There is ongoing debate among endocrinologists about the best strategy for treatment of type 2 diabetes (T2D) in the inpatient setting. Both hyperglycemia and hypoglycemia are associated with higher rates of hospital complications, longer length of stay and higher mortality. Oral medications are typically avoided in hospitalized patients due to disease-specific contraindications and food intake variability. Thus, clinical guidelines currently recommend the use of basal-bolus insulin as the preferred regimen for inpatient glycemic control.
Incretin-based therapies such as glucagon-like peptide 1 (GLP-1) exenatide represent an alternative, or complement to, an insulin-based approach. These agents have gained popularity in the outpatient setting because—in addition to their safety profiles and glucose-lowering effects—they promote weight loss. They are attractive for inpatient use due to their glucose-dependent stimulation of insulin secretion and inhibition of glucagon secretion, leading to low rates of hypoglycemia.
Putting Exenatide to the Test
A new study published in Diabetes Care tested the efficacy and safety of exenatide to control blood sugar in hospital patients with T2D. The multicenter, open-label, randomized trial tested exenatide alone and in combination with basal insulin in non-critically ill patients.
“GLP-1 agonists have never been studied with inpatient populations… we wanted to see if exenatide would be safe for use in this setting.”
“GLP-1 agonists are very effective in lowering blood sugar, but their mechanism of action is very different than insulin,” said coauthor Dara Mize, M.D., assistant professor in the Division of Diabetes, Endocrinology, & Metabolism at Vanderbilt University Medical Center. “They only release insulin when you need it; therefore, the risk of hypoglycemia is much lower. GLP-1 agonists have never been studied with inpatient populations and we wanted to see if exenatide would be safe for use in this setting.”
Comparing Exenatide Three Ways
A total of 150 general medicine or surgical patients in three institutions were randomized to exenatide alone (5 mg twice daily), exenatide plus basal insulin, or a basal-bolus insulin regimen. The primary endpoint was difference in blood glucose (BG) concentration among the three groups.
Patients were excluded from the study if they had a history of type 1 diabetes, diabetic ketoacidosis or hyperosmolar hyperglycemic state, or were treated with GLP-1 receptor agonists during the three months prior to admission. Those who had recurrent severe hypoglycemia, clinically relevant liver disease, low estimated glomerular filtration rate, or gastrointestinal complications were also excluded.
Mean daily BG was similar between patients treated with exenatide plus basal and a basal-bolus regimen (154 ± 39 vs. 166 ± 40 mg/dL, and exenatide plus basal resulted in lower daily BG than did exenatide used alone (177 ± 41 mg/dL). Exenatide plus basal resulted in a higher proportion of BG levels in target range between 70 and 180 mg/dL compared with exenatide and basal-bolus (78 percent vs. 62 perent and 63 percent respectively).
As expected by the investigators, more patients in the exenatide and exenatide plus basal groups experienced gastrointestinal side effects such as nausea or vomiting than in the basal-bolus group, with three patients discontinuing exenatide due to adverse events. While patients in the exenatide arms of the study experienced lower rates of hypoglycemia, those results did not reach statistical significance in this study. There was no difference in length of stay among the three groups.
Optimizing Inpatient Diabetes Care
The goal of the study was to get to a more optimal state of diabetes care in the hospital. However, inpatient studies are challenging because they create an extra set of complexities—patients are out of their normal environment and it can be a stressful experience. By using stringent exclusion criteria, the investigators avoided exposing patients to unnecessary risk.
“We need to be more open to trying new things in the hospital,” Mize said. “There are newer agents and newer technologies we hope to study in a controlled setting.” These include a new class of diabetes medication, SGLT-2 inhibitors, which has some cardiovascular benefits, and technologies for monitoring glucose without the minimum four finger pricks per day required in the hospital.
“It’s not just about which medications to use, but what is the best way to provide diabetes care for our patients in the hospital,” Mize said. “We’re trying to develop safer and more effective therapies and reduce the burden on the patient.”
