Insulin Dosing & Titration

Insulin Dosing & Titration

Master insulin dosing and titration strategies with free flashcards and evidence-based protocols. This lesson covers basal-bolus regimens, correction factors, carbohydrate counting, and systematic titration algorithms—essential skills for NAPLEX success and safe diabetes management in clinical practice.

Welcome to Insulin Dosing & Titration 💉

Insulin therapy remains the cornerstone of type 1 diabetes management and is increasingly used in type 2 diabetes when oral agents fail to achieve glycemic control. As a pharmacist, you'll be expected to calculate initial insulin doses, recommend titration strategies, and troubleshoot therapy to minimize hypoglycemia while optimizing A1C reduction. This lesson provides the quantitative skills and clinical judgment frameworks you need for both exam success and patient care excellence.

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Core Concepts: Building Your Insulin Dosing Foundation 🎯

Understanding Total Daily Dose (TDD) Calculations

The Total Daily Dose (TDD) serves as the foundation for all insulin regimen calculations. Multiple methods exist for determining initial TDD:

Method	Calculation	Clinical Context
Weight-Based	0.4-1.0 units/kg/day	Most common initial approach
Conservative Start	0.2-0.4 units/kg/day	Elderly, renal impairment, insulin-naïve
Type 1 Maintenance	0.5-0.7 units/kg/day	After honeymoon period
Type 2 Insulin-Resistant	0.7-1.5 units/kg/day	Obesity, high A1C, long diabetes duration
Pregnancy	0.7-1.0 units/kg/day	Increases by trimester (up to 1.0-2.0)

💡 Key Principle: Start conservatively and titrate up. Hypoglycemia is more dangerous than temporary hyperglycemia during dose finding.

The Basal-Bolus Split: 50/50 Rule 🔄

Once TDD is determined, the standard distribution is:

TDD = Basal (50%) + Bolus (50%)
       │              │
       │              └─── Divided among meals
       │                   (breakfast, lunch, dinner)
       │
       └─── Long-acting insulin
            (glargine, detemir, degludec)

Example: 60 units TDD
├─ Basal: 30 units daily (glargine at bedtime)
└─ Bolus: 30 units total
   ├─ Breakfast: 10 units (rapid-acting)
   ├─ Lunch: 8 units (rapid-acting)
   └─ Dinner: 12 units (rapid-acting)

Alternative distributions may be used based on patient patterns:

• 40% basal / 60% bolus: For patients with significant postprandial excursions
• 60% basal / 40% bolus: For patients with elevated fasting glucose but better postprandial control

Insulin-to-Carbohydrate Ratio (I:C Ratio) 🍞

The I:C ratio determines how many grams of carbohydrate are covered by 1 unit of rapid-acting insulin.

Calculation using the "500 Rule":

I:C Ratio = 500 ÷ TDD

Example: TDD = 50 units
I:C Ratio = 500 ÷ 50 = 10

Interpretation: 1 unit covers 10 grams of carbohydrate

Clinical Application:

If a patient plans to eat 60 grams of carbohydrate:

Step	Calculation	Result
1	60 g carbs ÷ 10 g per unit	6 units needed

⚠️ Common Mistake: Using I:C ratios with long-acting insulin. I:C ratios apply ONLY to rapid-acting (bolus) insulin for meal coverage.

Insulin Sensitivity Factor (ISF) / Correction Factor 📉

The ISF (also called correction factor) predicts how much 1 unit of rapid-acting insulin will lower blood glucose.

Calculation using the "1800 Rule" (for regular insulin) or "1500 Rule" (for rapid-acting):

ISF = 1500 ÷ TDD  (for rapid-acting: lispro, aspart, glulisine)
ISF = 1800 ÷ TDD  (for regular insulin)

Example: TDD = 60 units
ISF = 1500 ÷ 60 = 25 mg/dL per unit

Interpretation: 1 unit lowers glucose by 25 mg/dL

Clinical Application:

Patient's pre-meal glucose is 220 mg/dL, target is 120 mg/dL:

Step	Calculation	Result
1	220 - 120	100 mg/dL above target
2	100 ÷ 25 (ISF)	4 units correction dose

Total pre-meal dose = Meal bolus (I:C) + Correction dose (ISF)

💡 Pro Tip: Use more conservative ISF (larger number, smaller correction) at bedtime to avoid nocturnal hypoglycemia. Some clinicians use 1800 rule for nighttime corrections even with rapid-acting insulin.

Basal Insulin Titration Algorithms 📊

Systematic titration is crucial for safety and efficacy. Multiple validated algorithms exist:

Alternative: Conservative Titration (START Protocol)

• Start with 10 units once daily (or 0.1-0.2 units/kg)
• Increase by 1 unit daily until fasting glucose 70-130 mg/dL
• If hypoglycemia occurs, reduce by 2-4 units

Timing Considerations:

• Adjust basal insulin based on fasting glucose (measures overnight control)
• Wait 3-5 days between adjustments for long-acting analogs to reach steady state
• Degludec requires 3-5 days due to ultra-long half-life; other long-acting insulins approach steady state in 2-3 days

Bolus Insulin Titration 🍽️

Bolus adjustments target postprandial glucose (measured 2 hours after meal start):

2-Hour Postprandial Glucose	Action
>180 mg/dL consistently	Increase meal bolus by 1-2 units (or 10-20%)
140-180 mg/dL	Increase by 0.5-1 unit
100-140 mg/dL	At goal, no change
<70 mg/dL	Decrease by 1-2 units (or 10-20%)

Pattern Management Approach:

• If fasting glucose elevated → adjust basal
• If pre-lunch glucose elevated → adjust breakfast bolus
• If pre-dinner glucose elevated → adjust lunch bolus
• If bedtime glucose elevated → adjust dinner bolus
• If 2-3 AM glucose elevated → may need to decrease basal or evening bolus (Somogyi effect vs dawn phenomenon differentiation)

🧠 Memory Device - "BARN": Basal for AM fasting, Rapid for Nutrition (meals)

Correction Dose Calculations: Putting It All Together 🧮

Scenario: Patient with TDD 50 units, pre-lunch glucose 280 mg/dL, planning to eat 75g carbohydrates, target glucose 120 mg/dL.

Step	Calculation	Result
1. Calculate I:C	500 ÷ 50	1:10 ratio
2. Calculate meal dose	75g ÷ 10	7.5 units (round to 8)
3. Calculate ISF	1500 ÷ 50	30 mg/dL per unit
4. Calculate correction	(280 - 120) ÷ 30	5.3 units (round to 5)
5. Total dose	8 + 5	13 units rapid-acting

⚠️ Insulin on Board (IOB): Rapid-acting insulin remains active for 3-5 hours. If the patient took a correction dose 2 hours ago, subtract residual insulin to avoid "stacking" and subsequent hypoglycemia.

IOB Adjustment Example:

• Previous correction: 4 units given 2 hours ago
• Assume 50% still active (approximation)
• IOB = 2 units
• New total dose: 13 - 2 = 11 units

Special Population Adjustments 👥

Renal Impairment (CrCl <30 mL/min):

• Reduce initial TDD by 25-50%
• Insulin clearance is reduced
• Higher hypoglycemia risk
• Consider 75% of calculated doses initially

Elderly Patients:

• Start with 0.2 units/kg/day
• Less aggressive targets (A1C 7.5-8.5%)
• Hypoglycemia awareness may be impaired
• Simplified regimens preferred (basal-only or premixed)

Hospitalized Patients (Sliding Scale vs Basal-Bolus):

• Sliding scale alone = reactive, poor glycemic control (not recommended as sole therapy)
• Basal-bolus + correctional = proactive, superior outcomes
• Target 140-180 mg/dL for most hospitalized patients
• NPO patients: give basal + correctional only (hold nutritional bolus)

Steroid-Induced Hyperglycemia:

• Primarily affects postprandial glucose
• May require 70% bolus / 30% basal distribution
• NPH at breakfast effective for morning prednisone dosing (matches steroid peak)
• Titrate rapidly as steroid effects are pronounced

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Detailed Examples: Clinical Scenarios 💊

Example 1: Initiating Basal-Bolus Insulin in Type 1 Diabetes

Patient Profile:

• 28-year-old male, newly diagnosed type 1 diabetes
• Weight: 70 kg
• A1C: 11.2%
• No complications, normal renal function

Step-by-Step Approach:

Step	Action	Calculation	Result
1	Calculate TDD	0.5 units/kg × 70 kg	35 units/day
2	Split basal-bolus	50/50 split	Basal: 17-18 units, Bolus: 17-18 units
3	Distribute bolus	Divide among 3 meals	Breakfast: 6u, Lunch: 5u, Dinner: 6u
4	Calculate I:C	500 ÷ 35	~1:14 (1 unit per 14g carb)
5	Calculate ISF	1500 ÷ 35	~43 mg/dL per unit

Regimen:

• Glargine U-100: 18 units at bedtime
• Lispro: 6 units before breakfast, 5 units before lunch, 6 units before dinner
• Correction factor: 1 unit per 43 mg/dL above 120 mg/dL (round to 1:40 for simplicity)
• I:C ratio: 1:14 (patient counts carbs and adjusts accordingly)

Follow-Up Plan:

• Check fasting glucose daily, adjust basal every 3 days using treat-to-target protocol
• Check 2-hour postprandial glucose after each meal, adjust respective bolus doses
• Expected A1C improvement: 1-2% with optimized therapy

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Example 2: Titrating Basal Insulin in Type 2 Diabetes

Patient Profile:

• 58-year-old female with type 2 diabetes on metformin 1000mg BID
• Weight: 85 kg, BMI 32
• A1C: 9.1%, fasting glucose averaging 210 mg/dL
• Starting insulin glargine

Initial Dose:

Method	Calculation	Dose
Conservative weight-based	0.2 units/kg × 85 kg	17 units
Alternative: 10 units start	Fixed dose approach	10 units

Choice: Start with 10 units glargine at bedtime (more conservative given insulin-naïve status)

Titration Log (Treat-to-Target Protocol):

Week	Average Fasting Glucose	Current Dose	Adjustment	New Dose
1	195 mg/dL	10 units	+8 units (≥180)	18 units
2	165 mg/dL	18 units	+6 units (140-179)	24 units
3	145 mg/dL	24 units	+6 units (140-179)	30 units
4	128 mg/dL	30 units	+4 units (120-139)	34 units
5	108 mg/dL	34 units	+2 units (100-119)	36 units
6	94 mg/dL	36 units	No change (at goal)	36 units

Outcome: Fasting glucose controlled on 36 units glargine daily. Continue metformin. Monitor A1C in 3 months (expected ~7.5%).

If A1C Still Elevated: Consider adding:

• GLP-1 receptor agonist (synergistic with basal insulin, promotes weight loss)
• Prandial insulin for postprandial control (if fasting controlled but A1C >7%)

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Example 3: Troubleshooting Hypoglycemia

Patient Profile:

• 45-year-old male with type 1 diabetes
• Current regimen: Degludec 30 units daily, lispro 8-10-12 units at meals
• I:C ratio 1:12, ISF 1:35
• Problem: Experiencing hypoglycemia (glucose <60 mg/dL) at 3 AM twice weekly

Diagnostic Approach:

Decision Tree for Nocturnal Hypoglycemia

    3 AM Hypoglycemia Detected
              │
              ↓
    Check bedtime glucose
              │
    ┌─────────┴─────────┐
    ↓                   ↓
Bedtime <120        Bedtime >180
    │                   │
    ↓                   ↓
Possible causes:   Possible causes:
- Basal too high   - Dinner bolus too high
- Dinner bolus     - "Somogyi effect"
  too high           (rebound from hypo)
- Late exercise    - Delayed food absorption
- Alcohol intake   - Gastroparesis

Patient Data Review:

• Bedtime glucose: 145-160 mg/dL (adequate)
• Fasting glucose: 180-220 mg/dL (elevated - suggests rebound)
• Pattern suggests Somogyi effect

Intervention:

Adjustment	Rationale	New Regimen
Reduce basal	Prevent nocturnal hypoglycemia	Degludec 27 units (10% reduction)
Reduce dinner bolus	Lessen overnight insulin effect	Lispro 10 units at dinner (from 12)
Add bedtime snack	Provide glucose substrate overnight	15g complex carb + protein

Alternative if Dawn Phenomenon (elevated fasting WITHOUT nocturnal hypo):

• Increase basal insulin
• Shift basal timing (take glargine in AM instead of PM)
• Add bedtime NPH (covers early morning hours specifically)

💡 Differentiation Tip: Set alarm for 2-3 AM glucose check. If low → Somogyi effect. If normal/high → dawn phenomenon.

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Example 4: Converting NPH/Regular to Basal-Bolus

Patient Profile:

• 62-year-old with type 2 diabetes on NPH/regular regimen
• Current: NPH 25 units before breakfast + 15 units before dinner, Regular 10 units before breakfast + 8 units before dinner
• A1C 8.4%, frequent afternoon hypoglycemia
• Patient wants more flexible meal timing

Current TDD: 25 + 15 + 10 + 8 = 58 units

Conversion Strategy:

Current Regimen	Type	Units	New Regimen	Units
NPH (breakfast)	Intermediate	25	Glargine (once daily)	36 (reduce 10% for safety)
NPH (dinner)	Intermediate	15
Regular (breakfast)	Short-acting	10	Lispro (breakfast)	10
Regular (lunch)	-	0	Lispro (lunch)	6 (add for coverage)
Regular (dinner)	Short-acting	8	Lispro (dinner)	8
Total		58	Total	60

New Regimen:

• Glargine U-100: 36 units at bedtime
• Lispro: 10 units before breakfast, 6 units before lunch, 8 units before dinner
• I:C ratio: 500 ÷ 60 = 1:8
• ISF: 1500 ÷ 60 = 1:25

Expected Improvements:

• ✅ Reduced afternoon hypoglycemia (NPH peak eliminated)
• ✅ More predictable basal coverage
• ✅ Flexible meal timing (can skip/delay lunch with dose adjustment)
• ✅ Better fasting glucose control

Monitoring: Check glucose before meals and bedtime for first week, adjust based on patterns.

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Common Mistakes to Avoid ⚠️

1. Using Body Weight Instead of Actual Weight for Obese Patients

❌ Wrong: 150 kg patient, use 0.5 units/kg → 75 units TDD (excessive!) ✅ Right: For BMI >30, consider using adjusted body weight or starting conservatively at 0.3-0.4 units/kg

2. Forgetting to Reduce Insulin with Weight Loss

• GLP-1 agonists, SGLT2 inhibitors, and lifestyle changes cause weight loss
• Insulin requirements decrease (approximately 1-2 units per kg lost)
• Failure to reduce = hypoglycemia risk
• Action: Reduce TDD by 10-20% when initiating weight loss medications

3. Adjusting Insulin Based on Single Glucose Reading

❌ Reacting to one high reading ✅ Look for patterns over 2-3 days before adjusting (except for hypoglycemia - react immediately)

4. Ignoring Insulin Stacking (IOB)

• Giving correction doses <3-4 hours apart
• Results in cumulative effect and delayed hypoglycemia
• Solution: Use smart insulin pens or pumps that calculate IOB automatically, or subtract ~50% of previous dose if <3 hours

5. Not Accounting for Renal Function Changes

• Insulin clearance reduced in CKD
• eGFR <60: Consider 25% dose reduction
• eGFR <30: Consider 50% dose reduction
• Monitor closely during acute kidney injury

6. Confusing I:C Ratio and ISF

• I:C = for meals (proactive dosing)
• ISF = for correction (reactive dosing)
• Never use ISF to calculate meal coverage!

7. Overlooking Injection Technique Issues

• Lipohypertrophy from repeated same-site injections → erratic absorption
• Injecting into muscle → faster absorption, hypoglycemia risk
• Education: Rotate sites, use appropriate needle length (4-6mm for most adults)

8. Inappropriate Bedtime Dosing

• Giving large correctional doses at bedtime → nocturnal hypoglycemia
• Safer approach: Use more conservative ISF at bedtime (e.g., 1800 rule instead of 1500 rule)
• Consider holding correction if glucose <180 mg/dL at bedtime

9. Not Adjusting for Activity Level

• Exercise increases insulin sensitivity for 24-48 hours
• Anticipated vigorous exercise: reduce bolus by 25-50% before activity
• Unexpected exercise: consume 15-30g carbs per 30-60 min moderate activity

10. Sliding Scale as Monotherapy in Hospitalized Patients

• Reactive approach, poor glycemic control
• Increases length of stay and complications
• Best practice: Basal + nutritional + correctional insulin (three-component approach)

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Key Takeaways 🎓

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NAPLEX-Style Problem-Solving Framework 🔍

For exam questions involving insulin dosing:

1. Identify the question type:

   • Initial dose calculation?
   • Titration/adjustment?
   • Troubleshooting hypoglycemia/hyperglycemia?
   • Conversion between regimens?

2. Gather key data:

   • Patient weight
   • Diabetes type (type 1 = needs basal + bolus; type 2 = may start basal only)
   • Renal function
   • Current glucose patterns
   • Current insulin doses (if applicable)

3. Apply appropriate formula:

   • TDD calculation
   • I:C ratio (500 rule)
   • ISF (1500 or 1800 rule)
   • Split basal-bolus

4. Consider special circumstances:

   • Renal impairment → reduce dose
   • Elderly → conservative dosing
   • Steroid use → increase bolus proportion
   • Hospital setting → basal-bolus-correctional, not sliding scale alone

5. Verify answer makes sense:

   • Typical TDD range: 20-100 units for most patients
   • I:C ratio typically 1:5 to 1:20
   • ISF typically 20-80 mg/dL per unit
   • Doses outside these ranges warrant double-checking

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📚 Further Study Resources

1. American Diabetes Association Standards of Care - Annual updates on insulin management guidelines and target glycemic ranges https://diabetesjournals.org/care/issue/47/Supplement_1

2. AACE Consensus Statement on Insulin Therapy - Comprehensive algorithms for insulin initiation and titration in type 2 diabetes https://www.aace.com/disease-and-conditions/diabetes/clinical-practice-guidelines-treatment-algorithms

3. Insulin Dosing Calculator Tools - Interactive calculators for I:C ratios, ISF, and correction doses with clinical scenarios https://www.diabetesnet.com/diabetes-tools/insulin-dosing-calculator

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🎯 You're now equipped with the quantitative skills and clinical reasoning frameworks for insulin dosing success on the NAPLEX and in practice! Master these formulas, understand the physiologic principles behind them, and always prioritize patient safety through conservative initial dosing and systematic titration. Remember: it's easier to increase insulin than to treat severe hypoglycemia.