Extended-release exenatide may reduce CV event risk
MedWire News: A once-weekly formulation of the glucagon-like peptide, exenatide, may decrease cardiovascular (CV) event risk in patients with Type 2 diabetes through combined effects on various risk factors, modeling of NHANES data suggests.
Exenatide is currently approved for use in the USA in Type 2 diabetes patients, and the twice-daily formulation has been shown to reduce hyperglycemia and body weight by enhancing glucose-dependent insulin secretion, suppression of elevated glucagon levels, slowing gastric emptying, and increasing satiety.
A long-acting formulation of exenatide allows once-weekly dosing, and trials have shown its association with superior reductions in glycated hemoglobin (HbA1c) compared with twice-daily exenatide. However, the effects of the long-acting formulation on long-term CV outcomes are not yet known.
Julia Gaebler (Amylin Pharmaceuticals, San Diego, California, USA) and co-workers constructed a mathematical model to estimate the effect of long-acting exenatide on cardiovascular outcomes. The model used data from the US National Health and Nutrition Examination Survey (NHANES), from a representative sample of patients with Type 2 diabetes aged 18-80 years who had received no prior treatment for their diabetes, or had received oral agents only.
As reported in the journal Diabetes, Obesity and Metabolism, the relative reduction in risk for major adverse CV events was two-to-three fold greater after once-weekly exenatide treatment than with intensive glycemic control using conventional antidiabetic treatments, in comparison with standard care. This difference was observed despite the fact that both treatments reduced HbA1c levels by approximately the same amount.
The long-acting formulation had a similar positive effect on rates of neuropathy as intensive glycemic control with conventional agents, over a simulated period representing 20 years of treatment. It had a significantly greater positive effect on renal complications over the same time-frame, however.
The authors conclude that the results of their analysis "are limited by the assumptions used to model the effects of extended-release exenatide over time."
Nevertheless, "accumulated real-world effectiveness data from the use of exenatide twice daily in over 1 million patient-years of exposure suggest that the magnitude of change in global CV disease risk is theoretically sufficient to have a clinically important impact on macrovascular outcomes consistent with the findings of this simulation" they add.
"Our simulation suggests that these benefits may translate into clinically meaningful reductions in CV events."
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By Philip Ford