Six-month exenatide improves HOMA hyperbolic product in type 2 diabetic patients mostly by enhancing beta-cell function rather than insulin sensitivity.
OBJECTIVE
This study aimed to determine whether or not the improvement of glycaemic control with 6-month exenatide therapy in type 2 diabetic patients with secondary failure to combined oral therapy is related to amelioration of β-cell function and/or insulin sensitivity and their combined product.


METHODS
Thirty-three patients with type 2 diabetes were investigated. Their β-cell function and insulin sensitivity were measured using Homoeostasis Model Assessment [HOMA-B, HOMA-S and HOMA hyperbolic product (BxS)]. Additional endpoints included changes in weight, HbA(1c) and plasma adiponectin, as well as baseline clinical and biological characteristics, as potential predictors of HbA(1c) response.


RESULTS
After 6 months, unadjusted HOMA-B increased from 33 ± 24% to 43 ± 23% (P=0.0210), whereas there was no significant change in HOMA-S (from 58 ± 35% to 61 ± 40%). The hyperbolic product increased by a relative 70% (from 15 ± 7% to 22 ± 15%; P=0.0055). Body mass index decreased from 32.2 ± 5.1 kg/m(2) to 31.0 ± 4.8 kg/m(2) (P<0.0001) and HbA(1c) from 8.8 ± 1.0% to 7.6 ± 1.2% (P<0.0001). No change was observed in adiponectin concentrations. Higher baseline HbA(1c) values were a significant predictor of therapeutic response.


CONCLUSIONS
Exenatide significantly increased HOMA-B and hyperbolic product over a 6-month treatment period with no overall change in insulin sensitivity, despite weight loss. Thus, improved β-cell function rather than increased insulin sensitivity accounts for the bulk of HbA(1c) reduction following 6 months of exenatide treatment.
Preumont
V
V
Service of Endocrinology and Diabetology, St-Luc Academic Hospital, Université catholique de Louvain, Avenue Hippocrate 10, UCL 54.74, 1200 Brussels, Belgium. vanessa.preumont@uclouvain.be
Hermans
M-P
MP
Brichard
S
S
Buysschaert
M
M
D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism; D004334:Drug Administration Schedule; D000077270:Exenatide; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D007328:Insulin / Q000378:metabolism*; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D011237:Predictive Value of Tests; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D014688:Venoms / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*
D015415:Biomarkers; D001786:Blood Glucose; D000077270:Exenatide; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D010455:Peptides; D014688:Venoms