Changes in Bone Turnover With Exposure to a GLP-1 Receptor Agonist
Condition: Type 2 Diabetes Mellitus; Bone Remodeling
MeSH terms: Diabetes Mellitus, Type 2
Intervention: exenatide; Saline
Intervention description: exenatide 5mcg sq twice daily for one month and exenatide 10mcg twice daily for month 2. The 3rd month is a washout period. Month 4 and 5 saline placebo is given as 5mcg and 10mcg respectively.; Month 1 and 2 saline placebo is given as a low and high dose respectively. The 3rd month is a washout period. Month 4 exenatide 5mcg sq twice daily and for month 5 exenatide 10mcg twice daily is administered.
Intervention MeSH terms: Exenatide
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Enrollment: 14.0
Sex: Female
Minimum age: 45 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Type 2 diabetes; exenatide; Byetta

Summary:

      The purpose of this study is to determine changes in bone turnover markers and calcitonin
      following the initiation of exenatide compared to placebo in postmenopausal women wtih type 2
      diabetes.

      Hypothesis 1a: Bone resorption (measured by osteocalcin and bone-specific alkaline
      phosphatase) will be lower and bone formation (measured by type I collagen crosslinked
      aminoterminal peptide in urine (Urine NTX)) will be higher when subjects are treated with
      exenatide compared to when subjects are treated with placebo.

      Hypothesis 1b: Calcitonin levels will not vary significantly between periods of treatment
      with exenatide vs. placebo.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Postmenopausal women (as defined by age ≥45 years old or amenorrhea for >2years)

          -  Type 2 DM currently not on diabetes-specific medication(s) or treated with monotherapy
             of metformin or a sulfonylurea. Patients treated with insulin monotherapy will also be
             eligible if the total daily dose of insulin is ≤10units. If on a medication for
             diabetes prior to study entry, the medication can be discontinued for 2 weeks prior to
             study initiation.

          -  Hemoglobin A1c (HbA1c) of 6.5-9.0%

        Exclusion Criteria:

          -  Use of an incretin mimetic (i.e. exenatide, liraglutide), a DPP-4 inhibitor (i.e.
             sitagliptin, saxagliptin), a thiazolidinedione, or oral glucocorticoids in the 6
             months prior to the study will not be eligible

          -  Known osteoporosis or patients treated with an osteoporosis-specific medication
             (bisphosphonate, teriparatide) or estrogen (including Selective Estrogen Receptor
             Modulators (SERMs)) or those who anticipate imminent treatment with one of these
             medications will be excluded from the study

          -  Chronic kidney disease (calculated GFR <30 ml/min) or a disease known to affect bone
             turnover (i.e. Paget Disease, Osteogenesis Imperfecta, HIV) will be excluded from the
             study.

          -  History of pancreatitis