Safety and tolerability of exenatide once weekly in patients with type 2 diabetes: an integrated analysis of 4,328 patients - PubMed (original) (raw)
Safety and tolerability of exenatide once weekly in patients with type 2 diabetes: an integrated analysis of 4,328 patients
Leigh MacConell et al. Diabetes Metab Syndr Obes. 2015.
Abstract
Background: Exenatide once weekly (QW) is a glucagon-like peptide-1 receptor agonist (GLP-1RA) for the treatment of type 2 diabetes. Safety and tolerability are key considerations in treatment selection. This analysis examines the safety and tolerability profile of exenatide QW, other approved GLP-1RAs (exenatide twice daily and liraglutide once daily), and a pooled population of commonly used non-GLP-1RA treatments.
Methods: Intent-to-treat populations from eight randomized Phase III trials with 24-week and 30-week comparator-controlled periods were analyzed. Data were pooled for exenatide QW, exenatide twice daily, and non-GLP-1RA comparator groups; comparisons between exenatide QW and liraglutide were analyzed separately to better match study groups. The incidence of treatment-emergent adverse events with 95% confidence intervals and exposure-adjusted incidence were calculated. Duration and recurrence were analyzed for gastrointestinal adverse events and adverse events of special interest.
Results: Incidences of serious adverse events did not differ between treatments. Discontinuations due to adverse events occurred numerically less frequently with exenatide QW than with other GLP-1RAs but numerically more frequently than with non-GLP-1RA comparators. The most frequent adverse events in the GLP-1RA groups were gastrointestinal and generally mild, with decreasing incidence over time. Gastrointestinal adverse event incidences appeared lower with exenatide QW versus other GLP-1RAs and greater than with non-GLP-1RA comparators. Injection site-related adverse events seemed highest with exenatide QW, but generally did not lead to withdrawal and abated over time. Hypoglycemia was infrequent overall, but occurred numerically more frequently in the non-GLP-1RA comparator group and increased with concomitant sulfonylurea use. Pancreatitis, thyroid cancer, renal failure, and gallbladder disease were rarely reported.
Conclusion: The overall safety and tolerability profile of exenatide QW was similar to that of other GLP-1RAs, with improved gastrointestinal tolerability. The safety and tolerability profile of exenatide QW compared with non-GLP-1RA comparators was similar overall, with the exception of a lower incidence of hypoglycemia and anticipated differences in gastrointestinal and injection site-related adverse events.
Keywords: adverse events; glucagon-like peptide-1 receptor agonist; hyperglycemia; hypoglycemia.
Figures
Figure 1
Selection of trials for pooled analysis and patient disposition. Of the 16 completed clinical trials with available data, eight comparator-controlled studies were included. Abbreviations: ITT, intent-to-treat; Met, metformin; QW, once weekly; SFU, sulfonylurea; TZD, thiazolidinedione; DURATION, Diabetes Therapy Utilization: Researching Changes in A1C, Weight, and Other Factors Through Intervention With Exenatide Once Weekly.
Figure 2
Incidence and duration of gastrointestinal-related adverse events over time. Incidence (left panel) and duration (right panel) for (A, B) nausea, (C, D) vomiting, and (E, F) diarrhea in each treatment group. Duration of the nausea/vomiting event is calculated as the resolution date (or the last participation date if event is ongoing at the time of study termination) minus the event onset date plus 1. aEvents lasting longer than 7 days in duration included reports of both continuous and intermittent nausea/vomiting. 95% confidence interval for the difference (exenatide QW incidence [%] minus liraglutide QD incidence [%] in DURATION-6). Abbreviations: BID, twice daily; QD, once daily; QW, once weekly; DURATION, Diabetes Therapy Utilization: Researching Changes in A1C, Weight, and Other Factors Through Intervention With Exenatide Once Weekly.
Figure 3
Occurrence of gastrointestinal-related adverse events over time with exenatide QW treatment. Incidences of nausea, vomiting, and diarrhea in patients treated with exenatide QW are combined for weeks 0–12 in 2-week increments.– Abbreviation: QW, once weekly.
Figure 4
Incidence of hypoglycemia by treatment and use of SFU. Percentage of patients who experienced minor hypoglycemia. 95% confidence interval of the difference (exenatide QW incidence [%] minus liraglutide QD incidence [%] in DURATION-6). Abbreviations: BID, twice daily; QD, once daily; QW, once weekly; SFU, sulfonylurea; DURATION, Diabetes Therapy Utilization: Researching Changes in A1C, Weight, and Other Factors Through Intervention With Exenatide Once Weekly.
Figure 5
Adverse events of interest. Exposure-adjusted incidence per 100 patient-years and difference in thyroid neoplasm, pancreatitis, renal failure, and gallbladder disease. Pancreatitis includes acute pancreatitis and chronic pancreatitis. Thyroid neoplasm includes benign neoplasm of the thyroid gland and malignant thyroid neoplasm. 95% confidence interval for the difference (exenatide QW incidence [%] minus liraglutide QD incidence [%] in DURATION-6). Abbreviations: BID, twice daily; QD, once daily; QW, once weekly; DURATION, Diabetes Therapy Utilization: Researching Changes in A1C, Weight, and Other Factors Through Intervention With Exenatide Once Weekly.
References
- American Diabetes Association Standards of medical care in diabetes – 2015. Diabetes Care. 2015;38(Suppl 1):S1–S94. -PubMed
- Inzucchi SE, Bergenstal RM, Buse JB, et al. Management of hyperglycemia in type 2 diabetes, 2015: a patient-centered approach: update to a position statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care. 2015;38(1):140–149. -PubMed
- Blonde L, Russell-Jones D. The safety and efficacy of liraglutide with or without oral antidiabetic drug therapy in type 2 diabetes: an overview of the LEAD 1–5 studies. Diabetes Obes Metab. 2009;11(Suppl 3):26–34. -PubMed
- Grimm M, Han J, Weaver C, et al. Efficacy, safety, and tolerability of exenatide once weekly in patients with type 2 diabetes mellitus: an integrated analysis of the DURATION trials. Postgrad Med. 2013;125(3):47–57. -PubMed
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