Metformin vs insulin in the management of gestational diabetes: a meta-analysis

Juan Gui, Qing Liu, Ling Feng, Juan Gui, Qing Liu, Ling Feng

Abstract

Background: Nowadays, there have been increasing studies comparing metformin with insulin. But the use of metformin in pregnant women is still controversial, therefore, we aim to examine the efficiency and safety of metformin by conducting a meta-analysis of randomized controlled trials (RCTs) comparing the effects of metformin with insulin on glycemic control, maternal and neonatal outcomes in gestational diabetes mellitus (GDM).

Methods: We used the key words "gestational diabetes" in combination with "metformin" and searched the databases including Pubmed, the Cochrane Library, Web of knowledge, and Clinical Trial Registries. A random-effects model was used to compute the summary risk estimates.

Results: Meta-analysis of 5 RCTs involving 1270 participants detected that average weight gains after enrollment were much lower in the metformin group (n = 1006, P = 0.003, SMD = -0.47, 95%CI [-0.77 to -0.16]); average gestational ages at delivery were significantly lower in the metformin group (n = 1270, P = 0.02, SMD = -0.14, 95%CI [-0.25 to -0.03]); incidence of preterm birth was significantly more in metformin group (n = 1110, P = 0.01, OR = 1.74, 95%CI [1.13 to 2.68]); the incidence of pregnancy induced hypertension was significantly less in the metformin group (n = 1110, P = 0.02, OR = 0.52, 95%CI [0.30 to 0.90]). The fasting blood sugar levels of OGTT were significantly lower in the metformin only group than in the supplemental insulin group (n = 478, P = 0.0006, SMD = -0.83, 95%CI [-1.31 to -0.36]).

Conclusions: Metformin is comparable with insulin in glycemic control and neonatal outcomes. It might be more suitable for women with mild GDM. This meta-analysis also provides some significant benefits and risks of the use of metformin in GDM and help to inform further development of management guidelines.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1. Flow of study identification, inclusion,…
Figure 1. Flow of study identification, inclusion, and exclusion.
Figure 2. Forest plot of main maternal…
Figure 2. Forest plot of main maternal risks comparing metformin with insulin.
a: weight gain after enrollment; b: gestational age at delivery; c: incidence of preterm birth; d: incidence of PIH; e: incidence of preeclampsia. SMD: standard mean differences; CI: confidence intervals; OR: odds ratio; PIH: pregnancy induced hypertension.
Figure 3. Forest plot of main neonatal…
Figure 3. Forest plot of main neonatal risks comparing metformin with insulin.
a: birth weight; b: incidence of LGA infants; c: incidence of SGA infants; d: incidence of hypoglycemia. SMD: standard mean differences; CI: confidence intervals; OR: odds ratio; LGA: large for gestational age; SGA: small for gestational age.

References

    1. Association AD (2010) Diagnosis and Classification of Diabetes Mellitus. Diabetes Care 34: S62–S69.
    1. Maymone AC, Baillargeon JP, Menard J, Ardilouze JL (2011) Oral hypoglycemic agents for gestational diabetes mellitus? Expert Opin Drug Saf 10: 227–238.
    1. Dempsey JC, Butler CL, Sorensen TK, Lee IM, Thompson ML, et al. (2004) A case-control study of maternal recreational physical activity and risk of gestational diabetes mellitus. Diabetes Res Clin Pract 66: 203–215.
    1. Ben-Haroush A, Yogev Y, Hod M (2004) Epidemiology of gestational diabetes mellitus and its association with Type 2 diabetes. Diabet Med 21: 103–113.
    1. Boulot P, Chabbert-Buffet N, d'Ercole C, Floriot M, Fontaine P, et al. (2003) French multicentric survey of outcome of pregnancy in women with pregestational diabetes. Diabetes Care 26: 2990–2993.
    1. Rowan JA, Gao W, Hague WM, McIntyre HD (2010) Glycemia and its relationship to outcomes in the metformin in gestational diabetes trial. Diabetes Care 33: 9–16.
    1. de Veciana M, Major CA, Morgan MA, Asrat T, Toohey JS, et al. (1995) Postprandial versus preprandial blood glucose monitoring in women with gestational diabetes mellitus requiring insulin therapy. N Engl J Med 333: 1237–1241.
    1. Esakoff TF, Cheng YW, Sparks TN, Caughey AB (2009) The association between birthweight 4000 g or greater and perinatal outcomes in patients with and without gestational diabetes mellitus. Am J Obstet Gynecol 200: 672 e671–674.
    1. Metzger BE, Gabbe SG, Persson B, Buchanan TA, Catalano PA, et al. (2010) International association of diabetes and pregnancy study groups recommendations on the diagnosis and classification of hyperglycemia in pregnancy. Diabetes Care 33: 676–682.
    1. Crowther CA, Hiller JE, Moss JR, McPhee AJ, Jeffries WS, et al. (2005) Effect of treatment of gestational diabetes mellitus on pregnancy outcomes. N Engl J Med 352: 2477–2486.
    1. Evensen AE (2012) Update on gestational diabetes mellitus. Prim Care 39: 83–94.
    1. Glueck CJ, Goldenberg N, Streicher P, Wang P (2002) The contentious nature of gestational diabetes: diet, insulin, glyburide and metformin. Expert Opin Pharmacother 3: 1557–1568.
    1. Association AD (2009) Standards of medical care in diabetes–2009. Diabetes Care 32 Suppl 1S13–61.
    1. Nicholson W, Baptiste-Roberts K (2011) Oral hypoglycaemic agents during pregnancy: The evidence for effectiveness and safety. Best Pract Res Clin Obstet Gynaecol 25: 51–63.
    1. Norman RJ, Wang JX, Hague W (2004) Should we continue or stop insulin sensitizing drugs during pregnancy? Curr Opin Obstet Gynecol 16: 245–250.
    1. Simmons D (2010) Metformin treatment for Type 2 diabetes in pregnancy? Best Pract Res Clin Endocrinol Metab 24: 625–634.
    1. Ijas H, Vaarasmaki M, Morin-Papunen L, Keravuo R, Ebeling T, et al. (2011) Metformin should be considered in the treatment of gestational diabetes: a prospective randomised study. BJOG 118: 880–885.
    1. Nanovskaya TN, Nekhayeva IA, Patrikeeva SL, Hankins GD, Ahmed MS (2006) Transfer of metformin across the dually perfused human placental lobule. Am J Obstet Gynecol 195: 1081–1085.
    1. Kovo M, Haroutiunian S, Feldman N, Hoffman A, Glezerman M (2008) Determination of metformin transfer across the human placenta using a dually perfused ex vivo placental cotyledon model. Eur J Obstet Gynecol Reprod Biol 136: 29–33.
    1. Tertti K, Ekblad U, Vahlberg T, Ronnemaa T (2008) Comparison of metformin and insulin in the treatment of gestational diabetes: a retrospective, case-control study. Rev Diabet Stud 5: 95–101.
    1. Balani J, Hyer SL, Rodin DA, Shehata H (2009) Pregnancy outcomes in women with gestational diabetes treated with metformin or insulin: a case-control study. Diabet Med 26: 798–802.
    1. Goh JE, Sadler L, Rowan J (2011) Metformin for gestational diabetes in routine clinical practice. Diabet Med 28: 1082–1087.
    1. Rai L, Meenakshi D, Kamath A (2009) Metformin–a convenient alternative to insulin for Indian women with diabetes in pregnancy. Indian J Med Sci 63: 491–497.
    1. Rowan JA (2007) A trial in progress: gestational diabetes. Treatment with metformin compared with insulin (the Metformin in Gestational Diabetes [MiG] trial). Diabetes Care 30 Suppl 2S214–219.
    1. Tertti K, Ekblad U, Koskinen P, Vahlberg T, Ronnemaa T (2012) Metformin vs. insulin in gestational diabetes. A randomized study characterizing metformin patients needing additional insulin. Diabetes Obes Metab. doi: 10.1111/dom.12017.
    1. Niromanesh S, Alavi A, Sharbaf FR, Amjadi N, Moosavi S, et al. (2012) Metformin compared with insulin in the management of gestational diabetes mellitus: A randomized clinical trial. Diabetes Res Clin Pract 98: 422–429.
    1. Rowan JA, Hague WM, Gao W, Battin MR, Moore MP (2008) Metformin versus insulin for the treatment of gestational diabetes. N Engl J Med 358: 2003–2015.
    1. Moore LE, Briery CM, Clokey D, Martin RW, Williford NJ, et al. (2007) Metformin and insulin in the management of gestational diabetes mellitus: preliminary results of a comparison. J Reprod Med 52: 1011–1015.
    1. Dhulkotia JS, Ola B, Fraser R, Farrell T (2010) Oral hypoglycemic agents vs insulin in management of gestational diabetes: a systematic review and metaanalysis. Am J Obstet Gynecol 203: 457 e451–459.
    1. Kirpichnikov D, McFarlane SI, Sowers JR (2002) Metformin: an update. Ann Intern Med 137: 25–33.
    1. Glueck CJ, Goldenberg N, Pranikoff J, Loftspring M, Sieve L, et al. (2004) Height, weight, and motor-social development during the first 18 months of life in 126 infants born to 109 mothers with polycystic ovary syndrome who conceived on and continued metformin through pregnancy. Hum Reprod 19: 1323–1330.
    1. Rowan JA, Rush EC, Obolonkin V, Battin M, Wouldes T, et al. (2011) Metformin in gestational diabetes: the offspring follow-up (MiG TOFU): body composition at 2 years of age. Diabetes Care 34: 2279–2284.
    1. Slagle M (2002) Diabetes mellitus. Medication update. South Med J 95: 50–55.
    1. Viollet B, Guigas B, Sanz Garcia N, Leclerc J, Foretz M, et al. (2012) Cellular and molecular mechanisms of metformin: an overview. Clin Sci (Lond) 122: 253–270.

Source: PubMed

Sponsorit ja yhteistyökumppanit

Sairaudet

Huumeiden interventiot

3
Tilaa