Comparison of safety and tolerability with continuous (exenatide once weekly) or intermittent (exenatide twice daily) GLP-1 receptor agonism in patients with type 2 diabetes.
OBJECTIVE
Exenatide is a glucagon-like peptide-1 receptor agonist shown to improve glycaemic control in patients with type 2 diabetes (T2DM). Intermittent exenatide exposure is achieved with the twice-daily formulation (ExBID), while the once-weekly formulation (ExQW) provides continuous exenatide exposure. This integrated, retrospective analysis compared safety and tolerability of ExQW vs. ExBID in patients with T2DM.


METHODS
Data were pooled from two open-label, randomized, comparator-controlled, trials directly comparing ExQW (N = 277) to ExBID (N = 268). Between-group differences in adverse event (AE) and hypoglycaemia incidences were calculated. Incidence over time and duration of selected AEs (nausea, vomiting, and injection-site-related AEs) were also summarized.


RESULTS
The most common AEs were nausea, diarrhoea, injection-site pruritus, and vomiting. Nausea and vomiting occurred less frequently with ExQW vs. ExBID, peaking at initiation (ExQW) or at initiation and dose escalation (ExBID), and decreasing over time. Few patients discontinued because of gastrointestinal-related AEs. Injection-site AEs were more common with ExQW but decreased over time in both groups. No major hypoglycaemia occurred; minor hypoglycaemia occurred with low incidence in patients not using concomitant sulphonylurea, with no difference between ExQW and ExBID. Serious AEs and discontinuations because of AEs were reported with similar frequency in both groups.


CONCLUSIONS
Both exenatide formulations were generally safe and well-tolerated, with ExQW associated with less nausea and vomiting but more injection-site AEs. Continuous vs. intermittent exposure did not impact the overall tolerability profile of exenatide, with no evidence of prolonged duration or worsened intensities of AEs with continuous exposure.
American Health Network, Indianapolis, IN, USA.
T
T
Ridge
T
T
Moretto
L
L
MacConell
R
R
Pencek
J
J
Han
C
C
Schulteis
L
L
Porter
D000368:Aged; D001786:Blood Glucose / Q000187:drug effects*; D001835:Body Weight; D003692:Delayed-Action Preparations; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004334:Drug Administration Schedule; D000077270:Exenatide; D005260:Female; D000067757:Glucagon-Like Peptide-1 Receptor; D006442:Glycated Hemoglobin / Q000187:drug effects*; D006801:Humans; D007003:Hypoglycemia / Q000097:blood / Q000188:drug therapy*; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D010455:Peptides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D018027:Receptors, Glucagon / Q000819:agonists*; D012189:Retrospective Studies; D016896:Treatment Outcome; D014688:Venoms / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D014839:Vomiting / Q000139:chemically induced
D001786:Blood Glucose; D003692:Delayed-Action Preparations; D000077270:Exenatide; D000067757:Glucagon-Like Peptide-1 Receptor; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D010455:Peptides; D018027:Receptors, Glucagon; D014688:Venoms; C000593833:GLP1R protein, human; C517652:hemoglobin A1c protein, human