PREDICTIVE FACTORS ASSOCIATED WITH PRIMARY FAILURE TO EXENATIDE AND NON GOAL ATTAINMENT IN PATIENTS WITH TYPE 2 DIABETES

Abstract

Objective: We prospectively analysed HbA_1c 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 HbA_1c 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 HbA_1c ≤ 7.5% (58 mmol/mol) at 12 months; non-goal-achievers (NGA, n = 16; HbA_1c > 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 HbA_1c 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 HbA_1c 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, HbA_1c 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 HbA_1c and absolute decrement in HbA_1c over the study period. Logistic regression demonstrated that baseline HbA_1c was the strongest predictor for target attainment following exenatide therapy (p < 0.001), with age to a lesser degree (p = 0.089).

Conclusion: Baseline HbA_1c is a major predictor of response to exenatide treatment, defined as target HbA_1c (≤ 7.5%, 58 mmol/mol) attainment. The lower the baseline HbA_1c, the greater the likelihood of reaching the target HbA_1c at 12 months, even though patients with higher baseline HbA_1c benefited from the largest absolute reduction in HbA_1c levels.

Keywords:

• exenatide
• target attainment
• type 2 diabetes
• glycaemic control.