Treatment of patients with type 2 diabetes with exenatide once weekly versus oral glucose-lowering medications or insulin glargine: achievement of glycemic and cardiovascular goals

Abstract

Background: Diabetes is associated with a higher risk for adverse cardiovascular outcomes. To improve the health outcomes of patients with type 2 diabetes (T2DM), the American Diabetes Association (ADA) recommended target goals for the improvement of glycemic control and the reduction of cardiovascular risk factors associated with the disease. This retrospective analysis calculated the absolute benefit increase (ABI) of using exenatide once weekly (QW), a glucagon-like peptide-1 (GLP-1) receptor agonist, vs an oral glucose-lowering medication or insulin glargine to achieve ADA-recommended goals. The number needed to treat (NNT) to achieve these goals was also calculated and provides a useful clinical metric for comparing potential therapies from different drug classes.

Methods: Patient data from three double-blind or open label, 26-week, randomized, controlled trials were retrospectively analyzed separately. ABI and NNT were calculated by comparing the percentage of patients treated with exenatide QW (N = 641) vs metformin (N = 246), sitagliptin (N = 329), pioglitazone (N = 328), or insulin glargine (N = 223), who achieved a single glycemic, weight, blood pressure, or lipid goal or a composite of these recommended goals, during the DURATION-2, -3, and -4 clinical trials.

Results: Significant ABIs favoring exenatide QW over all four glucose-lowering medications were observed for at least one HbA1c glycemic goal. NNTs of 4 and 5 were calculated when exenatide QW was compared to sitagliptin for attaining HbA1c goals of <7.0% and ≤6.5%, respectively. Additionally, significantly more patients using exenatide QW compared to sitagliptin, pioglitazone, or insulin glargine attained the composite goal of HbA1c <7% or ≤6.5%, without weight gain or hypoglycemia. Exenatide QW was also favored over sitagliptin and insulin glargine for the achievement of the composite goals of HbA1c <7% (or ≤6.5%), systolic blood pressure <130 mm Hg, and low-density lipoprotein <2.59 mmol/L. For most goals, exenatide QW and metformin had similar effects in treatment naïve patients.

Conclusions: This analysis assessed the between-therapy differences in achieving therapeutic goals with therapies commonly used for glycemic control in patients with T2DM. In clinical trials, exenatide QW assisted more patients in reaching the majority of ADA-recommended therapeutic goals than treatment with sitagliptin, pioglitazone, or insulin glargine.

Trial registration: NCT00637273, NCT00641056, NCT00676338.

Figures

Figure 1

Absolute Benefit Increase (ABI) of Exenatide QW (ExQW) vs Metformin. Forest plot depicts the ABI (%) ± 95% CI of ExQW vs metformin. ABI = 0% indicates no benefit; ABI <0% indicates metformin provides a benefit vs ExQW.

Figure 2

Absolute Benefit Increase (ABI) of Exenatide QW (ExQW) vs Sitagliptin. Forest plot depicts the ABI (%) ± 95% CI of ExQW vs sitagliptin. Data comparing ExQW to sitagliptin originate from DURATION-2 (filled circles) and DURATION-4 (open circles) studies. ABI = 0% indicates no benefit; ABI <0% indicates sitagliptin provides a benefit vs ExQW.

Figure 3

Absolute Benefit Increase (ABI) of Exenatide QW (ExQW) vs Pioglitazone. Forest plot depicts the ABI (%) ± 95% CI of ExQW vs pioglitazone. Data comparing ExQW to pioglitazone originate from DURATION-2 (filled circles) and DURATION-4 (open circles) studies. ABI = 0% indicates no benefit; ABI <0% indicates pioglitazone provides a benefit vs ExQW.

Figure 4

Absolute Benefit Increase (ABI) of Exenatide QW (ExQW) vs Insulin Glargine. Forest plot depicts the ABI (%) ± 95% CI of ExQW vs insulin glargine. ABI = 0% indicates no benefit; ABI <0% indicates insulin glargine provides a benefit vs ExQW.