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Bone Turnover in Type 2 Diabetes Patients

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00732121
Recruitment Status : Unknown
Verified February 2009 by University of Vermont.
Recruitment status was:  Active, not recruiting
First Posted : August 11, 2008
Last Update Posted : June 28, 2010
Merck Sharp & Dohme Corp.
Information provided by:
University of Vermont

Brief Summary:


Incretin hormones are hormones produced by the gut in response to food intake. These hormones help the body to control the metabolism of glucose (sugar). In particular, two incretin hormones (GLP-1 and GIP) cause the pancreas to secrete more insulin in response to high blood glucose levels. This helps the body to metabolize the glucose more effectively, lowering blood sugar levels. In addition to their effects on the pancreas, GLP-1 and GIP have effects on other tissues, including the brain, gut, fat cells and bone. A new class of oral drugs developed for the treatment of type 2 diabetes mellitus (T2DM) called DPP-4 inhibitors increases levels of the active forms of GLP-1 and GIP in the body by preventing their breakdown. This study tests whether a medicine in this class called sitagliptin (Januvia), which is commonly used to treat T2DM, affects markers of bone turnover in patients with T2DM. The hypothesis is that treatment with sitagliptin will increase markers of bone formation and decrease markers of bone resorption during a mixed meal, by enhancing active circulating levels of GLP-1, GIP and GLP-2.


To address this question we will recruit patients with T2DM whose diabetes is controlled with either diet+exercise or with metformin (another medicine commonly used to treat T2DM). Subjects will undergo measurement of body fat and bone mineral density by DEXA scanning and a 3-hour mixed meal test. During the mixed meal test blood samples will be taken to measure how much GLP-1 and GIP are produced. Markers of bone formation will also be measured in blood samples obtained during the mixed meal test. Subjects will then be randomly assigned to 8 weeks of treatment with either sitagliptin (100 mg/day) or matching placebo (an inactive tablet that does not contain medication). Subjects will be seen 4 weeks after commencing treatment to assess safety and tolerability. After 8 weeks of treatment the meal test will be repeated. Subjects will then be washed off of their initial treatment (sitagliptin or placebo) for 1 week (that is, they will receive no study medication during this period). After the washout period, they will commence a second 8-week period of treatment with the other study medication (that is, if they received sitagliptin initially, they will receive placebo during period 2 and vice-versa). At the end of period 2, subjects will undergo a third mixed meal test with measurement of GLP-1, GIP and markers of bone turnover.


Recent studies suggest that oral antidiabetic medications of the thiazolidinedione class, such as rosiglitazone (Avandia) and pioglitazone (Actos), may weaken bones, increasing the risk of fractures in older women with diabetes. The proposed study will test whether drugs of the DPP-4 inhibitor class, such as sitagliptin (Januvia), have beneficial effects on bone turnover by increasing the activity of GLP-1 and GIP. Results of this pilot study may suggest the need to perform longer-term studies to determine whether DPP-4 inhibitors increase bone mineral density and reduce the risk of fractures in patients with diabetes.

Condition or disease Intervention/treatment Phase
Type 2 Diabetes Drug: Sitagliptin Drug: Placebo Phase 4

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: Effects of Sitagliptin On Markers of Bone Turnover in Patients With Type 2 Diabetes
Study Start Date : August 2008
Estimated Primary Completion Date : June 2010
Estimated Study Completion Date : August 2010

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Active Comparator: 1
Drug: Sitagliptin
100 mg daily for 4 weeks
Other Name: Januvia (brand name for sitagliptin)

Placebo Comparator: 2
Placebo arm
Drug: Placebo

Primary Outcome Measures :
  1. Change from baseline in the integrated response to the mixed meal test of markers of bone turnover following 8 weeks of treatment with sitagliptin vs. placebo. [ Time Frame: 8 weeks per subject ]

Secondary Outcome Measures :
  1. Change in the active GIP in response to the mixed meal test [ Time Frame: 8 weeks ]
  2. Change in the active GLP-1 in response to the mixed meal test. [ Time Frame: 8 weeks ]
  3. Change in the active GLP-2 in response to the mixed meal test. [ Time Frame: 8 weeks ]
  4. Change in glucose response during the mixed meal test. [ Time Frame: 8 weeks ]
  5. Change in insulin secretion during the mixed meal test. [ Time Frame: 8 weeks ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Type 2 diabetes treated with diet/exercise or metformin
  • HbA1c less than or equal to 7%
  • Men and women aged 45-80 years old
  • If female, must be post-menopausal (natural or surgical)

Exclusion Criteria:

  • Endocrine disorders (acromegaly, anorexia, Cushings, type 2 diabetes, hyperparathyroidism, hyperthyroidism, hypercalcemia)
  • GI conditions (celiac sprue, gastric bypass/gastrectomy, active inflammatory bowel disease, cirrhosis)
  • Cancer (including multiple myeloma) within 3 years of the study (except local non-melanoma skin cancers and cervical carcinoma in situ)
  • Active alcoholism or drug abuse
  • Chronic kidney disease with a GFR < 60
  • History of hypersensitivity reaction to sitagliptin or other DPP-4 inhibitors
  • Hemoglobin < 12 mg/dL for men and < 10 for women
  • Taking medications that could affect bone turnover (estrogen, progesterone, testosterone, bisphosphonates, SERMS, calcitonin, teriparatide cyclosporine glucocorticoids, methotrexate or phenothiazines), thiazolidinediones, sulfonylureas, dipeptidyl peptidase-4 inhibitors, exenatide, insulin, weight loss drugs

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00732121

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United States, Vermont
University of Vermont
South Burlington, Vermont, United States, 05403
Sponsors and Collaborators
University of Vermont
Merck Sharp & Dohme Corp.
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Principal Investigator: Richard E Pratley, MD University of Vermont
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Responsible Party: Richard Pratley, MD, University of Vermont College of Medicine Identifier: NCT00732121    
Other Study ID Numbers: Merck-33283
First Posted: August 11, 2008    Key Record Dates
Last Update Posted: June 28, 2010
Last Verified: February 2009
Keywords provided by University of Vermont:
Type 2 Diabetes
Additional relevant MeSH terms:
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Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Sitagliptin Phosphate
Hypoglycemic Agents
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action