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Does Byetta Work for Type 1’s?

GLP-1 agonist may prove beneficial to type 1 diabetes….

Kevan Herold, MD, of Yale University, and colleagues reported that the GLP-1 agonist exenatide (Byetta) may have metabolic effects on patients with type 1 diabetes.

In a small trial that consisted of 17 patients with type 1 diabetes, exenatide was given before a mixed meal tolerance test and demonstrated a significant reduction in glucose excursions (p<0.001). Gastric emptying was also delayed (p=0.0017) even though insulin secretion rates didn’t increase.

Interestingly, exenatide had no metabolic effects when given before an intravenous glucose tolerance test.

"The metabolic effects require oral absorption of nutrients, since we found no glycemic or hormonal effects of exenatide on the responses to intravenous glucose," they wrote.

Other studies on GLP-1 drugs have shown potential benefits for those with type 1 disease, especially for those that still had residual beta cell function. However, the data was overwhelmed by the controversy over GLP-1 drugs potentially having adverse effects on the pancreas.

Herold and colleagues set out to investigate the data by enrolling 17 participants with the condition. About half of them were noted as still having residual insulin production.

All participants received two mixed meal tolerance tests and two intravenous glucose tolerance tests, with and without pre-treatment with exenatide. Outcomes measured included glucose excursions, insulin secretion rates, glucagon, endogenous GLP-1, and gastric inhibitory polypeptide (GIP) levels after each scenario.

The research team noted that they did not measure raw C-peptide levels, but instead calculated insulin secretion rates. Their reasoningn was because insulin secretion rates give a more accurate assessment of beta cell function.

Overall, glucose excursions were reduced by 33% with exenatide for all participants during the meal test portion of the study. This included those with and those without residual insulin function (p<0.001).

Among the other outcomes, gastric emptying, as quantified via acetaminophen absorption, was also delated for all patients (p<0.0017), and glucagon was substantially suppressed (p=0.0015).

The glucagon to glucose ratio was considerably increased with exenatide, which implies that the drop in glucose excursions "involves factors in addition to the effects of glucagon itself," noted Herold and his colleagues.

Exenatide did not show to have changed the absolute insulin secretion rates for any patients, although the ratio of insulin secretion rates to glucose levels was increased specifically in patients with preserved beta cell function (p=0.0078).

The researchers concluded that this probably reflects reduced glucose levels in patients who were "already maximally secreting insulin."

During the intravenous glucose tolerance test portion of the study, none of these effects were seen. Exenatide displayed no effect on glucose responses, gastric emptying, insulin secretory response, or on the relationship between insulin secretion and glucose levels.

The group noted that the stimuli of a mixed meal and intravenous glucose are very different, so the metabolic effects of exenatide that were seen likely require oral absorption of nutrients.

"The most significant metabolic consequence of exenatide administration appears to involve the delay in absorption of nutrients and a reduced rise in glucose as a consequence," they wrote.

The trial, while small, suggests that GLP-1 agonists may be a useful tool in type 1 diabetes just like it is in type 2 disease. However, further research and more trials with a larger number of participants are still needed.

Practice Pearls:
  • The effect was not present after IV infusion of glucose, suggesting a mechanism that is dependent upon oral ingestion.
  • This within-patient study demonstrated that exenatide may improve serum glucose profiles when given before a meal.

Ghazi T, et al "Acute metabolic effects of exenatide in patients with type 1 diabetes with and without residual insulin to oral and IV glucose challenges" Diabetes Care 2013; DOI: 10.2337/dc13-1169.