Changes in Bone Turnover With Increased Incretin Hormone Exposure (DRTC)
|ClinicalTrials.gov Identifier: NCT01374568|
Recruitment Status : Terminated (Study closed by sponsor. Funding ended.)
First Posted : June 16, 2011
Results First Posted : May 31, 2017
Last Update Posted : July 24, 2017
|Condition or disease||Intervention/treatment||Phase|
|Type 2 Diabetes Mellitus||Drug: sitagliptin Other: Placebo||Phase 4|
Patients with Type 2 Diabetes Mellitus (T2DM) are at an increased risk of fracture, despite having bone mineral density (BMD) similar to age and sex matched cohorts. Recent studies have indicated that changes in incretin (INtestinal seCRETion of INsulin) hormones in the setting of T2DM may play a role in bone metabolism. Two of these incretin hormones, gastric inhibitory polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), have been shown to be involved in bone turnover regulation, in addition to their effect in increasing insulin secretion and decreasing glucagon secretion in a glucose-dependent manner. In addition, the rise in glucagon-like peptide-2 (GLP-2) in the postprandial state has been found to have a direct effect on reduced bone resorption in a non-fasting state and treatment with GLP-2 improved BMD in postmenopausal women. Due to their glucose lowering effects, incretins have been a therapeutic target for the treatment of T2DM through GLP-1 receptor analogs or inhibition of incretin metabolism via dipeptidyl peptidase 4 (DPP-4) inhibitors (i.e. sitagliptin). Inhibition of DPP-4 leads to an approximate doubling of GLP-1 and GIP levels but also leads to reduced breakdown of GLP-2.
Less is known about the effect of incretin-directed therapies, specifically sitagliptin, and bone metabolism. To our knowledge, two studies have looked at the direct effects of currently available incretin-directed therapies on bone metabolism. Exenatide (a GLP-1 analog) treatment of insulin resistant and type 2 diabetic rats resulted in osteogenic effects with increased osteocalcin levels following treatment. In a study of female non-diabetic Sprague-Dawley rats treated with pioglitazone, rosiglitazone, sitagliptin, vs. placebo, no significant change in bone mineral density was seen in the sitagliptin or placebo treated rats (compared to significant loss of bone mineral density in the TZD groups). Even fewer published studies are available evaluating changes in bone metabolism with the use of incretin hormones in humans. The majority of the human studies have been completed with GLP-2. These studies show a dose-dependent effect of GLP-2 on bone resorption and, preliminarily, show improved bone mineral density in postmenopausal women treated with GLP-2. However, the changes in incretin activity vary in persons with glucose intolerance and T2DM. Therefore, it is important to understand the potential effects of these medications on bone metabolism in persons prescribed these medications for treatment of their T2DM.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||6 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Double (Participant, Investigator)|
|Primary Purpose:||Health Services Research|
|Official Title:||Changes in Bone Turnover With Increased Incretin Hormone Exposure (UAB Diabetes Research and Training Center Pilot and Feasibility Study)|
|Study Start Date :||July 2010|
|Primary Completion Date :||July 6, 2012|
|Study Completion Date :||September 2015|
Active Comparator: sitagliptin
sitagliptin 100mg daily
Other Name: Januvia
Placebo Comparator: Placebo
1 pill daily
- Bone Turnover in Subjects Treated With Sitagliptin When Compared to Those Treated With Placebo. [ Time Frame: 8 weeks ]Bone turnover assessed using change in TRACP5b over 8 weeks of treatment.
- Bone Turnover in Subjects Treated With Sitagliptin When Compared to Those Treated With Placebo [ Time Frame: 8 WEEKS ]Bone turnover assessed using change in bone-specific alkaline phosphatase (BAP) over 8 weeks of treatment.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01374568
|United States, Alabama|
|University of Alabama at Birmingham|
|Birmingham, Alabama, United States, 35294|
|Principal Investigator:||Amy Warriner, MD||University of Alabama at Birmingham|