Diabetes Mellitus Pharmacotherapy

HbA1c and Corresponding Average Glucose

5.1% (100 mg/dL), 5.8 (120), 6.5 (140), 7.2 (160), 7.9 (180), 8.6 (200)

Non-Insulin Agents

Lower A1c at most by 1% each. High-efficacy unless otherwise noted. See Management of Blood Glucose in Type 2 Diabetes Mellitus for more information.

• Metformin

  • Mechanism: Biguanide that primarily inhibits glucose production by liver

  • Safe if GFR > 30 and Cr 1.5 or less

  • Reduces mortality rates and may reduce risk of cardiovascular events/death

  • Promotes weight loss as compared to thiazolidinediones and sulfonylureas

  • Continue even if patient is started on insulin

• Weight loss and decreased cardiovascular morbidity/mortality

  • SGLT-2 inhibitors: Flozins, e.g. empagliflozin

    • Intermediate efficacy

    • Contraindication: eGFR < 50

  • GLP-1 receptor agonists: Glutides, e.g. liraglutide

    • Mechanism: Stimulate insulin release and inhibit glucagon release

    • Injection, not oral

    • Black box warning: Risk of thyroid C-cell tumors

• Weight neutral: DPP-4 inhibitors: Gliptins, e.g. sitagliptin

  • Mechanism: DPP-4 inhibitors GLP-1 (inhibiting the inhibiting enzyme stimulates insulin release and inhibits glucagon release)

  • Intermediate efficacy

• Weight gain: Low cost medications

  • Thiazolidinediones

    • Mechanism: Improve peripheral insulin sensitivity

    • Glitazones, e.g. pioglitazone

    • High efficacy, low risk for hypoglycemia

    • Pioglitazone reduces non-fatal acute MI, stroke, and all-cause mortality

    • Black box warning: Increases fluid retention and may exacerbate heart failure; contraindicated in NYHA classes III and IV

  • Sulfonylurea

    • Mechanism: Stimulate insulin secretion from pancreatic beta cells

    • E.g glipizide and “irides”

    • Risk for hypoglycemia, especially when combined with other agents

Agents shown to reduce major adverse cardiovascular events/mortality

• Metformin

  • Black box warning: Lactic acidosis (~5 cases per 100,000 patients per year)

  • Start 500 mg qd and increased dose by 500 mg increments every 4 weeks until reaching goal of 1,000 mg BID

• Empagliflozin (Jardiance)

  • Counsel patient about increased risk for UTIs and pancreatitis.

  • 10 mg once daily; may increase to 25 mg once daily as tolerated

• Liraglutide (Victoza)

  • Start 0.6 mg subQ injections once daily for one week

  • Each week, increase daily dose by 0.6 mg if blood sugar not controlled (i.e. week 1 = 0.6 mg daily, week 2 = 1.2 mg daily, etc.)

  • Maximum dose: 3 mg once daily

Insulin

Insulin Pharmacokinetics

• Basal: Physiologic rate of basal insulin production in a non-diabetic patient = 24 units/hour

  • Glargine: Onset 2 hours, no peak, duration 20-24 hours

  • Detemir: Onset 2 hours, peak 3-9 hours, duration 6-24 hours

• NPH: Onset 2 hours, peak 4-12 hours, duration 12 hours

• Rapid acting analogs

  • Examples: Lispro, aspart

  • Onset 3-15 minutes, peak 45-75 minutes, duration 2-4 hours

Switching Basal Insulin to NPH

• NPH BID dose = [(basal insulin)*0.8]/2

• Example

  • Glargine dose = 20 units daily

  • NPH dose = [(20 units)*0.8]/2 = 8 units BID

Rapid Acting Insulin Calculations

• Sensitivity

  • Default: 1 unit insulin = ↓ 40 mg/dL blood glucose. Example: Fingerstick glucose (FSG) 280 mg/dL → 2 units lispro administered → 200 mg/dL after 4 hours.

  • Individual patient sensitivity is calculated based on response (see example below):

    • FSG 280 mg/dL → 2 units rapid acting analog → 240 mg/dL after 4 hours

    • FSG decrease = 280 mg/dL - 240 mg/dL = 40 mg/dL

    • Sensitivity = (40 mg/dL)/(2 units rapid acting analog) = 20

• Insulin:Carb Ratio

  • Default = 1:10

  • Calculated = sensitivity/4

  • Example: Sensitivity = 20, therefore insulin:carb = 20/4 = 1:5

• Rapid acting insulin pre-meal dose = (expected mealtime carbohydrate)/(insulin:carb ratio)

  • 1 piece of bread = 15g and patient plans to eat 4 pieces of toast = 60g carbohydrate

  • Insulin:carb = 1:5

  • 60g carbohydrate/5 = 12 units rapid acting insulin