HOMA-IR Ranges and Clinical Interpretation
Values above 2.5 consistently indicate pathological insulin resistance, with a normal upper limit of approximately 2.86 based on the most recent population reference intervals. 1
Normal and Pathological Thresholds
Established Reference Ranges
- Normal insulin sensitivity: HOMA-IR 0.39–2.86 (95% reference interval from a large Brazilian population study of over 21,000 individuals) 2
- Pathological insulin resistance: HOMA-IR >2.5 (European guideline consensus threshold) 1
- Optimal metabolic health: HOMA-IR <2.0 generally associated with better clinical outcomes 1
Clinical Risk Stratification
While no universal severity grading system exists, the following framework emerges from guideline recommendations and population studies:
- Normal/optimal: <2.0 1
- Mild insulin resistance: 2.0–2.5 1, 2
- Significant insulin resistance: 2.5–5.0 1, 3
- Severe insulin resistance: >5.0 4
Important Caveats for Interpretation
Population-Specific Considerations
Cut-off values vary by BMI category, with higher thresholds appropriate for individuals with obesity. 3 In the ELSA-Brasil cohort, the optimal HOMA-IR cut-off for metabolic syndrome was 2.35 overall, but increased progressively in overweight and obese categories. 3
Computational Method Matters
The calculation method significantly affects both the numeric value and clinical interpretation. 5
- HOMA1 formula (original): [fasting glucose (mmol/L) × fasting insulin (mU/mL)] ÷ 22.5 1
- Insulin resistance threshold: ≥2.5 5
- HOMA2 calculator (computer model): More complex algorithm
- Insulin resistance threshold: ≥1.4 5
The HOMA1 formula shows stronger associations with metabolic syndrome (OR 2.04 vs 1.43) and better diagnostic accuracy (AUC 0.741 vs 0.680) compared to HOMA2. 5
Clinical Validity Depends on Diabetes Status
HOMA-IR is most valid in non-diabetic individuals where pancreatic β-cells can still adapt to insulin resistance. 1, 6 Its validity is questionable in established type 2 diabetes because the model depends on preserved β-cell function. 1, 7
When to Use HOMA-IR Clinically
Recommended Applications
- Metabolic dysfunction-associated steatotic liver disease (MASLD) evaluation in adults without established type 2 diabetes 1, 6
- Polycystic ovary syndrome (PCOS) assessment as a metabolic outcome measure (average HOMA-IR in PCOS: 2.68) 1, 6
- Clinical trials requiring insulin resistance as an endpoint 1
- Cardiovascular risk stratification when metabolic syndrome components are present 1
When NOT to Use HOMA-IR
Routine screening is not recommended by the American Diabetes Association (Grade B evidence), as insulin assays are considered primarily useful for research purposes. 1 Clinical assessment using BMI and acanthosis nigricans is preferred over laboratory testing for insulin resistance screening. 1
Alternative Assessment When HOMA-IR Unavailable
Fasting Insulin Alone
When HOMA-IR cannot be calculated, fasting insulin provides reasonable clinical assessment: 1
- Normal: <15 mU/L
- Borderline high: 15–20 mU/L
- High (insulin resistance): >20 mU/L
Clinical Assessment Priority
Metabolic syndrome criteria should guide management decisions rather than HOMA-IR alone. 1 The presence of metabolic syndrome warrants evaluation regardless of HOMA-IR value. 1
Key Pitfalls to Avoid
- Insulin assay variability: Different laboratories use different insulin assays with wide variation; proper reference values must be established for your specific laboratory 1, 5
- Using HOMA-IR in established diabetes: The model loses validity when β-cell function is significantly impaired 1, 6, 7
- Ignoring BMI context: A HOMA-IR of 2.5 may be normal in obesity but pathological in normal-weight individuals 3
- Mixing computational methods: HOMA1 and HOMA2 produce different numeric values and require different thresholds 5