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Free Patient educational Materials (brochures, food guides,  weight gain grids, etc.) available at:

  • California Diabetes and Pregnancy Program CDAPP Sweet Success Resource & Training Center
  • http://www.fda.gov/ForConsumers/ByAudience/ForWomen/WomensHealthTopics/ucm117969.htm

    Definition of Diabetes
    An abnormally high amount of sugar (glucose) in the blood . Overt diabetes may be diagnosed if any of the following criteria are present

    • Fasting* plasma glucose (FPG) greater than or equal to 7 mmol/L (126 mg/dl )
    • Hemoglobin A1 C (A1C) is 6.5% or higher,
    • Random plasma glucose greater than or equal to 11.1 mmol/L ( 200 mg/dl ) in a patent with symptoms of hyperglycemia or in hyperglycemic crisis. Should be confirmed by FPG or A1C
    • 2 hour plasma glucose greater than or equal to 11.1 mmol/L (200 mg/dL) during an 75 g OGTT as described by the WHO. Results should be confirmed on repeat testing if hyperglycemia is equivocal .

    * Fasting= no caloric intake for at least 8 hours.


    Classification of Diabetes [44]

  • Type 1 diabetes mellitus (T1DM): Inability to produce insulin caused by autoimmune destruction of pancreatic beta cells. T1DM patients have a propensity to develop ketoacidosis. Previously termed insulin-dependent diabetes or juvenile diabetes.
  • Type 2 diabetes mellitus (T2DM)   Insulin resistance in muscle and liver with beta-cell failure leading to inadequate insulin secretion . Previously termed noninsulin-dependent diabetes .
  • Other: Diabetes due to other specific causes such as cystic fibrosis or drug induced (glucocorticoids).
  • Gestational diabetes mellitus (GDM) : > Diabetes  that was not clearly overt diabetes prior to gestation diagnosed in the second or third trimester of pregnancy.


    Diagnosis of Hyperglycemia in Pregnancy

    Diagnosis of Gestational Diabetes Mellitus (GDM) [1-4]

    The American College of Obstetricians and Gynecologists (ACOG) supports NIH recommendations and recommends that before the testing approach and diagnostic criteria for GDM are changed, implications of such changes should be studied.

    1 Hour (50 g) Oral Glucose Tolerance Test
    2 Hour (75 g) Oral Glucose Tolerance Test
    3 Hour (100 g) Oral Glucose Tolerance Test


    Diet

    Key components in the management of diabetes are diet and exercise.
    Click here for diabetic exchange list.


    Self-Monitoring of Blood Glucose [1.7]

    The Ameican College of Obstetricians and Gynecologists recommends initially measuring the fasting blood sugar and either 1 or 2 hours after each meal. The frequency of the monitoring may be modified in gestational diabetes (GDM) once glucose levels have been well controlled on diet [1].

    The California Diabetes and Pregnancy Program (CDAPP): Sweet Success recommends measuring the blood sugars after fasting, premeal, one hour after start of meals, bedtime in GDM, and Type 1, Type 2 diabetes on Multiple daily Insulin Injection (MDI) or on Continuous Subcutaneous Insulin infusion (CSII). Women on insulin may occasionally also need to check blood sugar at a 3 AM blood. Women with type 2 diabetes on oral medications should test their fasting, one hour after start of meals ,and bedtime blood sugars.

    Example of a prescription for glucose test strips :

    Name of Blood Glucose Strip
    Use (4 to 10) of strips per day
    # 200 strips
    Refills: 6 months
    Patient is pregnant


    Target blood sugar ranges recommended by the ACOG and the American Diabetes Association (ADA) during pregnancy for women with GDM, type 1 or type 2 diabetes >[1, 44]
  • Preprandial less than or = 95 mg/dL (5.3mmol/L) and either One-hour postmeal less than or = 140 mg/dL (7.8 mmol/L) OR
  • Two-hour postmeal less than or = 120 mg/dL (6.7 mmol/L)

    Target blood sugar ranges recommended during pregnancy by the California Diabetes and Pregnancy Program

  • Fasting blood sugar 60 to 89 mg/dl (3.3 to 4.9 mmol/L )
  • Premeal, bedtime,overnight 60 to 99 mg/dl ( 3.3 to 5 mmol/L)
  • Postprandial 1 hour from start of meals 100 to 129 mg/dl ( 5.6 to 7.2 mmol/L )

    “Patients should check urine ketones when their glucose levels exceed 200 mg/dL and immediately report positive results to their health care teams” [33]

    The CDAPP recommends starting medical therapy when "greater than 20% of the blood glucose (BG) values in one week are out of range, or BG values are repeatedly elevated at a specific time of day and meal plan or activity cannot be modified to correct the elevated blood glucose " [7] Insulin is considered the first-line treatment for diabetes in pregnancy by the ACOG and the ADA [1,44]


    Anti-Diabetic Agents

    Insulin

    Insulin is an anabolic hormone with a molecular weight of 5808 Da. Maternal insulin does not cross the placenta unless it is bound to IgG antibody [29]. Insulin is produced in the pancreas and is secreted in response to increased blood glucose and amino acids following ingestion of a meal. Insulin signals the cells (primarily skeletal muscle) to increase their uptake of glucose, suppresses lipolysis, acts on the liver to store glucose as glycogen, and inhibits glucagon secretion thereby preventing glucagon from releasing glucose from the liver.

    Synthetic "human" insulin is manufactured using recombinant DNA technology.  Doses of insulin are measured in units. U-100 insulin contains 100 units/mL. The most commonly used types of insulin during pregnancy are regular insulin and NPH.  Neutral Protamine Hagedorn , NPH, is named after one of its developers the physician Hans Christian Hagedorn who discovered that combining a suspension of crystalline zinc insulin with protamine could prolong the duration of action of the insulin.  Insulin aspart , insulin lispro, insulin detemir, and insulin glargine are human insulin that have had their chemical composition slightly altered to influence their onset and duration of action. Allergy to recombinant human insulin preparations is uncommon , and more likely due to components including zinc, protamine, and meta-cresol [32].

    The graph below illustrates the differences in the onset and duration of action for various types of insulin.

    http://perinatology.com/images/Insulin%20Activitysm.jpg

    When compared to treatment with regular insulin, rapid-acting insulin analogs,lispro and aspart show better postprandial control, less hypoglycemia and a trend towards reduction of preterm delivery. The California Diabetes and Pregnancy Program recommends the rapid acting insulin analogs lispro and aspart, and NPH as the preferred insulins for pregnancy.  In addition, women on glargine and detemir should consider switching to intermediate acting NPH or to a continuous subcutaneous insulin pump before becoming pregnant [7].

    Administration

    In general, when a longer-acting insulin (e.g. NPH insulin isophane suspensions) is mixed with short-acting or rapid acting-soluble insulin (e.g., regular), the short-acting or rapid acting insulin should be drawn into the syringe first. Insulin glargine must NOT be diluted or mixed with any other insulin or solution The subcutaneous tissue of the abdomen is preferred site for injection because absorption of the insulin is more consistent from this location than subcutaneous tissues in other locations. [30]

    See Initial Insulin Calculator and Intensive Multiple Daily Injections (MDI)

    Among the potential clinical adverse effects associated with the use of all insulins are hypoglycemia and hypokalemia.

    Storage

    Unopened insulin should be stored in a refrigerator between 2 and 8°C (36 and 46°F); it should not be placed in a freezer. After initial use a vial may be kept at temperatures below 30°C (86°F) for up to 28 days, but should not be exposed to excessive heat or sunlight. Unused insulin should be thrown away after the expiration date. Insulin in a pump reservoir should be discarded after at least every 48 hours of use or after exposure to temperatures that exceed 37°C (98.6°F).

    Syringes

    Insulin syringes are available in three barrel sizes 1mL (100 units), ½ mL (50 units) and 3/10 mL (30 units). Needles also come in different sizes

    BD Micro-Fine™ IV Needle is a 28-gauge, 12.7mm (1/2") thin
    BD Ultra-Fine™ Needle is a 30-gauge, 12.7mm (1/2") Thinner
    BD Ultra-Fine™ Short Needle  31-gauge, 8mm (5/16") Thinnest needle

    Insulin Pen Needle sizes
    29 gauge, 31 gauge, or 32 gauge.
    Insulin Pen Needle lengths
     4, 5, 6, 8, or 12.7 mm

    Example of a prescription for syringes :

    Syringe Size: 1 cc, ½ cc, 1/3 cc, or 1/3 cc with half-unit scale
    Ultra-Fine™ Short ;Needle 31-gauge, 8mm (5/16")
    Sig: 4 of syringes used per day
    #100:
    Refills: 6 months

    For information on safe disposal of needles, syringes, and other sharps in the community contact:

    Safe Needle Disposal
    https://safeneedledisposal.org/

    California
    Sharps Waste Disposal: Household Hazardous Waste - CalRecycle
    http://www.calrecycle.ca.gov/homehazwaste/sharps/


    Rapid-acting Insulins- Onset 15 minutes

    Insulin aspart [rDNA origin] injection (NovoLog>®
    Insulin lispro, [rDNA origin] injection (Humalog®

    Insulin analogs. Onset 1 to 15 minutes , peak of action 1 to 2 hours, duration 4 to 5 hours [32]

    • Indicated in the treatment of patients with diabetes mellitus for the control of hyperglycemia. Give calculated dose subcutaneously 15 minutes before a meal.
      The algorithm below may used, but may need to be modified according to the patient population. [31]
       
      Preprandial or Bedtime Blood Glucose average for at least 3 consecutive days (mg/dl) Adjust dose of aspart (Novolog) units
      >180 +3
      160-180 +2
      140-159 +2
      120-139 +1
      100-119 maintain dose
      80-99 -1
      60-79 -2
      <60 -4

    (100 Units per mL in 10 mL vials, 3 mL cartridges, or 3 mL Pens)


    Short-acting Insulins- Onset 30 to 60 minutes

    Regular insulin human injection, USP (rDNA origin)
    Humulin ® R, Novolin® R
    Insulin. Onset 30 to 60 minutes, peak of action 2 to 3 hours, duration of action 5 to 8 hours [33].

    • Indicated in the treatment of patients with diabetes mellitus for the control of hyperglycemia.

      Give calculated dose subcutaneously 30 minutes before a meal.

    (100 Units per mL in 10 mL vials)


    Regular insulin human injection, USP (rDNA origin)
    Humulin R (U-500) ® ,Concentrated)

    Insulin. Onset 30 to 60 minutes , peak of action 2 to 4 hours, duration of action 6 to 8 hours

    • Indicated in the treatment of diabetic patients with marked insulin resistance (daily requirements more than 200 units

    Give calculated dose subcutaneously 30 minutes before a meal.

    (500 Units per mL in 20 mL vials)


    Intermediate-acting, Basal Insulin

    Neutral Protamine Hagedorn (NPH) Human Insulin (rDNA origin) Isophane Suspension
    Humulin ®N , Novolin® N )

    Zinc insulin combined with the polypeptide protamine. Onset 2 to 4 hours ,peak of action 4 to 10 hours, duration of action 10 to 16 hours

    • Indicated in the treatment of patients with diabetes mellitus for the control of hyperglycemia.

    Give calculated dose alone or mixed with short or rapid acting insulin subcutaneously.

    (100 Units per mL in 10 mL vials)


    Long-acting, Basal Insulin

    Insulin detemir [rDNA origin] injection
    Levemir ®

    Insulin .Onset 1 to 3 hours, peak of action 4 to 14 hours (no true peak), duration of action 6 to 24 hours (dose dependent)

  • Indicated in the treatment of patients with diabetes mellitus for the control of hyperglycemia. Not recommended for treating diabetic ketoacidosis.
  • Give calculated dose alone .Do not dilute or mix with any other insulin or solution. Do not administer subcutaneously via an insulin pump, intramuscularly, or intravenously.

    If converting from insulin glargine to LEVEMIR, the change can be done on a unit-to-unit basis. If converting from NPH insulin, the change can be done on a unit-to-unit basis. However, some patients with type 2 diabetes may require more LEVEMIR than NPH

    (100 Units per mL in 10 mL vials,3 mL LEVEMIR FlexTouch ® )


    Continuous subcutaneous insulin infusion (CSII) therapy- Insulin pump [34]

    The American Association of Clinical Endocrinologists (AACE) considers suitable insulin pump candidates to have the following characteristics:
    Women with type 1 Diabetes who do not reach glycemic goals despite adherence to maximum multiple daily injections of insulin especially if they have very labile diabetes , frequent severe hypoglycemia and/or hypoglycemia unawareness, significant “dawn phenomenon,” extreme insulin sensitivity , and in special populations (e.g. pregnant women , competitive athletes) or other patients who, after investigation and careful consideration, feel that CSII would be helpful in achieving and maintaining treatment targets

    Women with insulin requiring type 2 Diabetes who satisfy any or all of the following: are C-peptide positive, but with suboptimal control on a maximal program of basal/bolus injections, have substantial “dawn phenomenon”, erratic lifestyle (e.g., unpredictable schedules), OR severe insulin resistance.

    AACE also recommends "After delivery, the insulin pump infusion should be stopped temporarily to avoid hypoglycemia; once the blood glucose is >100 mg/dL, infusion should be resumed at the prepregnancy settings".

    SeeCalculation of Initial Insulin Pump settings (AACE)
    See Calculation of Initial Insulin Pump settings (Sweet Success)


    Oral Hypoglycemic Agents (OHA)

    If oral diabetes agents are used, patients should be clearly informed that these drugs cross the placenta and may have unknown risks to the fetus.

    Glyburide (Micronase® )[13].
    Oral blood-glucose-lowering drug of the sulfonyl- urea class . Glyburide stimulates release of of insulin from the pancreas .Glyburide crosses the placenta [26,27].

  • Used as an adjunct to diet to lower the blood glucose in patients withnon-insulin-dependent diabetes mellitus [1,7].
  • Starting dose 1.25 mg to 2.5 mg PO daily 60 minutes before meals to control postprandial sugar. Use lower dose for women with weight less than 200 pounds.
    May give at 10 to 11 PM to control fasting blood sugar.
    May increase by 1.25 to 2.5 mg every 3 to 7days until blood sugar controlled or a maximum daily dose of 20 mg.

    Should not be used in patients who report a sulfa allergy [1]. Potential clinical adverse effects associated with the use of glyburide are hypoglycemia and allergic reaction. Meta-analysis found when compared to insulin, glyburide was associated with higher neonatal birth weight and increased incidence of neonatal hypoglycemia [14,15]

    (1.25, 2.5, and 5 mg tablets)

    Use in Breastfeeding: Limited data indicate that the levels of glyburide in milk are negligible; Appears to be compatible with breast-feeding. However, the baby should be monitored for signs of hypoglycemia [16,17].


    Metformin (Glucophage ® )
    Oral blood-glucose-lowering drug of the biguanide class. Metformin decreases glucose production by the liver, decreases intestinal absorption of glucose, and improves insulin sensitivity by increasing peripheral glucose uptake and utilization . Metformin crosses the placenta[ 28]

    • Used as an adjunct to diet to lower the blood glucose in patients with non-insulin-dependent diabetes mellitus [14,15]. ACOG considers metformin a reasonable second-line choice for women with GDM who decline insulin therapy or for those who may not be able to safely administer insulin [1]

    500 mg once or twice daily given with meals. Usually given with breakfast and dinner. May increase in increments of 500 mg every 3 to 7 days up to a total of 2500 mg per day.

    If a woman is taking metformin prior to her pregnancy or at the first prenatal visit, the CDAPP Sweet Success Program recommends she continues to take metformin [7]. Women taking metformin for polycystic ovarian syndrome (PCOS) may benefit from continuing; to take metformin throughout the pregnancy [19,20]

    Lactic acidosis is a rare, but serious, metabolic complication that can occur due to metformin accumulation during treatment.; Metformin is contraindicated in renal disease or renal dysfunction (e.g., as suggested by serum creatinine levels or abnormal creatinine clearance), which may also result from conditions such as cardiovascular collapse (shock), acute myocardial infarction, and septicemia  Discontinue prior to major surgery, or radiological studies involving contrast materials.

    (500, 850, and 1000 mg tablets)

    Use in Breastfeeding:  Metformin levels in milk are low and infants would receive less than 0.5% of their mother's weight-adjusted dosage. Use with caution in premature infants and infants with renal disease [22-25]. REFERENCES

    Reviewed by Mark A Curran, M.D. 7/1/2017

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