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.
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.
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.
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  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. Conclusion: 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.
SourceAvailable from: Michael P KaneThe Journal of pharmacy technology: jPT: official publication of the Association of Pharmacy Technicians 07/2014; 30(4):118-124. DOI:10.1177/8755122513518189
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ABSTRACT: Background Weight gain and hypoglycaemia are common adverse effects associated with anti-diabetic treatments. AimsTo evaluate the long-term effects of adjunctive exenatide therapy on weight loss and glycemic control in patients with type 2 diabetes. MethodsA review of medical records in a specialist diabetes clinic over 5 years identified 446 patients who were prescribed exenatide therapy. We examined change in glycosylated haemoglobin (HbA1c), weight, albumin creatinine ratio and hypoglycaemic medication during 24 months follow-up. ResultsSubjects were aged 59 ± 10 years (49% women) and received exenatide in combination with oral agents and insulin (47%). During an average of 17 ± 14 months follow-up, 51% (more women than men [OR 1.69, 95% CI 1.14-2.49]) remained on treatment. Lack of efficacy (33%) and/or gastrointestinal (27%) side effects were the main reasons for treatment cessation. At 24 months, there was a reduction in HbA1c of 0.7 ± 1.2% and weight loss of 4.3 ± 5.2 kg. Change in HbA1c was similar regardless of concurrent insulin therapy, yet insulin was associated with greater weight reduction (4.8 ± 5.3 versus 3.8 ± 5.1 kg, p=0.016). Independent predictors of HbA1c response were higher baseline HbA1c, longer duration of diabetes and use of insulin or sulfonylureas at study end. Predictors of weight response were baseline use of insulin or thiazolidinediones, increased age, female sex and sulfonylurea or thiazolidinediones at study end. Longer exenatide treatment duration was favourable for reducing HbA1c and weight. Conclusions Exenatide is effective in reducing HbA1c and weight, regardless of concurrent insulin, and in a specialist diabetes outpatient clinic, is recommended for use in clinical practice.Internal Medicine Journal 02/2014; 44(4). DOI:10.1111/imj.12377
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ABSTRACT: Real-world data on emerging combination approaches for type 2 diabetes mellitus (T2DM) management are limited. The objective of the current study was to document the characteristics and clinical outcomes of patients with T2DM initiating prandial insulin or a glucagon-like peptide-1 (GLP-1) receptor agonist while on basal insulin. This was a retrospective analysis of an electronic medical records database of patients with T2DM managed in a community practice setting in the United States. The main outcome measures were glycated hemoglobin (HbA1c), body weight, hypoglycemia, and health care resource utilization at baseline and at 6-month and 1-year follow-up. A total of 33 810 patients were included in the study: 31 848 on prandial insulin and 1962 on a GLP-1 receptor agonist. At baseline there were significant differences in mean age (60 vs 56 years), mean Charlson Comorbidity Index score (1.1 vs 0.7), mean HbA1c (8.8% vs 8.4%), and mean body weight (99 vs 112 kg) between the prandial insulin and GLP-1 receptor agonist groups, respectively (P < 0.001 for each). After matching for baseline differences, significant and similar changes from baseline were observed between the prandial insulin and the GLP-1 receptor agonist groups during follow-up at the 6 months/1 year post-index date for HbA1c (-0.45/-0.60% vs -0.44/-0.58%, respectively; P = 0.907/0.723 between groups). Body weight changes between the groups were significantly different at 6 months/1 year (+1.7/-1.7 vs -0.9/-3.7 kg; P < 0.001). Hypoglycemia incidence and health care resource utilization were significantly greater in the prandial insulin versus GLP-1 receptor agonist group. The results of this real-world analysis of patients with T2DM adding a GLP-1 receptor agonist or prandial insulin to basal insulin suggest an association between adding a GLP-1 receptor agonist with similar glycemic control, greater reduction in body weight, lower hypoglycemia incidence, and lower health care utilization compared with adding prandial insulin.Postgraduate Medicine 10/2014; 126(6):49-59. DOI:10.3810/pgm.2014.10.2820