In an adult (≥18 years) with a well‑defined keloid and no uncontrolled diabetes, what is the recommended intralesional regular human insulin regimen for keloid flattening?

Intralesional Insulin for Keloids

Intralesional insulin is not currently recommended as a standard treatment for keloids, despite emerging evidence showing promise. The provided evidence contains no guidelines or FDA-approved protocols for intralesional insulin use in keloid management, and the available research is insufficient to establish a definitive regimen.

Current Evidence Status

The evidence base for intralesional insulin in keloids consists of limited research studies without established clinical guidelines or regulatory approval for this indication 1. The FDA labeling for insulin products describes only their approved use for glucose metabolism regulation in diabetes, with no mention of dermatologic or intralesional applications 1.

Research Findings on Insulin

One recent study (2025) compared intralesional insulin to botulinum toxin-A and corticosteroids in 63 keloid patients over 4 monthly sessions 2. The insulin group showed:

• 66.6% volume reduction (compared to 75% for corticosteroids and 25.3% for BTX-A)
• Superior improvement in pigmentation, thickness reduction, and symptom relief compared to BTX-A
• Statistical inferiority to corticosteroids but better performance than BTX-A alone

However, this single study provides no specific dosing protocol, concentration, or injection technique for insulin administration in keloids 2.

A 2026 network meta-analysis examining 51 studies with 23 interventions found that insulin data were too limited to rank meaningfully against established therapies 3. The analysis concluded that "novel agents (insulin and BTX-A) suggest potential, but further research with standardized methodologies is crucial" 3.

Evidence-Based Recommendations

Given the absence of guidelines and limited research, intralesional insulin cannot be recommended as a primary or standard treatment for keloids. The evidence hierarchy strongly supports established therapies:

First-Line Treatment

• Intralesional triamcinolone acetonide (TAC) combined with 5-fluorouracil (5-FU) represents the most evidence-based approach 3, 4, 5
• This combination showed the most favorable balance between efficacy and recurrence reduction across multiple meta-analyses 5
• SUCRA ranking: 5-FU + corticoids scored 0.78 for effectiveness 3

Treatment Algorithm for Keloids

For established keloids:

1. Start with intralesional TAC + 5-FU as pharmacological backbone 4, 5
2. Add adjuncts based on dominant features:
   • Cryotherapy for relatively thin lesions 4
   • Fractional CO₂ laser for thickness and texture 4
   • Botulinum toxin A when tension, pruritus, or contracture is prominent 4

For enhanced efficacy:

• Consider triple therapy: 5-FU + corticoids + YAG laser (SUCRA 0.95, highest probability of effectiveness) 3

Critical Gaps and Pitfalls

Major limitations preventing insulin recommendation:

• No standardized concentration, volume, or dosing interval established
• No injection technique protocols specific to keloid treatment
• Single comparative study with small sample size (n=21 per group) 2
• No long-term recurrence data
• No safety profile established for intralesional dermatologic use
• FDA labeling addresses only subcutaneous/intravenous administration for diabetes 1

Common pitfall: Attempting to extrapolate diabetic insulin dosing (0.15 units/kg subcutaneously) 1 to intralesional keloid treatment is inappropriate and potentially dangerous, as tissue responses, pharmacokinetics, and safety profiles differ fundamentally between these applications.

Safety Considerations

The insulin FDA label describes risks of hypoglycemia, injection site reactions, and lipodystrophy with approved subcutaneous use 1. Intralesional administration in non-diabetic patients carries unknown risks including:

• Systemic hypoglycemia (particularly concerning in non-diabetic patients)
• Local tissue reactions
• Unpredictable absorption from scar tissue

Until rigorous clinical trials establish safety and efficacy parameters, intralesional insulin should be considered investigational only 2, 3.