A Cohort Study of the Benefits of Bydureon in Customary Clinical Care in the United States - Additional Analyses
Trial Snapshot
- Phase
- Not Applicable
- Status
- Completed
- Sponsor
- AstraZeneca
- Enrollment
- 6,024
- Locations
- 1
- Primary Endpoint
- Changes from baseline in weight (kg)
Study Overview
Brief Summary
Exenatide once weekly (Bydureon) was approved in January 2012 by FDA in USA for the treatment of type 2 diabetes mellitus. Evidence from clinical trials suggested that Bydureon improves glucose control with low risk of hypoglycemia. Bydureon does not require a dose titration as necessary for other glucagon-like peptide-1 agonists, and appears to have other advantages, such as reducing insulin resistance, reducing weight, and improving blood pressure and lipid profiles. However, the degree to which these advantages of Bydureon lead to improve outcomes in customary clinical care in patients with mild and moderate renal impairment and in elderly patients are unknown.
The aim of this study is to evaluate the effectiveness and tolerability of Bydureon relative to basal insulin initiated as first-ever injectable therapeutic regimens among elderly patients and patients with renal impairment. Patients who initiated treatment with Bydureon or basal insulin between July 2011 and March 2015 will be recruited into the study cohorts from Optum's database of electronic health records. The two treatment cohorts will be matched by propensity score method. Changes in HbA1c, weight, markers for renal function (estimated glomerular filtration rate (eGFR), serum creatinine, and albumin/creatinine ratio (ACR)), and incidences of gastrointestinal symptoms and hypoglycaemia are investigated for patients with different eGFR categories and with different ages.
Detailed Description
Background: In January 2012, the US Food and Drug Administration approved a once-weekly form of exenatide, Bydureon, for the treatment of type 2 diabetes mellitus. Evidence from clinical trials suggested that Bydureon improves glucose control with low risk of hypoglycemia. Bydureon does not require a dose titration as necessary for other glucagon-like peptide-1 agonists (GLP-1RAs), and appears to have other advantages, such as reducing insulin resistance, reducing weight, and improving blood pressure and lipid profiles. However, the degree to which these advantages of Bydureon lead to improve outcomes in patients with renal impairment or who are elderly is unknown.
Aims: The aim of this study is to evaluate the effectiveness and tolerability of Bydureon relative to basal insulin initiated as first-ever injectable therapeutic regimens among elderly patients and patients with renal impairment.
The specific study objectives are as follows:
- To quantify the effectiveness of Bydureon initiation relative to initiation of basal insulin, on improving:
- Glycated hemoglobin (HbA1c)
- Weight (body mass index (BMI))
- HbA1c simultaneous to reduction in weight
- Blood pressure and lipid profiles
- To examine the tolerability of Bydureon initiation relative to initiation basal insulin, on the occurrence of :
- Hypoglycemia
- Gastrointestinal symptoms (nausea, vomiting, diarrhea, and constipation)
- Change in the markers for renal function (estimated glomerular filtration rate (eGFR), serum creatinine, and albumin/creatinine ratio (ACR), and the stability of liver function test (AST, ALT) and standard blood counts (WBC, RBC, HCT, Hgb, PLT)
- To examine these measures of effectiveness and tolerability within potentially vulnerable subgroups of Bydureon and basal insulin initiators:
- T2D patients with renal impairment
- Elderly T2D patients Study Population and Design: This retrospective cohort study will use Optum's EHR data from July 2011 through March 2015 and identify injectable-naive T2D patients who initiated either Bydureon or basal insulin during the accrual period, January 2012 and January 2015. Injectable-naive T2D patients will be indetified. Propensity score methods will be used to match Bydureon initiators with basal insulin initiators.
Subgroup Comparisons: Within the EHR data, serum creatinine values will be used to calculate the eGFR using an equation developed by the Chronic Kidney Disease (CKD) Epidemiology (EPI) Collaboration, called the CKD-EPI Equation.
Study Design
- Study Type
- Observational
- Observational Model
- Cohort
- Time Perspective
- Retrospective
Eligibility Criteria
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •At least 18 years old;
- •had received care documented in EHR (including at least one out-patient provider visit) for a minimum of 6-months prior index date;
- •had at least one diagnosis of Type 2 diabetes (ICD-9-CM: 250.X0 or 250.X2) prior to and including the date of the study drug initiation, with no prior diagnosis of type1 diabetes (ICD-9-CM: 250.X1 or 250.X3), or gestational diabetes within the 6-months prior to index date;
- •No evidence of prior injectable antidiabetic treatment, specifically no dispensing of a GLP-1-RA or any insulin during the 6-months baseline period prior to study drug initiation
Exclusion Criteria
- •Prior diagnosis of type 1 diabetes (ICD-9-CM: 250.X1 or 250.X3), or gestational diabetes within the 6-months prior to index date;
- •Prior dispensing of a GLP-1RA or any insulin
- •Missing data on renal function defined by eGFR or age
Arms & Interventions
Exenatide once weekly initiators
Type 2 diabetes patients who initiated exenatide once weekly treatment during the index period
Intervention: exenatide once weekly (Drug)
Basal Insulin initiator cohort
Type 2 diabetes patients who initiated basal insulin treatment in the index period
Intervention: basal insulin (Drug)
Outcomes
Primary Outcomes
Changes from baseline in weight (kg)
Time Frame: one year post-index
To evaluate changes in weight (kg) from baseline after initiation of therapy with exenatide once-weekly in patients with different renal functions or age classes, as referred to basal insulin initiators of the same subgroups.
Changes from baseline in HbA1c (%)
Time Frame: one year post-index
To evaluate changes in HbA1c (%) from baseline after initiation of therapy with exenatide once-weekly in patients with different renal functions or age classes, as referred to basal insulin initiators of the same subgroups.
Secondary Outcomes
- Changes from baseline in eGFR(one year post-index)
- Frequency of Hypoglycemia(one year post-index)
- Frequency of Nausea(one year post-index)
- Frequency of Vomiting(one year post-index)