Limitations of the HOMA-B Score for Assessment of β -Cell Functionality in Interventional Trials—Results from the PIOglim study

Abstract

Background:

Drugs with unspecific stimulating effects on β-cell secretion increase the homeostasis model assessment (HOMA)-B score, indicating improved β-cell “function.” We investigated whether the β-cell protection provided by adding pioglitazone (PIO) to glimepiride (GLIM) in comparison to up-titrating the GLIM dose alone is reflected by appropriate changes in several measures of β-cell function, including HOMA-B score.

Methods:

This double-blind, parallel prospective 6-month study was performed with 82 patients (47 men, 35 women; age, 61 ± 9 years; duration of disease, 5.3 ± 4.4 years; body mass index, 32.6 ± 6.0 kg/m²; hemoglobin A1c [HbA1c], 7.3 ± 0.7%) with GLIM monotherapy (1–3 mg). They were randomized to receive a GLIM + PIO combination with up-titration (2 mg + 30 mg/4 mg + 30 mg/4 mg + 4 mg) or to remain on GLIM (up-titration 4/5/6mg). Observation parameters determined at baseline and end point included HOMA-B, HOMA-IR, HbA1c, glucose, insulin, and intact proinsulin.

Results:

There was a slight increase in the HOMA-B score in the GLIM group but not in the GLIM + PIO arm (baseline/end point: for GLIM, 71 ± 48/88 ± 64; for PIO + GLIM, 74 ± 56/69 ± 52). Improvements in the other observation parameters were predominantly detected in the PIO + GLIM group (HbA1c, 7.20 ± 0.61%/6.36 ± 0.90%; HOMA-IR, 7.0 ± 4.5/4.1 ± 2.1; intact proinsulin, 12.4 ± 10.3/7.6 ± 4.8 pmol/L [all P < 0.05 vs. baseline]) compared with the GLIM group (HbA1c, 7.45 ± 0.69%/7.15 ± 0.97% [P < 0.05]; HOMA-IR, 7.4 ± 4.5/7.5 ± 4.3 [not significant]; intact proinsulin, 17.3 ± 21.6/16.3 ± 15.5 pmol/L [not significant]).

Conclusions:

The PIO + GLIM combination led to overall improvement of laboratory biomarkers for β-cell function, except for HOMA-B. Glimepiride up-titration had no such effects but increased the HOMA-B score. HOMA-B seems to provide misleading results when used as a diagnostic tool in patients treated with sulfonylurea drugs. A corrective term for consideration of proinsulin in the HOMA-B equation may address this limitation.