Comparison of the Effectiveness and Tolerability of Exenatide Once-weekly Compared to Basal Insulins
Condition: Type 2 Diabetes
MeSH terms: Diabetes Mellitus, Type 2
Study type: Observational

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 is 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 used in customary
      clinical care. 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.Clinical outcomes of HbA1c, weight, and gastrointestinal symptoms and hypoglycemia are
      investigated.
    

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
      receptor agonists (GLP-1RAs), and appears to have other advantages, such as reducing insulin
      resistance, preventing weight gain, and improving blood pressure and lipid profiles. However,
      the degree to which these advantages of Bydureon lead to improve outcomes in customary
      clinical care 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 used in
      customary clinical care.

      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 monitor 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 disease (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 (white blood cell, red blood cell,
           Hematocrit, Hemoglobin, Platelet)

        -  To examine these measures of effectiveness and tolerability within potentially
           vulnerable subgroups of Bydureon and basal insulin initiators:

        -  Type 2 diabetes patients with renal impairment

        -  Elderly Type 2 diabetes patients

        -  Type 2 diabetes patients who are a minority race

        -  Type 2 diabetes patients within strata of HBA1c Design: This retrospective cohort study
           will be conducted using Optum's electronic health record data from July 2011 through
           March 2015 and identified injectable-naive Type 2 diabetes patients who initiated either
           Bydureon or basal insulin during the accrual period, January 2012 and January 2015.
           Injectable-naive Type 2 diabetes patients will be identified. Propensity score methods
           will be used to match initiators of Bydureon to basal insulin initiators.

      Study Population:

      The study population will be selected from the electronic health recrod data included
      patients with Type 2 diabetes who initiated Bydureon or basal insulin. Eligible patients had:

        -  Received care for at least 6 months prior to the date of study drug initiation (cohort
           entry) with at least one outpatient clinic visit in the 6 months prior to cohort entry
           (baseline period);

        -  At least one diagnosis of type 2 diabetes (ICD-9 250.X0 or 250.X2) prior to and
           including the date of the qualifying drug initiation, no prior diagnosis (inclusive of
           the index date) of type 1 diabetes mellitus (250.X1 or 250.X3), and no diagnosis of
           gestational diabetes within the previous 6 months (inclusive of the index date); and

        -  No evidence of prior injectable antidiabetic treatment, specifically no dispensing of
           GLP-1RA or any insulin drug during the 6-month baseline period. Outcomes and Analysis:
           To measure the effectiveness of Bydureon relative to basal insulin are changes in HbA1c
           and body weight, as well as changes in HbA1c and simultaneous reduction in weight.
           Changes in BMI, lipid profiles, and blood pressure will be examined. These variables are
           part of the clinical and laboratory data in the electronic health records. Each outcome
           will be evaluated for completeness, multiply imputed, and reported across standardized
           time intervals. HbA1c, weight and BMI are summarized in baseline and quarterly (3-month
           intervals) in the first year following drug initiation. Lipid measurements and blood
           pressure are summarized in baseline and bi-annually (6-month intervals) in the first
           year following drug initiation.

      To assess drug tolerability, the incidence of hypoglycemia, and gastrointestinal symptoms
      (nausea, vomiting, diarrhea, and constipation) will be assessed. These outcomes are
      ascertained using an ICD-9 algorithm applied to the structured fields and by extracting
      mentions of hypoglycemia using a natural language processing (NLP) algorithm developed by
      Optum and applied to the free text clinical notes available in the data. In addition the
      stability of renal function evaluated by change in eGFR, or albumin/creatinine ratio (ACR);
      the change in serum hepatic enzymes [aspartate aminotransferase (AST), alanine
      aminotransferase (ALT)], and hematologic measures [red blood cells counts (RBC), white blood
      cell counts (WBC), platelets (PLT), hemoglobin (Hgb) and hematocrit (Hct) will be evaluated.
      Each of these laboratory values will be evaluated for completeness, multiply imputed, and
      reported across standardized time intervals. eGFR and ACR will be summarized in baseline and
      quarterly (3-month intervals) in the first year following drug initiation. Hepatic enzymes
      and hematologic measures are summarized in baseline and semi-annually (6-month intervals) in
      the first year following drug initiation.
    

Intervention name(s): exenatide once weekly; basal insulin
Intervention type(s): Drug; Drug
Intervention description(s): exenatide treatment in the customary clinical care in the USA; basal insulin treatment in the customary clinical care in USA
Intervention MeSH terms: Exenatide
Observational model: Cohort
Time perspective: Retrospective
Sampling method: Non-Probability Sample
Study population: 
        This cohort study compares injectable-naive exenatide once-weekly and basal insulin
        initiators. The study cohorts were drawn from an Optum's Electronic Health Records database
        that integrates records from many medical groups and hospitals in the United States
        representing over 25,000 physicians and over 25 million patients in ordinary clinical
        practice. The Electronic Health Records captures clinical, operational, and financial
        information that physicians record at the time of care. This information includes
        diagnoses, procedures, medications (prescribed and administered), clinical measures
        (biometric and laboratory values), and clinical notes (e.g., physician, pathology, and
        radiology notes).
      
Keywords: Type 2 diabetes