title: Exenatide added to insulin therapy: a retrospective review of clinical practice over two years in an academic endocrinology outpatient setting.
abstract: BACKGROUND
  Exenatide is an antidiabctic agent currently indicated as adjunctive therapy with oral agents for the treatment of type 2 diabetes mellitus (T2DM). Limited published data exist on the off-label use of exenatide in conjunction with insulin in the treatment of T2DM.
  
  
  OBJECTIVE
  The aim of this retrospective study was to examine the effects of exenatide on glycemic control, weight, and insulin dose in patients with T2DM treated with insulin.
  
  
  METHODS
  Patients with T2DM receivirg insulin and adjuvant therapy with exenatide at an endocrinology clinic at a university hospital for up to 27 months were eligible for inclusion. Glycosylated hemoglobin (HbA(1c)), weight, insulin doses (total, prandial, and basal), concurrent oral antidiabetic medications, and adverse events were ascertained by retrospective review of medical records and were considered the clinical parameters of interest. The last observation in 4 specified time intervals (0-6, 6-12, 12-18, and 18-27 months) for each clinical parameter was used in the analysis.
  
  
  RESULTS
  Of the 3397 patients with a confirmed diagnosis of T2DM who were seen at the clinic during the study period, 268 patients met inclusion criteria and were enrolled in the study. Of the 268 patients enrolled, 38 discontinued therapy within the first 2 months, 30 were lost to follow-up, and 12 did not have evaluable data. These latter patients without sufficient data (n = 42) were not included in the primary analysis but were included in the adverse events analysis. Overall, data from 188 patients (mean [SD] age, 56 (9) years; 85 [45%] men; body mass index, 40.4 [8.4] kg/m(2); 160 [85%] white) were evaluated (mean duration of treatment, 350 [208] days) and included in all analyses. The mean baseline values for HbA(1c), weight, and total daily insulin dose before exenatide therapy were 8.05% (1.47%), 117.8 (24.7) kg, and 99.9 (90.0) U, respectively. For the 4 time intervals, the mean changes in HbA(1c) were: -0.66% (1.54%) at 0 to 6 months (P < 0.001); -0.55% (1.4%) at 6 to 12 months (P < 0.001); -0.54% (1.83%) at 12 to 18 months (P = 0.019); and -0.54% (1.37%) at 18 to 27 months (P = 0.020). Mean weight significantly declined with increasing treatment duration. Mean changes in weight were: -2.4 (5.1) kg at 0 to 6 months (P < 0.001); -4.3 (7.2) kg at 6 to 12 months (P < 0.001); -6.2 (9.7) kg at 12 to 18 months (P < 0.001); and -5.5 (10.8) kg at 18 to 27 months (P < 0.01). After 18 months, an increase in weight was observed; but the increase remained lower than baseline. The mean insulin total daily dose (TDD) was decreased in all patients at the 0- to 6-month (-18.0 [49.9] U; P < 0.001) and the 6- to 12-month (-14.8 [35.3] U; P < 0.001) intervals. Mean changes in insulin TDD during the 12- to 18-month and 18- to 27-month intervals were not statistically significant. The mean percent change from baseline in the basal insulin dose at 0 to 6 months, 6 to 12 months, 12 to 18 months, and 18 to 27 months was not statistically significant. For the 4 intervals, the mean percent change from baseline in the prandial insulin dose was -33.5% (56.2%) at 0 to 6 months (P < 0.001); -25.9% (59.7%) at 6 to 12 months (P = 0.002); -29.7% (74.8%) at 12 to 18 months (P = 0.02); and -55.7% (56.8%) at 18 to 27 months (P = 0.005). Of the 226 patients who were treated with exenatide + insulin for any length of time (including within the first 2 months), 59 (26.1%) discontinued exenatide because of adverse events. The adverse events were largely considered mild and included nausea (n = 51 [22.6% of patients]), vomiting (22 [9.7%]), hypoglycemia (9 [4.0%]), heartburn (2 [0.9%]), diarrhea (1 [0.4%]), constipation (1 [0.4%]), malaise (1 [0.4%]), and generalized edema (1 [0.4%]). Two serious adverse events occurred during the study period: acute renal failure not attributed to exenatide (1 [0.4%]); and pancreatitis (1 [0.4%]), both of which required hospitalization 1 month after the start of exenatide therapy.
  
  
  CONCLUSIONS
  In this retrospective review of patients with T2DM treated in an outpatient setting, the addition of exenatide to insulin-based therapy was associated with reductions in mean HbA(1c), weight, and prandial insulin requirements for treatment periods of up to 27 months, and in total insulin requirements for treatment periods of up to 12 months.
authors.affiliation: Division of Endocrinology and Metabolism, School of Medicine, Indiana University, Indianapolis, Indiana 46202, USA.
authors.forename: Nancy M
authors.initials: NM
authors.lastname: Yoon
authors.forename: Melissa K
authors.initials: MK
authors.lastname: Cavaghan
authors.forename: Rocco L
authors.initials: RL
authors.lastname: Brunelle
authors.forename: Paris
authors.initials: P
authors.lastname: Roach
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000553:Ambulatory Care; D001786:Blood Glucose / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D000077270:Exenatide; D005260:Female; D005500:Follow-Up Studies; D006442:Glycated Hemoglobin / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007328:Insulin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D012189:Retrospective Studies; D013997:Time Factors; D014688:Venoms / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D001786:Blood Glucose; D000077270:Exenatide; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D010455:Peptides; D014688:Venoms