Effect of Pioglitazone Versus Metformin on Bone Health in Postmenopausal Women With Type 2 Diabetes

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Mohammed-Salleh M. Ardawi, King Abdulaziz University
ClinicalTrials.gov Identifier:
NCT01935804
First received: August 27, 2013
Last updated: June 16, 2014
Last verified: June 2014
  Purpose

The study tests whether pioglitazone (PIO)as compared to metformin (MET)affects bone health including bone mineral density, bone turnover markers, and osteocyte biomarker in patients with type 2 diabetes (T2DM).


Condition Intervention Phase
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Drug: Pioglitazone
Drug: Metformin
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Phase 1 Study of Pioglitazone Versus Metformin on Bone Health in Postmenopausal Women With Type 2 Diabetes

Resource links provided by NLM:


Further study details as provided by King Abdulaziz University:

Primary Outcome Measures:
  • Change in mean percentage change in BMD at various sites by Dual energy X-ray absorptiometry(DXA) from baseline and at 6, 12 months in PIO versus MET treatment group. [ Time Frame: 6-18 months ] [ Designated as safety issue: Yes ]
    The primary endpoint was change in mean percentage change in BMD values at the lumbar spine (L1-L4), femoral neck and total hip by DXA from baseline and at 6 and 12 months in the PIO and the MET treatment groups.


Secondary Outcome Measures:
  • Bone turnover Markers and other Biomarkers [ Time Frame: 6-18 months ] [ Designated as safety issue: Yes ]
    Secondary end-points were changes in serum sclerostin, serum bone-specific alkaline phosphatase (BSAP), serum procollagen type1 N-terminal propeptide (P1NP) and serum C-terminal crosslinking telopeptide of type 1 collagen (CTX); and urinary N-terminal crosslinking telopeptide type 1 collagen (u-NTX); serum calcium, 25-hydroxyvitamin D (25-OHD), and serum Dickkopf-1( DKK-1) at various time intervals from baseline between PIO vs MET treatment.


Other Outcome Measures:
  • Exploratory and Safety Outcomes [ Time Frame: 6-18 months ] [ Designated as safety issue: Yes ]
    Other endpoints were changes in inflammatory markers (hs-CRP)

  • Exploratory Outcomes: lipid profile [ Time Frame: 6-18 months ] [ Designated as safety issue: Yes ]
    lipid profile (total cholesterol, HDL-c, LDL-c and triglycerides)

  • Exploratory outcomes: liver and renal function tests [ Time Frame: 6-18 months ] [ Designated as safety issue: Yes ]
    liver function tests [albumin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP)]; renal function tests (creatinine, urea, uric acid) and parathyroid hormone (PTH).

  • Exploratory outcomes: glycemic control [ Time Frame: 6-18 months ] [ Designated as safety issue: Yes ]
    within and between treatment group comparisons of change from baseline at specified time points in HbA1c, fasting plasma glucose (FPG), fasting plasma insulin, and insulin sensitivity measured by the homeostasis model assessment (HOMA-s).

  • Exploratory and safety outcomes [ Time Frame: 6-18 months ] [ Designated as safety issue: Yes ]
    Safety endpoints were adverse events (AEs), clinical laboratory assessments, vital signs, and electrocardiograms


Estimated Enrollment: 440
Study Start Date: January 2009
Study Completion Date: January 2014
Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Experimental: 1
Pioglitazone given 30mg/once daily for 12 months.
Drug: Pioglitazone
30 mg/daily for 12 months
Other Name: Actos
Active Comparator: Active comparator: 2
Metformin given 850 mg/twice daily for 12 months.
Drug: Metformin
850 mg/daily for 12 months
Other Name: Glucophage

Detailed Description:

Women with T2DM exhibit normal or higher bone mineral density (BMD) for their age, but with approximately twice the overall risk of bone fragility compared with nondiabetic subjects. Known the apparent association between T2DM and the risk of bone fragility, examining the effects of commonly used oral antidiabetic agents; such as MET and thiazolidinediones (TZDs; for example rosiglitazone [ROS] or PIO), on BMD and/or bone turnover is of great clinical relevance for both diabetic patients and their treating physicians. Recent clinical trials, showed that women treated with ROS had higher risk of bone fragility and self-reported adverse events. Similarly, women on long-term treatment with PIO for T2DM experienced higher incidence of distal extremity fractures. TZDs are agonists of the nuclear transcription factor peroxisome proliferator- activated receptor-γ (PPAR-γ) which increase insulin sensitivity and improve glycemic control in T2DM. PPAR (γ) acts also as a molecular factor that favours adipogenesis over osteoblastogenesis of mesenchymal stem cells. The latter was suggested as a potential mechanism for the effects of TZDs on bone among others. In humans, TZDs decrease BMD and increase bone fragility risk. This study tests whether pioglitazone as compared to MET (both are commonly used in the treatment of T2DM in Saudi Arabia and other countries) affects bone health including bone mineral density, bone turnover markers, and osteocyte biomarker in patients with T2DM.

  Eligibility

Ages Eligible for Study:   50 Years to 65 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • BMD T-score greater than -2.5 at the total hip, femoral neck, and lumbar spine;
  • No prior antidiabetic therapy;
  • Drug-naïve with glycosylated hemoglobin A1c (HbA1c) ≥ 7.0 to ≤ 10.0%. 53.2 mmol/mol to 88.2 mmol/mol);
  • Body-mass index of 40 Kg/m2 and less;
  • Stable body weight for at least 4 months.

Exclusion Criteria:

  • Type 1 diabetes mellitus (presence of GAD auto antibodies);
  • History of diabetes or uncontrolled hypertension;
  • Treatment with antidiabetic agents including TZDs;
  • Chronic diseases known to affect bone;
  • Previous treatment with estrogens and other medications known to affect bone ;
  • Creatinine clearance less than 60 ml/min
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01935804

Locations
Saudi Arabia
Center of Excellence for Osteoporosis Research, King Abdulaziz University
Jeddah, Makkah, Saudi Arabia, 21589
Sponsors and Collaborators
King Abdulaziz University
Investigators
Principal Investigator: Mohammed-Salleh M Ardawi, PhD, FRCPath Center of Excellence for Osteoporosis Research and Faculty of Medicine, King Abdulaziz University
Study Director: Abdulrahim A Rouzi, FRCPC Center of Excellence for Osteoporosis Research, and Faculty of Medicine, King Abdulaziz University
  More Information

No publications provided

Responsible Party: Mohammed-Salleh M. Ardawi, Professor, King Abdulaziz University
ClinicalTrials.gov Identifier: NCT01935804     History of Changes
Other Study ID Numbers: CEOR-01-08
Study First Received: August 27, 2013
Last Updated: June 16, 2014
Health Authority: Saudi Arabia: Ministry for Higher Education

Keywords provided by King Abdulaziz University:
pioglitazone
metformin
hyperglycemic agents
physiological effects of drugs
bone health

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Metabolic Diseases
Glucose Metabolism Disorders
Endocrine System Diseases
Pioglitazone
Metformin
Physiological Effects of Drugs
Hypoglycemic Agents
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 29, 2014