Diabetes: Pharmacological Agents

FOR USE BY MEDICAL PROFESSIONALS. This page is an educational reference. The prescribing clinician must review full product labeling (DailyMed) and relevant medical literature prior to use. Insulin is generally preferred in pregnancy; oral agents cross the placenta and long-term safety data are limited.

Resources

Calculators / tools

Classification of Diabetes

  • Type 1 diabetes (T1DM): autoimmune beta-cell destruction → inability to produce insulin; predisposition to ketoacidosis.
  • Type 2 diabetes (T2DM): insulin resistance with beta-cell dysfunction → inadequate insulin secretion.
  • Other specific causes: e.g., cystic fibrosis, drug-induced (glucocorticoids).
  • Gestational diabetes (GDM): diabetes diagnosed in 2nd/3rd trimester not clearly overt before pregnancy.

Overt Diabetes in Early Pregnancy

ACOG recommends testing for overt diabetes at the first prenatal visit in overweight/obese women (BMI ≥25 kg/m2 or ≥23 kg/m2 in Asian Americans) with additional risk factors.

Diagnosis of overt diabetes (summary)

  • Fasting plasma glucose (FPG) ≥ 126 mg/dL (7.0 mmol/L) OR
  • Hemoglobin A1C ≥ 6.5% OR
  • Random plasma glucose ≥ 200 mg/dL (11.1 mmol/L) with symptoms (confirm with FPG or A1C) OR
  • 2-hour plasma glucose ≥ 200 mg/dL (11.1 mmol/L) during 75 g OGTT (confirm on repeat testing if equivocal).

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

Diagnosis of GDM

ACOG/ADA support either 1-step or 2-step testing approaches.

1-step

2-step

Self-monitoring of Blood Glucose

ACOG and ADA commonly recommend fasting and either 1-hour or 2-hour postprandial checks initially; frequency may be individualized once controlled.

Targets (ACOG / ADA)

  • Fasting ≤ 95 mg/dL (5.3 mmol/L) AND EITHER
  • 1-hour postprandial ≤ 140 mg/dL (7.8 mmol/L) OR
  • 2-hour postprandial ≤ 120 mg/dL (6.7 mmol/L)
Example prescription (test strips) Name of Blood Glucose Strip • Use 4–10 strips/day • #200 • Refills: 6 months • “Patient is pregnant”

Women with pregestational diabetes should check urine ketones if glucose routinely exceeds ~200 mg/dL and report positive results promptly.

Treatment (overview)

  • Preferred Insulin is generally preferred in pregnancy and does not cross the placenta (except when IgG-bound).
  • Regular insulin, lispro, aspart, NPH, glargine, and detemir are commonly used/considered acceptable in pregnancy.
  • Alternatives If insulin is declined or not feasible, metformin (and in limited scenarios glyburide) may be considered with counseling.

Insulin

First-line U-100 common Maternal insulin does not cross the placenta unless IgG-bound. Review hypoglycemia/hypokalemia risks and injection technique.
How administered
Subcutaneous injection (vial/syringe or pen); continuous subcutaneous insulin infusion (pump). Some formulations are IV in specific settings (e.g., DKA protocols).
How supplied
Commonly 100 units/mL (U-100) in 10 mL vials and/or 3 mL pens/cartridges (product dependent).
Practical administration notes
  • If mixing NPH with short/rapid acting insulin, draw up the short/rapid acting insulin first.
  • Do not dilute or mix insulin glargine with other insulins/solutions.
  • Abdominal subcutaneous tissue often provides more consistent absorption.
Storage (summary)
Unopened insulin: 2–8°C; do not freeze. After first use, many vials/pens may be stored at room temperature per label (often ~28 days). Avoid heat/sunlight. Pump reservoir insulin: commonly discard at least every 48 hours or after heat exposure.
Graph illustrating onset and duration of action for various insulins

Rapid-acting analogs (lispro/aspart) often provide improved postprandial control versus regular insulin; many obstetric protocols prefer rapid-acting analogs for meals.

Rapid-acting (meal) insulins

Meal coverage Typical onset ~15 minutes; duration ~4–5 hours (product dependent).

Insulin aspart
Insulin lispro
How administered
Subcutaneous injection (often ~0–15 minutes before meals per label/protocol) or via pump.
How supplied
Typically U-100 in vials, cartridges, or pens (see label).

Short-acting (regular) insulin

Older meal option Typical onset 30–60 minutes; longer duration than rapid-acting analogs.

DailyMed
How administered
Subcutaneous; IV in selected inpatient protocols (e.g., DKA) per institutional guideline.
How supplied
Typically U-100 vials (and sometimes other presentations); see label.

Intermediate-acting basal insulin (NPH)

DailyMed
How administered
Subcutaneous injection; can be mixed with short/rapid acting insulins (follow mixing technique).
How supplied
Typically U-100 vials and/or pens (see label).

Long-acting basal insulins

Insulin glargine
Insulin detemir
Administration notes
Do not mix glargine with other insulins/solutions. Basal dosing schedules vary (often once daily; sometimes split per protocol/patient factors).
How supplied
Typically U-100 vials and/or pens (see label).

Syringes

Supplies Syringe/needle selection impacts comfort and dosing accuracy.

Barrel sizes
1 mL (100 units), ½ mL (50 units), 3/10 mL (30 units).
Needle examples
  • BD Micro-Fine™ IV Needle: 28G, 12.7 mm (1/2")
  • BD Ultra-Fine™ Needle: 30G, 12.7 mm (1/2")
  • BD Ultra-Fine™ Short: 31G, 8 mm (5/16")
Pen needles
Common gauges: 29G, 31G, 32G. Lengths: 4, 5, 6, 8, 12.7 mm.
Example Rx
Syringe Size: 1 cc, ½ cc, 1/3 cc, or 1/3 cc with half-unit scale
Needle: 31G, 8 mm (5/16")
Sig: 4 syringes/day • #100 • Refills: 6 months
Sharps disposal

Continuous Subcutaneous Insulin Infusion (CSII) — Insulin Pump

Link Use your existing calculators/protocols for initial settings and conversions.

Diabetic Ketoacidosis (DKA) — Order Set

Emergency DKA in pregnancy is time-sensitive; treat per institutional protocol.

Oral Hypoglycemic Agents

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

Metformin (Glucophage®)

Alternative Biguanide; decreases hepatic glucose production and improves insulin sensitivity.

How administered
Oral tablets (immediate-release and extended-release forms exist; verify product).
Typical dosing (legacy text)
500 mg once or twice daily with meals; may increase by 500 mg every 3–7 days up to ~2500 mg/day (product/patient dependent).
Key precautions
Obtain baseline renal function when renal disease is suspected; contraindicated in significant renal dysfunction per labeling. Discontinue prior to major surgery or iodinated contrast studies per protocol/label. If used for PCOS/ovulation induction, discontinue once pregnancy is confirmed (per referenced guidance).
How supplied
Tablets in common strengths (e.g., 500/850/1000 mg) and extended-release variants (see label).
DailyMed
Breastfeeding (legacy)
Milk levels are low; infants receive <0.5% of maternal weight-adjusted dose. Use caution in premature infants and infants with renal disease.

Glyburide (Micronase®)

Rarely used Sulfonylurea; stimulates pancreatic insulin secretion. Associated with neonatal hypoglycemia in some comparisons vs insulin.

How administered
Oral tablets.
Typical dosing (legacy text)
Start 1.25–2.5 mg PO daily (often before meals). May titrate by 1.25–2.5 mg every 3–7 days up to 20 mg/day (protocol/patient dependent). Avoid in reported sulfa allergy (legacy note; confirm allergy specifics).
How supplied
Tablets commonly 1.25 mg, 2.5 mg, 5 mg (see label).
DailyMed
Adverse effects (summary)
Hypoglycemia; allergic reaction. Some meta-analyses report increased neonatal hypoglycemia vs insulin.
References
  1. Diagnosis and Classification of Diabetes: Standards of Care in Diabetes—2024. Diabetes Care 2024;47(Supplement_1):S20–S42.
  2. Gestational diabetes mellitus. ACOG Practice Bulletin No. 190. Obstet Gynecol 2018;131:e49–64.
  3. McIntyre HD, Sacks DA, Barbour LA, et al. Issues with the diagnosis and classification of hyperglycemia in early pregnancy. Diabetes Care 2016;39:53–4.
  4. Moyer VA. Screening for gestational diabetes mellitus: USPSTF recommendation statement. Ann Intern Med 2014;160:414–20.
  5. Management of Diabetes in Pregnancy: Standards of Medical Care in Diabetes—2019. Diabetes Care 2019;42(Suppl 1):S165–S172.
  6. Pregestational diabetes mellitus. ACOG Practice Bulletin No. 201. Obstet Gynecol 2018;132:e228–48.
  7. Menon RK, et al. Transplacental passage of insulin in pregnant women with insulin-dependent diabetes mellitus. N Engl J Med. 1990;323(5):309–15. PMID:2195347.
  8. Ghazavi MK, Johnston GA. Insulin allergy. Clin Dermatol. 2011;29(3):300–5. PMID:21496738.
  9. Heinemann L, et al. Time-action profile of insulin glargine vs NPH insulin and placebo. Diabetes Care. 2000;23(5):644–9. PMID:10834424.
  10. Plank J, et al. Pharmacodynamic/pharmacokinetic properties of insulin detemir. Diabetes Care. 2005;28(5):1107–12. PMID:15855574.
  11. Braak EW, et al. Injection site effects on PK/PD of insulin lispro and regular insulin. Diabetes Care. 1996.
  12. Grunberger G, et al. AACE/ACE insulin pump management consensus statement. Endocr Pract. 2014;20(5):463–89. PMID:24816754.
  13. Metformin lactation references (legacy numbering retained in original page).
  14. Feig DS, et al. Transfer of glyburide/glipizide into breast milk. Diabetes Care. 2005;28:1851–5. PMID:16043722.
  15. Glatstein MM, et al. Transfer of glyburide and glipizide into breast milk. Can Fam Physician. 2009;55(4):371–3. PMID:19366943.

Reviewed by Mark A Curran, M.D., F.A.C.O.G.  • Updated formatting: 1/1/2026