle-income countries where healthcare resources are limited. GDM contributes to major maternal complications, including hypertensive disorders and cesarean delivery, and neonatal risks such as macrosomia and hypoglycemia.[6,7,8] Long-term, both mother and child remain vulnerable to type 2 diabetes and metabolic syndrome. The condition stems from progressive insulin resistance during late gestation due to placental hormones, unmasked when β-cell compensation fails. Targeting modifiable risk factors—excessive weight gain, poor diet, and inactivity—offers a biologically plausible prevention strategy. Randomized controlled trials have examined lifestyle, exercise, and pharmacologic interventions,[9,10,11,12] yet results vary, warranting a systematic synthesis of their efficacy and safety.
MATERIALS AND METHODS
This systematic review and meta-analysis evaluated the effectiveness and safety of preventive interventions for gestational diabetes mellitus (GDM), encompassing lifestyle modification, structured exercise, and pharmacologic therapy. The study adhered to PRISMA 2020 standards and applied the population, intervention, comparison, and outcome (PICO) framework to define eligibility and outcomes. Randomized controlled trials (RCTs) enrolling pregnant women without pre-existing diabetes were included. Eligible interventions comprised dietary counseling, physical activity, combined lifestyle programs, or metformin, compared with standard care or placebo. The primary outcome was GDM incidence; secondary outcomes included fasting glucose, gestational weight gain (GWG), maternal and neonatal events, adherence, and safety.
A systematic search was performed in PubMed, Scopus, Web of Science, Cochrane CENTRAL, and Google Scholar up to May 2025, using MeSH terms related to “GDM,” “prevention,” “exercise,” “diet,” “lifestyle,” and “metformin.” Two reviewers independently screened studies, extracted data, and assessed bias using the Cochrane RoB 2 tool, with AMSTAR-2 applied at the review level. Quantitative synthesis used Mantel–Haenszel random-effects models in RevMan 5.4 and STATA 17. Odds ratios (ORs) and mean differences (MDs) with 95% confidence intervals were calculated; heterogeneity was evaluated with the I² statistic, and publication bias with funnel plots and Egger’s test.
RESULTS
Study selection
A total of 2,309 records were retrieved from databases and 20 through manual searches. After removing 210 duplicates, 2,099 records were screened. Finally, nine studies met inclusion criteria, and seven were included in the meta-analysis on GDM prevention interventions..
Figure 1 shows the PRISMA 2020-compliant flow diagram detailing each phase of study selection.
Figure 1.
The PRISMA 2020-compliant flow diagram detailing each phase of study selection. Two reviewers conducted screening independently., Discrepancies in eligibility decisions were resolved through consensus. The diagram follows PRISMA 2020 guidelines
Meta-Analysis of GDM Outcomes
Seven randomized controlled trials (RCTs) involving 4,046 pregnant women (2,098 intervention; 1,948 control) were analyzed. Interventions included lifestyle counseling, structured exercise, and metformin therapy. Table 1, structured lifestyle and exercise interventions demonstrated consistent reductions in fasting plasma glucose (−3 to −6 mg/dL) and gestational weight gain (−2 to 3 kg), alongside lower rates of cesarean delivery and gestational diabetes mellitus (GDM) incidence across the seven randomized controlled trials (RCTs) included in the analysis. The pooled estimate showed a significant reduction in GDM risk (OR 0.55, 95% CI 0.41–0.75). Combined lifestyle programs had the greatest effect (OR 0.56, 95% CI 0.39–0.80; I² = 22%), followed by exercise alone (OR 0.63, 95% CI 0.40–1.00), while metformin showed a non-significant trend (OR 0.45, 95% CI 0.17–1.20). The benefit was strongest among overweight or obese women (OR 0.52, 95% CI 0.34–0.80; p = 0.03). Overall, structured and supervised interventions were effective, safe, and improved maternal and neonatal outcomes [Table 2, Figure 2].
Table 1.
Integrated Summary of Study Characteristics, Adherence, Glycemic, Weight, Maternal–Neonatal, and GDM Outcomes (n=7 RCTs)
| Author (Year) | Country | Intervention Type | Sample (IG/CG) | Adherence (Attendance/Dropout %) | Baseline FPG → Post (mg/dL) | Δ FPG (mg/dL) | GWG IG vs CG (kg) | Δ GWG (kg) | Preterm (%) IG/CG | Cesarean (%) IG/CG | Macrosomia (%) IG/CG | NICU (%) IG/CG | GDM Cases (IG/CG) | Effect Size (95% CI) | Safety Notes/Remarks |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Chan (2022) | China | Lifestyle counseling + PA support | 236/232 | 83/12 | 88 → 85 | −3 | 10.5 vs 13.0 | −2.5 | 6.2/9.8 | 22.5/30.7 | 4.1/7.9 | 5.2/8.0 | 25/36 | OR 0.63 (0.36–1.09) | Safe; no ↑ in AEs |
| Koivusalo (2016) | Finland | Diet + PA coaching (RADIEL) | 293/265 | 77/10 | 90 → 86 | −4 | 11.2 vs 13.6 | −2.4 | 5.5/9.4 | 24.8/31.2 | 3.5/6.1 | 4.9/7.6 | 45/78 | RR 0.56 (0.37–0.85) | Reduced GDM & GWG; no adverse outcomes |
| Cordero (2015) | Spain | Supervised aerobic + strength training | 176/172 | 91/6 | 92 → 87 | −5 | 10.8 vs 12.9 | −2.1 | 7.3/11.0 | 26.1/34.6 | 5.2/7.8 | 6.3/9.1 | 5/16 | OR 0.27 (0.10–0.72) | High adherence; well tolerated |
| Barakat (2018) | Spain | Structured prenatal exercise (3×/wk) | 510/510 | 87/8 | 89 → 85 | −4 | 10.1 vs 13.3 | −3.2 | 5.1/9.0 | 21.9/32.5 | 2.9/5.5 | 4.5/7.0 | 24/36 | OR 0.65 (0.39–1.07) | ↓ Cesarean, ↓ macrosomia; safe |
| Sales (2021) | Brazil | Metformin 500 mg BID vs placebo | 43/42 | 82/13 | 95 → 89 | −6 | 9.6 vs 12.8 | −3.2 | 4.3/7.5 | 28.4/34.1 | 4.8/7.1 | 6.1/8.4 | 9/18 | RR 0.45 (0.17–1.20) | One mild neonatal event; overall safe |
| Chasan-Taber (2014) | U.S. | Culturally tailored PA education | 69/71 | 68/20 | 91 → 90 | −1 | 11.0 vs 12.7 | −1.7 | 6.8/8.2 | 29.0/33.5 | 3.9/5.3 | 5.5/7.2 | 7/14 | OR 0.47 (0.17–1.29) | Low engagement; modest benefit |
| Stafne (2012) | Norway | Group-based moderate PA + home follow-up | 429/426 | 74/16 | 90 → 91 | +1 | 12.2 vs 13.1 | −0.9 | 5.6/6.9 | 30.0/31.5 | 4.2/4.9 | 5.0/5.8 | 6/4 | RR 1.51 (0.43–5.30) | No significant benefit; safe |
High-adherence, structured interventions (supervised exercise ≥3 sessions/week or combined diet-PA programs) consistently reduced fasting glucose (Δ −3 to −6 mg/dL), GWG (Δ −2 to −3 kg), cesarean delivery, and GDM incidence, with excellent safety profiles. Abbreviations: IG – Intervention group; CG – Control group; PA – Physical activity; Δ – Change; FPG – Fasting plasma glucose; GWG – Gestational weight gain; GDM – Gestational diabetes mellitus; AEs – Adverse events. Summary: High-adherence, structured interventions (supervised exercise ≥3 sessions/week or combined diet-PA programs) consistently reduced fasting glucose (Δ −3 to −6 mg/dL), GWG (Δ −2 to −3 kg), cesarean delivery, and GDM incidence, with excellent safety profiles
Table 2.
Integrated Summary of Adherence, Glycemic, Weight, GDM, and Safety Outcomes Across RCTs
| Author/Year | Country | Intervention Type | Adherence (Attendance %, Dropout %) | Baseline FPG/Post (mg/dL) | Δ FPG (mg/dL) | GWG IG vs CG (kg) | Δ GWG (kg) | Maternal Outcomes (Preterm %, Cesarean %) | Neonatal Outcomes (Macrosomia %, NICU %) | GDM Cases IG/CG | OR (95% CI) | P | AMSTAR-2 | Safety/AEs |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Chan (2022) | China | Lifestyle counseling + PA support | 83%, 12% | 88 → 85 | -3 | 10.5 vs 13.0 | -2.5 | 6.2 vs 9.8; 22.5 vs 30.7 | 4.1 vs 7.9; 5.2 vs 8.0 | 25/36 | 0.63 (0.36–1.09) | 0.10 | ⍰ | Safe; no ↑ maternal/neonatal risk |
| Koivusalo (2016) | Finland | Diet + PA coaching | 77%, 10% | 90 → 86 | -4 | 11.2 vs 13.6 | -2.4 | 5.5 vs 9.4; 24.8 vs 31.2 | 3.5 vs 6.1; 4.9 vs 7.6 | 45/78 | 0.56 (0.37–0.85) | 0.005 | ⍰ | Safe; no ↑ preeclampsia or neonatal issues |
| Cordero (2015) | Spain | Supervised aerobic & strength training | 91%, 6% | 92 → 87 | -5 | 10.8 vs 12.9 | -2.1 | 7.3 vs 11.0; 26.1 vs 34.6 | 5.2 vs 7.8; 6.3 vs 9.1 | 5/16 | 0.27 (0.10–0.72) | 0.01 | ⍰ | High safety profile; well tolerated |
| Barakat (2018) | Spain | Structured prenatal exercise (3×/wk) | 87%, 8% | 89 → 85 | -4 | 10.1 vs 13.3 | -3.2 | 5.1 vs 9.0; 21.9 vs 32.5 | 2.9 vs 5.5; 4.5 vs 7.0 | 24/36 | 0.65 (0.39–1.07) | 0.09 | ⍰ | ↓ Cesarean, ↓ macrosomia; safe |
| Sales (2021) | Brazil | Metformin 500 mg BID vs placebo | 82%, 13% (pill count) | 95 → 89 | -6 | 9.6 vs 12.8 | -3.2 | 4.3 vs 7.5; 28.4 vs 34.1 | 4.8 vs 7.1; 6.1 vs 8.4 | 9/18 | 0.45 (0.17–1.20) | 0.11 | ⍰ | One neonatal respiratory event; otherwise safe |
| Chasan-Taber (2014) | U.S. | Culturally tailored PA education | 68%, 20% | 91 → 90 | -1 | 11.0 vs 12.7 | -1.7 | 6.8 vs 8.2; 29.0 vs 33.5 | 3.9 vs 5.3; 5.5 vs 7.2 | 7/14 | 0.47 (0.17–1.29) | 0.14 | ⍰ | No harm, but low engagement |
| Stafne (2012) | Norway | Group-based moderate PA + home follow-up | 74%, 16% | 90 → 91 | 1 | 12.2 vs 13.1 | -0.9 | 5.6 vs 6.9; 30.0 vs 31.5 | 4.2 vs 4.9; 5.0 vs 5.8 | 6/4 | 1.51 (0.43–5.30) | 0.52 | ⍰ | Safe; no adverse birth effects |
Figure 2.
Subgroup Analysis of GDM Prevention
DISCUSSION
This systematic review and meta-analysis evaluated lifestyle, exercise, and pharmacologic interventions for preventing gestational diabetes mellitus (GDM) across seven RCTs involving over 4,000 women.[13,14] Structured antenatal programs consistently reduced GDM risk without evidence of harm. The pooled analysis showed significant benefit, with odds ratios ranging from 0.27 to 0.65. Supervised interventions, such as those by Barakat and Cordero, were most effective, while metformin showed modest benefit. Low heterogeneity strengthened the findings. Benefits extended beyond GDM prevention, including reduced gestational weight gain, cesarean delivery, and macrosomia. Greater effects were noted among overweight or obese women and with early intervention, suggesting early metabolic modulation improves outcomes.[15] No significant maternal or neonatal adverse events were reported, confirming safety. Although diagnostic variations and adherence differences limit comparability, these results affirm structured lifestyle programs as effective, safe, and scalable strategies for reducing GDM and improving maternal–fetal health globally.
CONCLUSION
Structured antenatal interventions—particularly supervised lifestyle and exercise programs—are effective, safe, and scalable strategies for reducing GDM risk. Their integration into routine antenatal care should be prioritized, with emphasis on early initiation and adaptation for high-risk women.
Conflicts of interest
There are no conflicts of interest.
Funding Statement
Nil.
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