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Exenatide enhances in-hospital glycemic control

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February 11, 2019

For general medicine and surgery patients, glycemic control can be improved with the use of the short-acting GLP-1 receptor agonist exenatide both with and without basal insulin, according to findings published in Diabetes Care.

Guillermo E. Umpierrez

“Based on their mechanism of action and safety profiles, there has been a great interest in using incretin-based therapies instead of, or complementary to, an insulin-based approach to improve glycemic control in hospitalized patients with diabetes,” Guillermo E. Umpierrez, MD, professor of medicine in the division of endocrinology and metabolism at Emory University School of Medicine and the chief of diabetes and endocrinology at Grady Memorial Hospital in Atlanta, and colleagues wrote. “Use of these agents is attractive in hospitalized patients owing to their metabolic effects, such as glucose-dependent stimulation of insulin secretion and inhibition of glucagon secretion, which leads to improved glycemic control with low rates of hypoglycemia.”

Umpierrez and colleagues conducted a multicenter, prospective, open-label, randomized trial with 150 adults who were hospitalized with noncritically ill conditions at Emory University Hospital, Grady Memorial Hospital in Atlanta, Temple University Hospital in Philadelphia or Vanderbilt University Medical Center in Nashville, Tennessee. Each participant had been diagnosed with type 2 diabetes previously and treated with diet, oral agents or low-dose insulin.

Participants were randomly assigned to in-hospital treatment with exenatide (Byetta, AstraZeneca; n = 47; mean age, 55 years; 49% women; mean blood glucose at admission, 220.7 mg/dL), exenatide with basal insulin (n = 51; mean age, 55 years; 49% women; mean blood glucose at admission, 186.9 mg/dL) or a basal-bolus regimen (n = 52; mean age, 57 years; 50% women; mean blood glucose at admission, 195.1 mg/dL). The researchers assessed mean daily blood glucose concentrations as the primary outcome, but also reported hypoglycemic events, significant hypoglycemia, severe hypoglycemia and hyperglycemic events.

Participants who received exenatide in addition to basal insulin had lower mean blood glucose compared with exenatide therapy by itself (P = .02). The highest proportion of participants to fall within the target range for blood glucose of 70 mg/dL to 180 mg/dL was found in the exenatide plus basal insulin group (77.7%). The basal-bolus (63.3%; P = .005) and exenatide alone (62.3%; P = .07) groups had similar proportions of participants to fall within the range. In addition, participants with exenatide alone (0%) and exenatide plus basal insulin (6%) had less reported hypoglycemia compared with the basal-bolus regimen (12%), but the researchers noted that this did not reach statistical significance.

In terms of efficacy, gastrointestinal adverse effects were low in the entire cohort, and no statistically significant difference was found among the three groups, although there were more reports in both the exenatide alone and exenatide plus basal insulin groups. There was also no major difference between mean length of stay in the hospital for the three groups.

“Our results indicate that exenatide is well-tolerated and can be used safely in non-ICU hospital settings,” the researchers wrote. – by Phil Neuffer

Disclosures: This study was supported by AstraZeneca. Umpierrez reports that he has received unrestricted research support for inpatient studies from AstraZeneca, Merck, Novo Nordisk and Sanofi. Please see the study for all other authors’ relevant financial disclosures.

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Basal-bolus insulin is currently recommended for the majority of non-critically ill hospitalized patients. An advantage of basal-bolus insulin in the hospital is that it allows rapid titration in patients whose clinical course can evolve over a matter of hours to days. Drawbacks include increased risk for hypoglycemia and the need for multiple daily injections. GLP-1 receptor agonists, by virtue of their glucose-dependent insulin stimulation, do not share this risk for hypoglycemia and are an attractive option for use in hospitalized patients; however, until this study, these agents had not been studied in this population.

In the first randomized controlled trial using a GLP-1 receptor agonist for glycemic control in non-critically ill hospitalized patients, Fayfman and colleagues sought to determine whether twice-daily exenatide is a safe and effective alternative to basal-bolus insulin in general medical and surgical ward patients. Although no patients treated with exenatide alone experienced hypoglycemia, it was surprising that rates of hypoglycemia were not statistically different between the exenatide-plus-basal and basal-bolus insulin groups. I wonder whether failure to detect differences in the rate of hypoglycemia was a limitation of the sample size of the study, as there did appear to be a higher proportion of blood glucose of less than 70 mg/dL in the basal-bolus compared with exenatide-plus-basal insulin group (12% vs. 6%). Despite the fact that exenatide is a twice-daily injection and bolus insulin is given three times daily before meals, the total number of injections per day was not found to be lower in the exenatide-plus-basal insulin group (who also received correctional insulin doses as needed).

As expected, rates of gastrointestinal side effects were higher in both arms receiving exenatide. The study had careful selection criteria, which excluded patients with a history of pancreatitis, gastrointestinal obstruction and those requiring gastrointestinal suction or with active nausea or vomiting, parenteral nutrition or alcoholism. Considering that such symptoms or conditions are not uncommonly encountered in hospitalized patients, adopting the use GLP-1 receptor agonists in hospitalized patients would require clear patient selection criteria.

Although limited by the relatively small number of patients in each treatment group and the open-label design, this study suggests that a basal insulin/GLP-1 receptor agonist combination is as at least as effective as basal-bolus insulin for hospitalized patients. Considering the challenge of timing nutritional insulin with meal intake in hospitalized patients, these findings are promising in that the use of GLP-1 receptor agonists in the hospital would offer flexibility in providing “prandial coverage” without any deterioration in glycemic control. Further studies evaluating once daily GLP-1 receptor agonists or mixed combinations in hospitalized patients might be able to demonstrate the need for fewer daily injections, which would make a compelling argument for their use from a patient satisfaction standpoint.

Nestoras Mathioudakis, MD, MHS

Assistant Professor of Medicine,
Clinical Director, Division of Endocrinology, Diabetes and Metabolism
Johns Hopkins University School of Medicine

Disclosure: Mathioudakis reports no relevant financial disclosures.