GLP-1 receptor agonist may benefit high-risk diabetes

By Eleanor McDermid

Research shows that using a glucagon-like peptide-1 receptor agonist (GLP-1RA) instead of a rapid-acting insulin analogue at mealtimes can reduce glycaemic variability in high-risk patients with Type 2 diabetes.

"Improvement of several measures that are associated with medical risks supports further study of underlying physiologic mechanisms as well as the potential for this regimen to improve medical outcomes in a large and challenging population of patients", say Jeffrey Probstfield (University of Washington, Seattle, USA) and fellow FLAT-SUGAR Trial Investigators.

They say that the findings pave the way for studying how addressing glucose variability affects hard cardiovascular outcomes. With this in mind, they recruited patients similar to those in the ACCORD trial, in which a basal-bolus insulin regimen was associated with reduced myocardial infarction but increased cardiovascular and all-cause mortality.

The 102 patients were aged between 40 and 75 years and had either a previous cardiovascular event or at least two cardiovascular risk factors, in addition to being diabetic. After a run-in period of using metformin plus twice-daily basal insulin, with rapid-acting insulin at mealtimes, the patients were randomly assigned to either continue using rapid-acting insulin or switch to exenatide at a maximum daily dose of 20 µg.

After 26 weeks of treatment, glycated haemoglobin levels were similar between the groups, the researchers report in Diabetes Care.

However, the glucose coefficients of variation, measured by continuous glucose monitoring, fell by an average of 2.4 in the exenatide group, but increased by an average of 0.4 in the rapid-acting insulin group, giving a significant difference that favoured the exenatide group.

Levels of alanine aminotransferase fell by 10.7 units/L in the exenatide group, compared with a 0.9 unit/L rise in the rapid-acting insulin group, and the inflammatory marker serum amyloid A increased less in the former than the latter group.

These findings are "consistent with a metabolically favorable effect on the liver", say the researchers.

Along with a significant 4.8 kg reduction in weight in the exenatide group, versus a 0.7 kg increase in the insulin group, this suggests that longer treatment with the basal insulin-GLP-1RA regimen "might lead to medical benefits", they say.

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