Predictive factors associated with primary failure to exenatide and non goal attainment in patients with type 2 diabetes.

OBJECTIVE: We prospectively analysed HbA1c changes after 12 months of exenatide therapy and determined which baseline clinical and/or biological factors predict response. RESEARCH DESIGN AND METHODS: Open-label cohort of 41 subjects with type 2 diabetes (56% male) poorly-controlled on maximally-tolerated oral dual therapy. Age (mean ± 1SD) was 60 ± 10 years, and known diabetes duration 11 ± 8 years (mean ± 1SD). Biometric changes in weight, body mass index (BMI), waist circumference (WC), HOMA modeling (Homeostasis Model Assessment) of β-cell function (HOMA-B) and insulin sensitivity (HOMA-S) as well as in HbA1c were assessed at baseline, and after 6 or 12 months exenatide therapy. Patients were divided into three groups: goal-achievers (GA, n = 15), defined as achieving HbA1c ≤ 7.5% (58 mmol/mol) at 12 months; nongoal- achievers (NGA, n = 16; HbA1c > 7.5% (58 mmol/mol) at 12 months); and primary failure to exenatide therapy (early lack of efficacy; PF, n = 9). Non-responders represented the combined NGA plus PF patients.
RESULTS: The addition of exenatide to maximally-tolerated oral dual therapy led to target HbA1c attainment (≤ 7.5% (58 mmol/mol) at 1 year) in 37% of cases, associated with reduction in weight, BMI and waist circumference. GA were older than non-responders (64 ± 9 vs. 57 ± 10 years, p = 0.032). Diabetes duration was comparable. Baseline HbA1c was significantly lower in GA (8.3 ± 0.9 vs. 9.5 ± 0.9% in non-responders; p < 0.001). Baseline HOMA-B and HOMA-S were comparable, while HOMA product (BxS) was higher in GA (17 ± 6 vs. 14 ± 6% in non- responders, p = 0.04). At 12 months, HbA1c reached 7.0 ± 0.6% in GA vs. 9.0 ± 1.3% in non-responders. Weight, BMI and waist circumference decreased in both groups. In GA and non-responders, there was a marked relationship between baseline HbA1c and absolute decrement in HbA1c over the study period. Logistic regression demonstrated that baseline HbA1c was the strongest predictor for target attainment following exenatide therapy (p < 0.001), with age to a lesser degree (p = 0.089).
CONCLUSION: Baseline HbA1c is a major predictor of response to exenatide treatment, defined as target HbA1c (≤ 7.5%, 58 mmol/mol) attainment. The lower the baseline HbA1c, the greater the likelihood of reaching the target HbA1c at 12 months, even though patients with higher baseline HbA1c benefited from the largest absolute reduction in HbA1c levels.