Original ResearchOnce-Weekly Exenatide as Adjunct Treatment of Type 1 Diabetes Mellitus in Patients Receiving Continuous Subcutaneous Insulin Infusion Therapy
Introduction
The control of glucose homeostasis in patients with type 1 diabetes is difficult as their beta-cell function is negligible. The deficiency in generating insulin or amylin in these patients leads to an inability to naturally compensate for their variable physiological insulin requirements and suppress postprandial glucagon. Their exogenous insulin boluses injected may not match their dosage requirements and bioavailability. Furthermore, in the near absence of insulin and amylin secretion by beta cells, the physiological postprandial inhibition of glucagon secretion by alpha cells likely does not occur in patients with type 1 diabetes, leading to hyperglucagonemia 1, 2. Currently, there are limited data available regarding postprandial glucagon secretion and incretin pathophysiology in patients with type 1 diabetes 1, 3. It is essential that this area be investigated further as the erratic and often uncontrollable patterns of glucose concentrations in these patients may be due to hyperglucagonemia 1, 2.
Clinically, there is a well-established role for the use of incretin mimetics in patients with type 2 diabetes. However, it is only recently that small studies have begun exploring the role of glucagon-like peptide-1 (GLP-1) agonists in patients with type 1 diabetes. Dupré et al (3) showed that activation of the GLP-1 receptor improves postprandial hyperglycemia in patients with type 1 diabetes, possibly through the suppression of glucagon secretion. Similarly, Raman et al (4) demonstrated a reduction in postprandial glucose after a single twice-daily exenatide injection in adolescents with type 1 diabetes. Kielgast et al (5) demonstrated that a month of treatment with liraglutide (titrated up to 1.2 mg daily after 1 week of 0.6 mg daily) reduced insulin doses without a negative impact on overall glycemic control in patient with type 1 diabetes. Most recently, Varanasi et al (6) showed improved glucose concentrations and less glycemic excursions in adults with type 1 diabetes within 1 week of starting liraglutide 0.6 mg daily.
The aim of our study was to determine the clinical effects of once-weekly exenatide as add-on therapy to insulin in patients with type 1 diabetes. In addition to enhanced glycemic control, we hypothesized that the administration of once-weekly exenatide would lead to improvements in other markers of diabetes management, such as blood pressure and body weight.
Section snippets
Methods
This retrospective observational study was conducted at an ambulatory care endocrinology office affiliated with the Rochester General Health System located in Rochester, New York. After obtaining appropriate protocol approval from the Institutional Review Boards at both Rochester General Health System and St. John Fisher College, subjects were identified, and all pertinent information was gathered utilizing an electronic medical record system search. Patients with type 1 diabetes aged 18 years
Results
The electronic medical record search identified 101 patients receiving once-weekly exenatide therapy. Of these, 29 patients had type 1 diabetes, and the remaining 72 patients had type 2 diabetes. Eleven of the 29 patients with type 1 diabetes met the remaining study criteria. The average duration of follow up was 90±8 days, mean age was 53±11.1 years, average duration of diabetes was 39 years (range 11 to 49 years), median age at diagnosis was 17 years (range 2 to 54 years), 4 patients used a
Discussion
To our knowledge, this is the first study evaluating the use of once-weekly exenatide as adjunct treatment of patients with type 1 diabetes. Incretin therapy has been shown to reduce glycemic variability, insulin doses or weight in both type 1 diabetes and type 2 diabetes 1, 4, 5, 6, 7, 8. Despite these promising data, incretin therapy for type 1 diabetes is not standard of care. On an individualized basis, patients were prescribed once-weekly exenatide based on clinical indication (glycemic
Acknowledgements
The authors would like to thank Ritu Malik, MD, attending physician, and our Medical Director and Chief Attending Physician Zachary Freedman, MD, FACE, for their assistance and support throughout the project, and Michael Kane, PharmD, FCCP, BCPS, BCACP, for his technical assistance with manuscript preparation.
References (8)
- et al.
Exenatide once weekly versus twice daily for the treatment of type 2 diabetes: a randomized, open-label, non-inferiority study
Lancet
(2008) - et al.
Effect of glucagon-like peptide-1 on alpha- and beta-cell function in C-peptide-negative type 1 diabetic patients.
J Clin Endocrinol Metab
(2010) - et al.
Regulation of pancreatic insulin and glucagon secretion
Annu Rev Physiol
(1976) - et al.
Exendin-4 normalized postcibal glycemic excursions in type 1 diabetics
J Clin Endocrinol Metab
(2004)
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