Pharmacological Management
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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 2
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
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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 4
Triglycerides Triglycerides may double by 20 weeks Cholesterol, LDL and HDL may increase 10-20%
Initiate treatment if triglycerides over 1000mg/dl ď&#x201A;§ Intensive glycemic control ď&#x201A;§ Fish oil supplement Fibrates and niacin are best avoided during pregnancy
Goldenberg, Benderly, Goldbourt, 2008 Kitzmiller, Block et al, 2008
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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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Insulin Long acting insulin analogues
â&#x20AC;˘ detemir has been approved for use in pregnancy â&#x20AC;˘ 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 7
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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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 11
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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) 13
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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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 16
Howeverâ&#x20AC;Ś Latest evidence suggests: ď&#x192;&#x2DC; 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
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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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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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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 20
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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Final word on oral agents If a woman is on oral agents when diagnosed with GDM
-Discontinue them -Start diet and exercise plan -Monitor blood glucose -Start insulin
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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):131â&#x20AC;&#x201C;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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