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Safety and Efficacy Study to Compare Vildagliptin to Pioglitazone as Adding on Metformin in Type 2 Diabetes

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ClinicalTrials.gov Identifier: NCT01882907
Recruitment Status : Completed
First Posted : June 21, 2013
Results First Posted : March 17, 2015
Last Update Posted : December 29, 2017
Sponsor:
Information provided by (Responsible Party):
Pusan National University Hospital

Brief Summary:
The purpose of this study is to compare the effect of 16 weeks treatment with vildagliptin to pioglitazone as add-on the therapy to metformin in patients with type 2 diabetes inadequately controlled with metformin monotherapy.

Condition or disease Intervention/treatment Phase
Type 2 Diabetes Drug: vildagliptin Drug: Pioglitazone Phase 4

Detailed Description:

Type 2 diabetes mellitus (T2DM) is a chronic progressive disease characterized by hyperglycemia that result from pancreatic islet dysfunction. Presently available oral antihypoglycemic drug improves glycemic control over the short term, none has been shown to stop the progressive decline in beta cell function which contributes to the deterioration of glycemic control over time.

Pathophysiology of T2DM is known as tissue resistance for insulin and progressive beta cell failure. Which one attributes first is unclear, but non-obese T2DM patients often show normal fasting plasma glucose (FPG) but postprandial plasma glucose (PPG) level is high and reduced or lacking normal compensatory insulin secretion. In Korea, more than 80% of T2DM are non-obese type (BMI >= 27 ) and it was observed that basal insulin level and compensatory insulin secretion reaction were reduced in normal healthy population. Based on that, metformin is an established first line treatment for type 2 diabetes, acting primarily to enhance hepatic and peripheral insulin sensitivity. However, it has become increasingly apparent that many patients require a combination of agents to attain optimal glycemic control.

Better understanding of incretin effect on the pathophysiology of T2DM has recently led to development of new oral hypoglycemic agents. Vildagliptin is a potent and highly selective dipeptidyl peptidase (DPP)-IV inhibitor that improves islet function by increasing pancreatic alpha and beta cell responsiveness to glucose. Studies in patients with T2DM have shown that vildagliptin significantly reduced HbA1c and FPG level from baseline and did not induce weight gain and the incidence of hypoglycemia was low. In addition, studies in rodents support an effort of vildagliptin on beta cell remodeling.

The thiazolidinediones are effective in reducing HbA1C in obese T2DM patients and it is known that only thiazolidinedione can delay the beta cell failure . But recently, thiazolidinediones were found to be associated with a decrease in bone mineral density and to raise the risk of myocardial infarct and cardiovascular related mortality. Thus, there is a need for new classes of blood glucose lowering drug which has the potential to delay or prevent the progression of T2DM.


Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 293 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-label, Randomized, Active-controlled Study to Compare the Effect of 16 Weeks Treatment With Vildagliptin to Pioglitazone as add-on Therapy to Metformin in Type 2 Diabetic Patients Inadequately Controlled With Metformin Monotherapy
Study Start Date : December 2009
Actual Primary Completion Date : March 2013
Actual Study Completion Date : March 2013

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: vildagliptin
vildagliptin add-on the therapy to metformin in patients with type 2 diabetes inadequately controlled with metformin monotherapy
Drug: vildagliptin
vildagliptin 50mg bid for 16 weeks
Other Name: Galvus

Active Comparator: pioglitazone
Pioglitazone add-on the therapy to metformin in patients with type 2 diabetes inadequately controlled with metformin monotherapy
Drug: Pioglitazone
Pioglitazone 15mg bid for 16 weeks
Other Name: Actos




Primary Outcome Measures :
  1. Non-inferiority of HbA1C Change From Baseline in Vildagliptin + Metformin Group Compared With Pioglitazone + Metformin Group [ Time Frame: 16 weeks ]

Secondary Outcome Measures :
  1. To Compare Changes of FPG and PPG From Baseline Between Vildagliptin + Metformin and Pioglitazone + Metformin Groups [ Time Frame: 16 weeks , visit 5 ]
  2. To Compare Changes of Lipid Profiles From Baseline Between Vildagliptin + Metformin and Pioglitazone + Metformin Groups [ Time Frame: 16 weeks, visit 5 ]
  3. To Compare Changes of Body Weight From Baseline Between Vildagliptin + Metformin and Pioglitazone + Metformin Groups [ Time Frame: 16 weeks, visit 5 ]
  4. To Compare Numbers of Participants With Adverse Events Between Vildagliptin + Metformin and Pioglitazone + Metformin Groups [ Time Frame: 16 weeks, visit 3,4,5 ]

    Safety assessments

    - hypoglycemia, other side effects, Laboratory data, Physical examination, Vital sign with blood pressure and pulse rate, Electrocardiography



Other Outcome Measures:
  1. To Compare Changes of Insulin and C-peptide From Baseline Between Vildagliptin + Metformin and Pioglitazone + Metformin Groups [ Time Frame: 16 weeks, visit 5 ]
  2. To Compare Changes of Homeostasis Model Assessment-insulin Resistance and Beta From Baseline Between Vildagliptin + Metformin and Pioglitazone + Metformin Groups [ Time Frame: 16 weeks, visit 5 ]
  3. To Compare Changes of Adipocytokine From Baseline Between Vildagliptin + Metformin and Pioglitazone + Metformin Groups [ Time Frame: 16 weeks, visit 5 ]


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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
Criteria

Inclusion Criteria:

  1. Age in the range of 18 to 80 years
  2. HbA1c 7 to 11%
  3. FPG < 270 mg/dL (15 mmol/L);
  4. Agreement to maintain prior diet & exercise
  5. Written informed consent to participate in the study

Exclusion criteria:

  1. Type 1 diabetes or Any kind of secondary diabetes
  2. Pregnant or lactating women
  3. Acute infections which may affect blood glucose control within 4 weeks prior to visit 1.
  4. Significant diabetes complications e.g., symptomatic autonomic neuropathy or gastroparesis
  5. Previous history of severe cardiovascular disease such as

    1. Torsades de Pointes, sustained and clinically relevant ventricular tachycardia, or ventricular fibrillation
    2. Percutaneous coronary intervention within the past 3 months
  6. Any of the following within the past 6 months

    1. Myocardial infarction (MI) (if the visit 1 ECG reveals patterns consistent with an MI and the date of the event cannot be determined, then the patient can enter the study at the discretion of the investigator and the sponsor)
    2. Coronary artery bypass surgery
    3. Unstable angina
    4. Stroke
  7. Congestive heart failure (NYHA class I to IV)
  8. Liver disease such as cirrhosis or chronic active hepatitis
  9. Known sensitivity to pioglitazone, rosiglitazone, or similar drugs
  10. Chronic insulin treatment (> 4 weeks of treatment in the absence of an intercurrent illness) within the past 6 months
  11. Chronic oral or parenteral corticosteroid treatment (> 7 consecutive days of treatment) within 8 weeks prior to visit 1
  12. Any of the following laboratory abnormalities

    1. Alanine aminotransferase (ALT), aspartate aminotransferase (AST) greater than 2.5 times the upper limit of the normal range at visit 1
    2. Direct bilirubin greater than 1.3 times the upper limit of the normal range at visit 1
    3. Serum creatinine levels > 2.5 mg/dL (220 μmol/L) at visit 1
    4. Clinically significant thyroid-stimulating hormone (TSH) outside normal range at visit 1

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 ClinicalTrials.gov identifier (NCT number): NCT01882907


Locations
Korea, Republic of
Busan Saint Mary's Medical Center
Busan, Korea, Republic of
Dong-AUniversity Medical Center
Busan, Korea, Republic of
Inje University Baik Hospital
Busan, Korea, Republic of
Kosin University Hospital
Busan, Korea, Republic of
Pusan National University Hospital
Busan, Korea, Republic of
Changwon Fatima Hospital
Changwon, Korea, Republic of
Daegu Catholic University Medical Center
Daegu, Korea, Republic of
Keimyung University Dongsan Medical Center
Daegu, Korea, Republic of
Kyungbuk National Universtiy Hospital
Daegu, Korea, Republic of
Chonnam National University Hospital
Gwangju, Korea, Republic of
Chosun University Hospital
Gwangju, Korea, Republic of
Chonbuk National University Hospital
Jeonju, Korea, Republic of
Gyeongsang National University Hospital
Jinju, Korea, Republic of
Masan Samsung Medical Center
Masan, Korea, Republic of
Ulsan University Hospital
Ulsan, Korea, Republic of
Sponsors and Collaborators
Pusan National University Hospital
Investigators
Principal Investigator: In Ju Kim, MD Pusan National University Hospital

Responsible Party: Pusan National University Hospital
ClinicalTrials.gov Identifier: NCT01882907     History of Changes
Other Study ID Numbers: CLAF237AKR05T
First Posted: June 21, 2013    Key Record Dates
Results First Posted: March 17, 2015
Last Update Posted: December 29, 2017
Last Verified: December 2017

Keywords provided by Pusan National University Hospital:
vildagliptin
metformin

Additional relevant MeSH terms:
Diabetes Mellitus, Type 2
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Pioglitazone
Vildagliptin
Metformin
Hypoglycemic Agents
Physiological Effects of Drugs
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action