Participants will be persons with Type 2 Diabetes who are likely to have increased risk of
bone fractures. The investigators believe this medication will enhance bone turnover.
The investigators will use DXA measurements to evaluate bone density before and after
subjects take the medication.
Type 2 Diabetes Mellitus (T2DM) is associated with an increased risk of bone fractures even
when there is not decreased bone density via DXA measurements. This appears primarily
related to impaired bone quality and abnormal bone architecture. Although the exact
pathophysiologic mechanisms remain unclear, low bone turnover is considered one of the key
defects. Emerging evidence suggests that dipeptidyl peptidase (DPP) inhibition is associated
with improved bone quality and reduction in fracture risk.
While animal studies have shown an improvement in bone mineral density and trabecular
architecture with sitagliptin treatment, no such studies in humans have yet been undertaken.
We are proposing to extend these animal studies with a pilot clinical trial that seeks to
use serum markers of bone turn-over and calcaneal quantitative ultrasound to evaluate the
effect of DPP-4 inhibition on bone metabolism. Our hypothesis is that DPP-4 inhibition with
sitagliptin will enhance bone turn over and quality in persons with T2DM.
This project project seeks to examine the impact of six months of therapy on sitagliptin, a
DPP-4 inhibitor, on bone metabolism and bone quality in subjects with T2DM. The proposed
study is intended to be a pilot investigation for providing preliminary data for submission
of a more definitive national grant proposal with a larger patient population, blinded
randomized control design and high resolution CT imaging of the lumbar spine.
1. Type 2 diabetes mellitus.
2. Hemoglobin A1c >6.5% and <10%.
3. Estimated GFR greater than 60 mL per minute per meter squared.
4. Between 18 and 70 years of age.
5. On oral antihyperglycemic agents with stable dose at least for last 2 months.
6. Females: minimum of two years postmenopausal, surgically sterile, or using an
acceptable contraceptive regimen (OCP, IUD, double barrier, Depo-Provera or
subcutaneous progestin implant) and negative urine pregnancy test at trial start.
1. Pregnancy, breast feeding or planning pregnancy during the study period
2. Any medical condition expected to be terminal within one year
3. Active mental illness or other condition which in the opinion of the investigator
would prevent informed consent or adherence with study protocol
4. Use of any PPAR agonist within three months prior to enrollment
5. Daily insulin use
6. Vitamin D level < 20
7. Allergy or intolerance of sitagliptin or other DPP-4 inhibitor
8. Use of DPP-4 inhibitor or GLP-1 analog within three months prior to enrollment
9. Significant alcohol use defined as >3 standard servings of alcohol per day for men
and >2 for women
10. History of bariatric surgery in the last 3 years or planned bariatric surgery during
the study period
11. Receipt of another study drug within 30 days of screening.