GLP-1 RA Efficacy with BMI

A patient’s baseline body mass index (BMI) did not seem to have an effect on the efficacy of the glucagon-like peptide (GLP)-1 receptor agonist exenatide twice daily added to insulin glargine among a group of patients with type 2 diabetes, according to the results of a post hoc analysis published in Diabetes, Obesity and Metabolism.

“In this secondary analysis of two clinical trials in which patients with type 2 diabetes were randomized to add-on exenatide twice daily versus add-on insulin lispro or placebo, while taking background insulin glargine with or without metformin and/or pioglitazone, baseline BMI was not correlated with changes from baseline in the efficacy parameters evaluated,” wrote Bruce H.R. Wolffenbuttel, MD, PhD, of University of Groningen, the Netherlands, and colleagues. “In both studies, exenatide twice daily was associated with significant reductions in HbA1c and body weight.”

According to the background of the study, certain countries restrict reimbursement for the use of GLP-1 receptor agonists to only those patients with a BMI of 35 kg/m² or greater. Therefore, in this study, Wolffenbuttel and colleagues wanted to evaluate the validity of that restriction by examining the relationship between BMI and the effects of exenatide twice daily.

In this study, the researchers conducted a post hoc analysis of two randomized, non-inferiority studies. In the first study, exenatide was compared with insulin lispro added to background insulin glargine and metformin (n=627). In the second study, exenatide was compared with placebo added to insulin glargine with or without metformin and/or pioglitazone (n=259). The researchers assessed the relationship between BMI ranges (<30, 30-35, and >35 kg/m²) and treatment effects of exenatide twice daily.

All patients across all BMI ranges experienced significant reductions in HbA1c. The patients assigned to exenatide in both studies had numerically greater reductions in fasting plasma glucose than those who were assigned the comparators across all BMI groups except those with a BMI less than 30 assigned placebo.

In addition, a greater number of patients achieved an HbA1c of less than 7% when assigned exenatide versus the comparators in all of the BMI groups except for those with a BMI of 30-35 in the lispro-comparator study. An HbA1c less than 7% plus no weight gain was higher among patients assigned exenatide twice daily versus insulin-lispro and placebo.

Based on these results, the researchers wrote that “the decision by some European national authorities or health insurance companies to restrict GLP-1RA reimbursement to patients with BMI >35 kg/m² is not consistent with medical evidence.”

The analysis also showed that all patients assigned to exenatide had significant reductions in body weight except those with a BMI less than 30 in the placebo study (P<0.05). In contrast, patients assigned to the comparators had increases in body weight.

Finally, there were significant decreases in systolic blood pressure across all of the BMI groups when assigned exenatide compared with insulin lispro (P<0.0001).

“There is evidence of clinically meaningful glycaemic and weight benefits from the addition of exenatide twice daily to insulin glargine in both patients of normal weight and patients with mild to severe obesity, and there does not appear to be a threshold below which exenatide twice daily is not effective,” the researchers wrote. “Limiting reimbursement to patients with obesity (BMI >35 kg/m²) may result in the undertreatment of patients with lower BMI and may increase their risk of hypoglycaemia and unwanted weight gain.”

The studies included in the analysis were supported by the Alliance of Eli Lilly and Company and Amylin Pharmaceuticals and the alliance of Bristol-Myers Squibb and AstraZeneca.

Reference: Wolffenbuttel BH, et al. Relationship of body mass index with efficacy of exenatide twice daily added to insulin glargine in patients with type 2 diabetes. Diabetes Obes Metab. Epub 2016 Mar 29.