This document discusses the pharmacological management of diabetes during pregnancy. It recommends discontinuing statins and ACE inhibitors/ARBs prior to or as soon as pregnancy is determined due to risks to the fetus. For dyslipidemia and hypertension, lifestyle modifications and alternative medications like calcium channel blockers are suggested. Insulin is indicated if blood glucose levels cannot be controlled through diet and exercise alone, with human insulin or rapid-acting analogues seen as safe options. Metformin may be used but more studies are needed on effects, while other oral hypoglycemic agents are not recommended due to lack of data.

1. Pharmacological
Management
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2. Objectives
Discuss the safety of continuing pre-pregnancy
medications
Decide when antihyperglycemic medication is
required during pregnancy
Determine what antihyperglycemic medication to
use
Discuss initial dosing and adjustment of dose
Discuss insulin administration, storage
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3. Lipids and Blood pressure
Statins must be stopped
 Preferably prior to pregnancy or
 As soon as pregnancy determined
ACE inhibitors and ARBs (angiotensin II
receptor blockers) must be stopped
 Preferably prior to pregnancy or
 As soon as pregnancy determined
ACEI/ ARBs may cause renal failure in the
fetus
CDA, 2013
Kitzmiller, Block et al, 2008 3

4. Replacements
Dyslipidemia
 Reduction of saturated fat intake, no trans fat intake,
cholesterol intake < 200mg/day
 Weight control
 Physical activity
Hypertension
 Reduce salt intake
 Calcium channel blockers, labetalol, hydralazine and
methyldopa.
CDA, 2013
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5. Triglycerides
Triglycerides may double by 20 weeks
Cholesterol, LDL and HDL may increase 10-20%
Initiate treatment if triglycerides over 1000mg/dl
 Intensive glycemic control
 Fish oil supplement
Fibrates and niacin are best avoided during pregnancy
Goldenberg, Benderly, Goldbourt, 2008
Kitzmiller, Block et al, 2008 5

6. Insulin
Indicated when target blood glucose levels not
attained with diet and physical activity after 2 weeks
Human insulin should be used – less transfer of insulin
antibodies
Rapid acting insulin analogues (lispro and aspart)
have been shown to be safe in pregnancy
 Improve postprandial levels
 Lower risk of postprandial hypoglycemia
Fetal outcomes the same with human insulin (soluble)
or rapid acting analogues
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7. Insulin
Long acting insulin analogues
• detemir has been approved for use in pregnancy
• glargine has not yet been approved
Few studies on safety of long acting analogues in
pregnancy
Usual recommendation is to use NPH or detemir
as basal insulin
Premix insulins are an alternative but lack the
flexibility of a basal bolus regimen
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8. Starting insulin in GDM
If fasting high – start NPH or detemir at bedtime
If postprandial high – start soluble or rapid acting
before meal.
 Start with 4 units
 Titrate 1-2 units/every 2 days until targets are reached
Educate
 Administration
 Storage
 Hypoglycemia
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9. 9

10. 10

11. Insulin Syringe
• Correct syringe must be used for the
strength of the insulin
• if using 100u/1 ml insulin then must have a
100u/1ml syringe,
• if using 40u/1ml insulin must have a 40u/1ml
syringe.
• Usually disposable – intended for 1 use
only
• Insulin pens are convenient alternatives to
syringes but are more expensive
• Easier to teach
• Fewer mistakes with dosages
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12. 12

13. Insulin Practicalities
Storage
• One month at room temperature once the vial has been opened or
kept in fridge
• Must never be frozen
• Store away from source of heat
• If refrigerator not available, store in clay pot
• May be damaged by direct sunlight or vigorous shaking
• Pre-drawn syringes can be kept for one month in fridge (provided
power supply reliable)
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14. Precautions
• Insulin strength may vary (U40, U100)
• Ensure the syringe matches the strength!
• Clear insulins
• Long acting insulin analogues
• Regular/soluble insulin
• Rapid acting insulin analogues
• Cloudy insulin (should not be used if clumps do not
dissolve on mixing
• NPH or N
• Premixed insulin
• Identify and differentiate insulin type
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15. 15

16. Glucose lowering medications
Sulfonylurea – glibenclamide (glyburide)
 Minimal transfer across the placenta
 Not associated with neonatal hypoglycemia
 Must be balanced with meals and snacks to prevent
hypoglycemia
 Higher incidence of pre-eclampsia
Good control achieved…but
Jacobson et al . 2005
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17. However…
Latest evidence suggests:
 glibenclamide is associated with worse
outcomes compared to insulin and metformin
Need more studies in this area
Hence glibenclamide is not recommended in the
routine management of GDM
Feig, Moses, 2011
Balsells et al, 2015 17

18. Glucose lowering medications
Metformin
 Does cross the placenta
 Does not appear to have adverse effects on the fetus
 May be used in polycystic ovarian syndrome to improve
fertility and decrease spontaneous abortion rate
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19. Metformin vs Insulin (MiG Trial)
Neonatal complications did not vary between the 2 subject groups.
• Less severe hypoglycemia in the infants of mothers on metformin.
• Women on metformin gained less weight
• Preterm birth was more common in the metformin group, but there
was no increase in other complications.
• 76% of women who used metformin were more likely to say they
would use metformin in a subsequent pregnancy than were women
on insulin (27.2%).
46.3% of women on metformin had to be on supplemental insulin as
well.
The conclusion of this study was that metformin
was a safe option for GDM, and it was more
agreeable to the patient.
Rowan Hague Gao et al. 2008
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20. However…
What is the effect on the babies?
Unknown as to whether the use of metformin
during pregnancy is
 Beneficial
 Neutral
 Deleterious
Need more studies in this area
Metformin is therefore not recommended as a first
line therapy for GDM
Feig, Moses, 2011
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21. Other oral agents
There is insufficient data on the use of other
antidiabetic agents such as
• meglitinides,
• alpha glucosidase inhibitors,
• thiazolidinediones,
• GLP-1 agonists and DPP-4 inhibitors
The use of these agents in pregnancy cannot
be recommended
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22. Final word on oral agents
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If a woman is on oral agents when diagnosed with
GDM
-Discontinue them
-Start diet and exercise plan
-Monitor blood glucose
-Start insulin

23. References
Canadian Diabetes Association Clinical Practice Guidelines Expert Committee. Canadian Diabetes Association 2013
Clinical practice guidelines for the prevention and management of diabetes in Canada; Diabetes and pregnancy. Can J
of Diabetes. 2013;37(suppl 1):S168-183.
Feig DS, Moses RG. Metformin during pregnancy. Diabetes Care. 2011;34:2329
Goldenberg I, Benderly M, Goldbourt U. Update on the use of fibrates: focus on bezafibrate. Vasc Health Risk Manag.
2008 February;4(1):131–141.
Jacobson et al - Comparison of glyburide and insulin for the management of gestational diabetes in a large managed
care organization, American Journal of Obstetrics and Gynecology 2005
Kitzmiller JL, Block JM, Catalano PM, et al. Managing preexisting diabetes for pregnancy: Summary of evidence and
consensus recommendations for care. Diabetes Care. 2008;31(5):1060-1079.
Rowan JA, Hague WM, Gao W. et al. Metformin versus Insulin for the Treatment of Gestational Diabetes. NEJM
2008;358:2003-15
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