Diabetes: Pharmacological Agents

The American College of Obstetricians and Gynecologists (ACOG) recommend testing for overt diabetes at the first prenatal visit in overweight or obese women (BMI ≥25 kg/m² or ≥23 kg/m² in Asian Americans) with additional risk factors [1,2].

Diagnosis of Overt Diabetes [1]

• Fasting plasma glucose (FPG) ≥ 7 mmol/L (126 mg/dL) OR
• Hemoglobin A1C ≥ 6.5% OR
• Random plasma glucose ≥ 11.1 mmol/L (200 mg/dL) with symptoms of hyperglycemia or hyperglycemic crisis (confirm with FPG or A1C) OR
• 2-hour plasma glucose ≥ 11.1 mmol/L (200 mg/dL) during a 75 g OGTT (WHO method); confirm on repeat testing if equivocal.

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

“If a patient has discordant results from two different tests, then the test result that is above the diagnostic cut point should be repeated…” [1]

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ADA recommends women diagnosed with diabetes in the first trimester be classified as having preexisting pregestational diabetes.

IADPSG (2016) statement notes use of fasting glucose ≥5.1 mmol/L (91.8 mg/dL) to identify GDM in early pregnancy is not justified by current evidence; insufficient data exist to recommend OGTT cutoffs prior to ~20 weeks [3].

USPSTF recommends screening all pregnant women not known to have diabetes for GDM at or beyond 24 weeks [4].

• Insulin is the preferred medication for treating hyperglycemia in pregnant women because it does not cross the placenta; oral agents cross the placenta and lack long-term safety data [2,5].
• Regular insulin, insulin lispro, aspart, NPH, insulin glargine, and insulin detemir are acceptable for use in pregnancy [2].
• For women with GDM who refuse insulin, cannot safely administer insulin, or cannot afford insulin, ACOG advises metformin (and rarely glyburide) may be a reasonable alternative [2].

Insulin

Insulin is an anabolic hormone (molecular weight ~5808 Da). Maternal insulin does not cross the placenta unless bound to IgG antibody [7]. Synthetic “human” insulin is manufactured using recombinant DNA technology. U-100 insulin contains 100 units/mL.

Regular insulin and NPH are commonly used. Rapid-acting analogs (aspart, lispro) and basal analogs (detemir, glargine) have altered onset/duration profiles. Allergy to recombinant human insulin is uncommon and may relate to components such as zinc, protamine, and meta-cresol [8].

Compared with regular insulin, rapid-acting analogs (lispro/aspart) show better postprandial control, less postprandial hypoglycemia, and a trend toward reduction of preterm delivery. ACOG recommends rapid-acting analogs as preferred over regular insulin for pregnancy [2]. Among the potential clinical adverse effects associated with the use of all insulins are hypoglycemia and hypokalemia.

Administration

When mixing longer-acting insulin (e.g., NPH) with short/rapid acting (e.g., regular), draw up the short/rapid acting insulin first. Insulin glargine must not be diluted or mixed with other insulin/solutions. Abdominal subcutaneous tissue often provides more consistent absorption [13].

Storage

Unopened insulin: 2–8°C (36–46°F); do not freeze. After initial use, a vial may be kept below 30°C (86°F) for up to 28 days; avoid heat/sunlight. Pump reservoir insulin should be discarded at least every 48 hours or after exposure to >37°C (98.6°F).

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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/

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Rapid-acting Insulins (Onset ~15 minutes)

Insulin aspart (NovoLog® — DailyMed)

Insulin lispro (Humalog® — DailyMed)

Insulin analogs. Onset ~1–15 minutes, peak 1–2 hours, duration 4–5 hours [2,6].

• Indication: control of hyperglycemia in diabetes mellitus.
• Give calculated dose subcutaneously ~15 minutes before a meal.

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

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Short-acting Insulins (Onset 30–60 minutes)

Regular insulin human injection, USP
Humulin® R — DailyMed, Novolin® R — DailyMed

Onset 30–60 minutes, peak 2–4 hours, duration 6–8 hours [2,6].

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Intermediate-acting Basal Insulin

NPH human insulin (isophane suspension)
Humulin® N — DailyMed, Novolin® N — DailyMed

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Long-acting Basal Insulin

Insulin glargine
Lantus® — DailyMed

Insulin detemir
Levemir® — DailyMed

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Continuous Subcutaneous Insulin Infusion (CSII) — Insulin Pump [12]

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

Diabetic Ketoacidosis -Orderset

See Diabetic Ketoacidosis (DKA) in Pregnancy — Inpatient Order Set (Example)

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

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Metformin (Glucophage®)

DailyMed: Metformin (example label)

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

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.

Baseline serum creatinine should be obtained before beginning metformin in women suspected of havig reanal disease or long standng diabees.. Metformin is contraindicated in renal disease or renal dysfunction When used to treat polycystic ovary syndrome and induce ovulation, metformin should be discontinued once pregnancy has been confirmed [1].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 [13-17]  

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Glyburide (Micronase®)

DailyMed: Glyburide (Micronase® label)

 Oral blood-glucose-lowering drug of the sulfonyl- urea class . Glyburide stimulates release of of insulin from the pancreas .

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 [2].

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 increased incidence of neonatal hypoglycemia [2]

(1.25, 2.5, and 5 mg tablets)

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