Insulin Therapy: Comprehensive Overview

Types of Insulin and Their Characteristics

Insulin therapy encompasses multiple formulations with distinct pharmacokinetic profiles, ranging from ultra-rapid-acting analogs to long-acting basal insulins, each designed to address specific glycemic patterns throughout the day. 1

Rapid and Ultra-Rapid-Acting Insulins (Prandial/Bolus)

Insulin lispro, aspart, and glulisine: Onset 5-15 minutes, peak 1-2 hours, duration 3-5 hours 1
Administration: Given 0-15 minutes before meals to control postprandial glucose excursions 2, 1
Ultra-rapid-acting analogs (URAA): Even faster onset than traditional rapid-acting, useful for automated insulin delivery systems 1
Regular (short-acting) insulin: Onset 30 minutes, peak 2-4 hours, duration 6-8 hours; less expensive alternative but requires 30-minute pre-meal timing 1

Intermediate-Acting Insulin

NPH (Neutral Protamine Hagedorn): Onset 1-2 hours, peak 4-6 hours, duration 12-18 hours 1
Specific indication: Preferred for steroid-induced hyperglycemia due to matching daytime hyperglycemic pattern 3
Disadvantage: Higher hypoglycemia risk, particularly nocturnal, compared to long-acting analogs 1, 2

Long-Acting Basal Insulins

Insulin glargine and detemir: Duration 18-24 hours, relatively peakless profile 1, 4
Insulin degludec: Ultra-long duration (>42 hours), most stable basal coverage 5
Advantages: Lower hypoglycemia risk versus NPH, more predictable absorption 2, 4

Premixed/Co-Formulation Insulins

Fixed ratios of basal and prandial insulin (e.g., 70/30,75/25) 1
Use: Simplified regimen for patients requiring both basal and prandial coverage 2
Limitation: Less flexibility in dose adjustment, fixed meal timing required 1

Indications for Insulin Therapy

Type 1 Diabetes

All patients with type 1 diabetes require insulin as primary treatment from diagnosis. 2

Initial regimen: Multiple daily injections (MDI) with basal plus prandial insulin at diagnosis 2
Target HbA1c: <7.5% (<58 mmol/mol) for all children and most adults 2
Glucagon prescription: Mandatory for all type 1 diabetes patients due to hypoglycemia risk 1

Type 2 Diabetes

Insulin should be initiated when HbA1c ≥7.5% (≥58 mmol/mol) despite optimal use of other agents, and is essential when HbA1c ≥10% (≥86 mmol/mol). 2

Specific Indications:

Acute illness or surgery requiring tight glycemic control 2
Pregnancy in diabetes 2
Glucose toxicity (symptomatic hyperglycemia, weight loss) 1
Contraindications to or failure of oral/injectable non-insulin agents 2, 6
Immediate initiation: When blood glucose ≥300-350 mg/dL or HbA1c ≥10-12%, especially if symptomatic 5

Administration Techniques

Injection Site Selection and Rotation

Insulin must be injected subcutaneously, never intramuscularly, to ensure predictable absorption. 1

Approved sites: Abdomen (fastest absorption), thigh, buttock, upper arm 1
Absorption hierarchy: Abdomen > arms > thighs > buttocks 7
Site rotation protocol: Systematic rotation within one anatomical area rather than between different areas to prevent erratic absorption 5, 7
Lipohypertrophy avoidance: Rotate sites to prevent fat accumulation that causes unpredictable absorption and glycemic variability 1

Needle Selection

4-mm pen needles should be first-line choice for all patients as they are safe, effective, less painful, and minimize intramuscular injection risk. 2

Longer needles (≥6 mm): Increased risk of intramuscular delivery, especially in lean patients and children 1, 2
Injection angle: 90-degree angle for subcutaneous administration with appropriate needle length 5
Needle reuse: Not recommended by manufacturers; associated with lipohypertrophy risk 2

Insulin Mixing

NPH insulin: Requires gentle rolling (not shaking) to resuspend before administration 7
Analog insulins: Clear solutions requiring no mixing 1
Compatibility: Regular insulin can be mixed with NPH; long-acting analogs should not be mixed 1

Insulin Regimens and Initiation Strategies

Type 1 Diabetes Regimens (in order of preference)

Automated insulin delivery (hybrid closed-loop) systems provide the highest flexibility and lowest hypoglycemia risk, representing the optimal regimen when accessible. 1

Hybrid closed-loop technology: Highest flexibility, lowest hypoglycemia, highest cost 1
Insulin pump with predictive low-glucose suspend: High flexibility and safety 1
MDI with long-acting analog + rapid/ultra-rapid analog: 40-60% basal, remainder as prandial 1
MDI with NPH + rapid-acting analog: Less preferred due to hypoglycemia risk 1
Twice-daily NPH + regular insulin: Least flexible, highest hypoglycemia risk, lowest cost 1

Type 2 Diabetes Initiation

Begin with basal insulin at 10 units daily or 0.1-0.2 units/kg/day, continuing metformin for ongoing metabolic benefits. 1, 5

Basal Insulin Initiation Protocol:

Starting dose: 10 units/day OR 0.1-0.2 units/kg/day depending on hyperglycemia severity 1, 5
Fasting plasma glucose target: 80-130 mg/dL 5
Titration algorithm: Increase by 2 units every 3 days until FPG goal achieved without hypoglycemia 1, 5
Hypoglycemia management: Reduce dose by 10-20% if hypoglycemia occurs 5, 3
Metformin continuation: Mandatory unless contraindicated; reduces weight gain, insulin dose, and hypoglycemia 1, 2

Intensification When Basal Insulin Insufficient:

If fasting glucose is controlled but HbA1c remains above target, add a GLP-1 receptor agonist rather than prandial insulin when possible. 1

Preferred approach: Add GLP-1 RA for weight and hypoglycemia benefits 1
Alternative: Add prandial insulin with largest meal 5
- Start 4 units or 10% of basal dose 5
- Increase by 1-2 units or 10-15% every 3-7 days based on postprandial glucose 5
Full basal-bolus: 50% total daily dose as basal, 50% split among meals 5

Monitoring Requirements

Self-Monitoring of Blood Glucose (SMBG)

Blood glucose monitoring is integral to insulin therapy and must not be omitted from the care plan. 2

Basal insulin titration: Use fasting plasma glucose values 1, 2
Prandial insulin adjustment: Use both fasting and postprandial glucose (2 hours after largest meal) 5, 2
Frequency during titration: Check fasting daily, pre-meal before each meal, and 2-hour postprandial 5
Increased monitoring: Required during illness, travel, routine changes, or dose adjustments 5

Continuous Glucose Monitoring (CGM)

CGM is superior to blood glucose monitoring and improves outcomes with all insulin regimens. 1

Type 1 diabetes: Strongly recommended for all patients 1
Glycemic variability assessment: Best evaluated by CGM when prone to fluctuations 2
AID system requirement: Essential for automated insulin delivery function 1

HbA1c Monitoring

Frequency: Every 3 months until target achieved, then every 3-6 months 1, 5
Reassessment trigger: If not meeting goals, intensify therapy without delay 1

Specific Insulin Brands and Delivery Systems

Rapid-Acting Analogs

Humalog (lispro), NovoLog/NovoRapid (aspart), Apidra (glulisine) 8
Fiasp (faster aspart), Lyumjev (ultra-rapid lispro): Ultra-rapid formulations 1

Long-Acting Analogs

Lantus/Basaglar (glargine U-100): Once daily, may require twice-daily dosing in some patients 1
Toujeo (glargine U-300): More concentrated, longer duration 1
Levemir (detemir): Often requires twice-daily dosing 1
Tresiba (degludec): Ultra-long acting, most flexible timing 5, 3

Premixed Insulins

NovoLog Mix 70/30, Humalog Mix 75/25, Humulin 70/30 1

Delivery Devices

Vials and syringes: Least expensive, 0.5-1 unit increments 1
Insulin pens: Improved adherence, easier use, 0.5-1 unit increments 1
Connected insulin pens: Track doses, integrate with apps 1
Insulin pumps (CSII): Continuous subcutaneous infusion, use only rapid/ultra-rapid analogs 1
Automated insulin delivery systems: Hybrid closed-loop, algorithm-driven adjustments 1
Inhaled insulin (Afrezza): Rapid-acting alternative to injectable prandial insulin in U.S. 1

Special Populations and Situations

Renal Impairment

Lower insulin doses required as eGFR decreases; titrate based on clinical response with increased hypoglycemia vigilance. 1

Dose reduction: Necessary due to decreased insulin clearance 1
Hypoglycemia risk: Increases with severity of kidney impairment 1

Steroid-Induced Hyperglycemia

NPH insulin administered concomitantly with morning glucocorticoid dose is the standard approach. 3

Rationale: NPH peak (4-6 hours) matches steroid-induced daytime hyperglycemia 3
Monitoring: Check glucose every 4-6 hours after steroid administration 3
Tapering caution: Reduce insulin proportionally to avoid hypoglycemia 3

Hospital Settings

Critically ill: IV insulin infusion, target 140-180 mg/dL (7.8-10.0 mmol/L) 5
Non-critically ill: Premeal <140 mg/dL, random <180 mg/dL 5
Hypoglycemia threshold: Modify regimen if glucose <100 mg/dL, urgent adjustment if <70 mg/dL 5

Common Pitfalls and How to Avoid Them

Overbasalization

Clinical signals include basal dose >0.5 units/kg/day, high bedtime-morning glucose differential, hypoglycemia, and high glycemic variability. 1

Action: Add prandial insulin or GLP-1 RA rather than continuing to increase basal dose 1

Therapeutic Inertia

Reassess and modify regimen every 3-6 months; do not delay intensification when goals unmet. 1

Consequence: Prolonged hyperglycemia increases complication risk 1

Abrupt Discontinuation of Oral Agents

Do not stop oral medications abruptly when starting insulin due to rebound hyperglycemia risk. 2

Metformin: Continue indefinitely unless contraindicated 1, 2

Intramuscular Injection

Avoid IM delivery, especially with long-acting insulins, as severe hypoglycemia may result. 2

Prevention: Use 4-mm needles, proper injection technique 2

Injection into Lipohypertrophy

Never inject into lipohypertrophic areas as this distorts absorption and causes erratic glucose control. 2

Prevention: Systematic site rotation, regular site examination 1, 2

Follow-Up and Ongoing Management

Patient Education Requirements

Hypoglycemia recognition and treatment: 15-20g fast-acting carbohydrate for glucose <70 mg/dL, recheck in 15 minutes 5
Glucagon administration: Family members must be trained for severe hypoglycemia 5
Injection technique demonstration: Verify at each visit 7
Sick day management: Continue insulin even when unable to eat, increase monitoring frequency 5
Carbohydrate counting: Essential for prandial insulin dose calculation using insulin-to-carbohydrate ratios 1

Dose Adjustment Principles

Basal insulin: Adjust based on overnight, fasting, or daytime glucose outside prandial insulin activity 1
Prandial insulin: Adjust insulin-to-carbohydrate ratio if post-meal glucose consistently out of target 1
Correction insulin: Adjust insulin sensitivity factor if corrections don't bring glucose into range 1

Cost Considerations

Choice of basal insulin should be based on person-specific considerations, including cost. 1

Analog insulins: More expensive but lower hypoglycemia risk and better postprandial control 2
Human insulins (NPH, regular): Less expensive but higher hypoglycemia risk 1, 2
Device selection: Vials/syringes least expensive; pumps and AID systems most expensive 1

What are the different types of insulin therapy, including indications, monitoring, administration techniques, and brands?

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