Tools for Practice


#148 Has insulin met its match? Metformin for gestational diabetes


CLINICAL QUESTION
Is metformin a reasonable alternative to insulin in gestational diabetes mellitus (GDM)?

BOTTOM LINE
Compared to insulin, metformin results in 1kg less maternal weight gain and less severe neonatal hypoglycaemia for one in 22 babies, but results in earlier delivery by about one day. Other clinical outcomes are unchanged and long-term safety of metformin in GDM appears reassuring. Metformin is a reasonable option in GDM requiring treatment.  


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EVIDENCE
  • Three systematic reviews1-3 of up to six open-label, Randomized Controlled Trials (RCTs) of metformin or insulin in 1,372 women: Over half of patients from one RCT.4 
    • Metformin women had:  
      • Less weight gain (1.1kg).1  
      • Less gestational hypertension: 
        • 3.6% versus 6.8%, Number Needed to Treat (NNT)=32.2  
      • More preterm births (<37 weeks):  
        • 10.1% versus 6.7%, Number Needed to Harm (NNH)=30.2 
        • Delivered ~1 day earlier (95% Confidence Interval: 0.14–2.1 days).1 
      • No difference in caesarean section rates or obstetrical trauma.1 
    • Metformin babies had:  
      • No difference in birth weight, macrosomia, hypoglycaemia (<2.6 mmol/l), shoulder dystocia, low APGAR scores, admission to level 2 or 3 nursery or mortality.1-4 
      • Less severe hypoglycaemia (<1.6 mmol/l):  
        • 3.3% versus 8.1% NNT=22.4 
    • 77% women preferred metformin for subsequent pregnancy.4  
    • ~1/3 of metformin users eventually required insulin.1 
  • Long-term follow-up: >400 children from RCTs4,5  followed up to two years found children born to mothers on metformin (compared to insulin) had: 
    • Similar6 or clinically insignificant differences in height and weight (example ~0.7kg heavier and 1.7cm taller7) or development at 18 months.6
Context: 
  • GDM occurs in ~5% of pregnancies.8 
    • Risk factors include: Family/previous history of GDM, higher body mass index, and certain ethnicities.8,9 
  • Recent guidelines recommend either universal screening for GDM,8 or screening only those with risk factors.9 
  • For women with ‘mild’ GDM, advising mothers of diagnosis and treating (compared to not advising nor treating) reduces perinatal complications (death, shoulder dystocia, bone fracture, and nerve palsy) from 4% to 1% (NNT=34) but increases the likelihood of labour induction and admission to neonatal nursery (both NNHs=10).10 
  • Although off-label in pregnancy,11 UK guidelines9 recommend (in order) diet and exercise, then metformin, then insulin.  
October 13, 2015

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Author(s):

  • Darryl Huang MD
  • Michael R Kolber BSc MD CCFP MSc

1. Balsells M, García-Patterson A, Solà I, et al. BMJ. 2015; 350:h102.

2. Poolsup N, Suksomboon N, Amin M. PLoS ONE. 2014; 9(10):e109985.

3. Gui J, Liu Q, Feng L. PLoS ONE 2013; 8(5):e64585.

4. Rowan JA, Hague WM, Gao W, et al. N Engl J Med. 2008; 358(19):2003-15.

5. Ijäs H, Vääräsmäki M, Morin-Papunen L, et al. BJOG. 2011; 118(7):880-5.

6. Rowan JA, Rush EC, Obolonkin V, et al. Diabetes Care. 2011; 34(10):2279-84.

7. Ijäs H, Vääräsmäki M, Saarela T, et al. BJOG. 2015; 122(7):994-1000.

8. Committee on Practice Bulletins—Obstetrics. Obstet Gynecol. 2013; 122(2):406-16.

9. National Institute for Health and Care Excellence (NICE). Diabetes in pregnancy: management of diabetes and its complications from preconception to the postnatal period. Published: 25 February 2015. Available at: http://www.nice.org.uk/guidance/ng3. Last accessed: June 4, 2015.

10. Crowther CA, Hiller JE, Moss JR, et al. N Engl J Med. 2005; 352:2477-86.

11. Sanofi-aventis Canada. Product Monograph Glucophage® (Metformin Hydrochloride). October 22, 2014. Available at: www.sanofi.ca/products/en/glucophage.pdf. Last accessed: June 23, 2015.

Authors do not have any conflicts of interest to declare.