Pharmacological therapy Information By Diabetesasia.org

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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

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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 lt 200mg/day
• Weight control
• Physical activity
• Hypertension
• Reduce salt intake
• Calcium channel blockers, labetalol, hydralazine
  and methyldopa.

CDA, 2013
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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
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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
• 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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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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Some factors affecting absorption
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Injecting insulin
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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

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Insulin practicalities
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Insulin practicalities
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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Precautions
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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Side effects
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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 achievedbut

Jacobson et al . 2005
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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
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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
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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. 201337(suppl 1)S168-183.
• Feig DS, Moses RG. Metformin during pregnancy.
  Diabetes Care. 2011342329
• Goldenberg I, Benderly M, Goldbourt U. Update on
  the use of fibrates focus on bezafibrate. Vasc
  Health Risk Manag. 2008 February4(1)131141.
• 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. 200831(5)1060-1079.
• Rowan JA, Hague WM, Gao W. et al. Metformin
  versus Insulin for the Treatment of Gestational
  Diabetes. NEJM 20083582003-15