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Pharmacological therapy Information By Diabetesasia.org

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Our aim is to alleviate human suffering related to diabetes and its complications among those least able to withstand the burden of the disease. From 2002 to March 2017, the World Diabetes Foundation provided USD 130 million in funding to 511 projects in 115 countries. For every dollar spent, the Foundation raises approximately 2 dollars in cash or as in-kind donations from other sources. The total value of the WDF project portfolio reached USD 377 million, excluding WDF’s own advocacy and strategic platforms. – PowerPoint PPT presentation

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Title: Pharmacological therapy Information By Diabetesasia.org


1
Pharmacological Management
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

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
4
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
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
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

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

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

9
Some factors affecting absorption
10
Injecting insulin
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

12
Insulin practicalities
13
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)

14
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

15
Side effects
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 achievedbut

Jacobson et al . 2005
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
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

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
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
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

22
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

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. 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
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