Glycemic Control and Complications in Diabetes Mellitus Type 2 (VADT)

NCT00032487 | Completed Phase 3 Results DMC

• 1 other identifier: 465
• Study Type: interventional
• Target: 1,791
• Locations: 2 countries
• Sites: 21

Brief Summary

This study is a prospective, 2-arm, randomized controlled trial to determine whether glycemic control, achieved through intensification of treatment, is effective in preventing clinical macrovascular complications in patients with type 2 DM who are no longer responsive to oral agents alone. The study consists of a two-year accrual period and five years of follow-up (7 years total) of 1700 patients across 20 centers. We have powered the study to detect a 21% reduction in the primary event rate. Additional study goals are to determine whether the expenditures, discomfort, and adverse effects associated with intensive intervention are justified in terms of their clinical benefits, considering both macrovascular and microvascular complications.

Conditions

Type 2 Diabetes Mellitus

Keywords

DM; glycemic control; insulin; type 2 diabetes mellitus

Outcome Measures

Primary Outcomes (1)

• Primary Major Macrovascular Events

  Myocardial infarction (MI), intervention for coronary artery or Peripheral Vascular Disease (PVD), severe inoperable Coronary Artery Disease (CAD), new or worsening Congestive Heart Failure (CHF), stroke, Cardiovascular (CV) death, or amputation for ischemic gangrene.

  Post baseline time to the first major macrovascular event up to 82 months

Secondary Outcomes (1)

• Secondary Endpoint

  Post baseline time to first event up to 82 months

Study Arms (2)

Standard glycemic control

ACTIVE COMPARATOR

Standard glycemic control to maintain HbA1c between 8.0-9.0%. Metformin 500 mg Rosiglitazone 4 mg Glimepiride 2 mg Insulin 1 unit 9 lbs

Drug: Insulin; Drug: Glimepiride; Drug: Rosiglitazone; Drug: Metformin

Intensive glycemic control

EXPERIMENTAL

Intensive glycemic control lower HbA1c below 6.0%. Metformin 500 mg (go up to 2000 mg) Rosiglitazone 4 mg bid Glimepiride 8 mg Insulin 1 unit 9 lbs add one injection to Arm 1

Drug: Insulin; Drug: Glimepiride; Drug: Rosiglitazone; Drug: Metformin

Interventions

Insulin DRUG

Insulin (intermediate or long-lasting) in a.m. 1 unit 9 lbs Arm 1 Insulin (intermediate or long-lasting) in a.m. 1 unit 9 lbs, add one injection of insulin Arm 2

Also known as: Lente

Intensive glycemic control; Standard glycemic control

Glimepiride DRUG

Glimepiride 2 mg Arm 1 Glimepiride 8 mg Arm 2

Also known as: Amaryl

Intensive glycemic control; Standard glycemic control

Rosiglitazone DRUG

Rosiglitazone 4 mg Arm 1 Rosiglitazone 4 mg bid Arm 2

Also known as: Avandia

Intensive glycemic control; Standard glycemic control

Metformin DRUG

Metformin 500 mg (go up to 1000 mg) Arm 1 Metformin 500 mg (go up to 2000 mg) Arm

Also known as: Glumetza

Intensive glycemic control; Standard glycemic control

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with type 2 DM who are no longer responsive to maximum dose of one or more oral agents.

You may not qualify if:

• Angina pectoris, Canadian Class I-II,
• congestive heart failure, Class III-IV,
• stroke, incapacitating or in last 6 months,
• Myocardial infarction (MI) or invasive cardiovascular procedure within the past six months,
• ongoing diabetic gangrene,
• BMI \> 40,
• hemoglobinopathy that interferes with A1c monitoring,
• serum creatinine \> 1.6 mg/dL,
• fasting C-peptide \< 0.21 pmol/ml,
• Alanine Amino Transaminase (ALT) \> 3 times normal or serum bilirubin \> 1.9 mg/dL,
• malignancy or noncardiac life-threatening diseases making life expectancy \< 5 years,
• autonomic neuropathy,
• symptomatic pancreatic insufficiency (endocrine or exocrine),
• recurrent seizures within the past year,
• hypopituitarism,

Sponsors & Collaborators

• VA Office of Research and Development: lead
• National Eye Institute (NEI): collaborator
• SmithKline Beecham: collaborator

Study Sites (21)

Carl T. Hayden VA Medical Center

Phoenix, Arizona, 85012, United States

Location

Southern Arizona VA Health Care System, Tucson

Tucson, Arizona, 85723, United States

Location

VA Central California Health Care System, Fresno

Fresno, California, 93703, United States

Location

VA Medical Center, Long Beach

Long Beach, California, 90822, United States

Location

VA San Diego Healthcare System, San Diego

San Diego, California, 92161, United States

Location

Miami VA Healthcare System, Miami, FL

Miami, Florida, 33125, United States

Location

Edward Hines, Jr. VA Hospital

Hines, Illinois, 60141-5000, United States

Location

Richard Roudebush VA Medical Center, Indianapolis

Indianapolis, Indiana, 46202-2884, United States

Location

VA Medical Center, Lexington

Lexington, Kentucky, 40502, United States

Location

VA Medical Center, Minneapolis

Minneapolis, Minnesota, 55417, United States

Location

VA Medical Center, Omaha

Omaha, Nebraska, 68105-1873, United States

Location

VA New Jersey Health Care System, East Orange

East Orange, New Jersey, 07018, United States

Location

VA Pittsburgh Health Care System

Pittsburgh, Pennsylvania, 15240, United States

Location

Ralph H Johnson VA Medical Center, Charleston

Charleston, South Carolina, 29401-5799, United States

Location

VA Medical Center

Nashville, Tennessee, 37212-2637, United States

Location

Michael E. DeBakey VA Medical Center (152)

Houston, Texas, 77030, United States

Location

VA South Texas Health Care System, San Antonio

San Antonio, Texas, 78229, United States

Location

Hunter Holmes McGuire VA Medical Center

Richmond, Virginia, 23249, United States

Location

VA Medical Center, Salem VA

Salem, Virginia, 24153, United States

Location

VA Puget Sound Health Care System, Seattle

Seattle, Washington, 98108, United States

Location

VA Medical Center, San Juan

San Juan, 00921, Puerto Rico

Location

Related Publications (25)

• Duckworth W, Abraira C, Moritz T, Reda D, Emanuele N, Reaven PD, Zieve FJ, Marks J, Davis SN, Hayward R, Warren SR, Goldman S, McCarren M, Vitek ME, Henderson WG, Huang GD; VADT Investigators. Glucose control and vascular complications in veterans with type 2 diabetes. N Engl J Med. 2009 Jan 8;360(2):129-39. doi: 10.1056/NEJMoa0808431. Epub 2008 Dec 17.

  PMID: 19092145 RESULT

• Moritz T, Duckworth W, Abraira C. Veterans Affairs diabetes trial--corrections. N Engl J Med. 2009 Sep 3;361(10):1024-5. doi: 10.1056/NEJMc096250. No abstract available.

  PMID: 19726779 RESULT

• Emanuele N, Moritz T, Klein R, Davis MD, Glander K, Khanna A, Thottapurathu L, Bahn G, Duckworth W, Abraira C; Veterans Affairs Diabetes Trial Study Group. Ethnicity, race, and clinically significant macular edema in the Veterans Affairs Diabetes Trial (VADT). Diabetes Res Clin Pract. 2009 Nov;86(2):104-10. doi: 10.1016/j.diabres.2009.08.001. Epub 2009 Aug 31.

  PMID: 19720420 RESULT

• Control Group; Turnbull FM, Abraira C, Anderson RJ, Byington RP, Chalmers JP, Duckworth WC, Evans GW, Gerstein HC, Holman RR, Moritz TE, Neal BC, Ninomiya T, Patel AA, Paul SK, Travert F, Woodward M. Intensive glucose control and macrovascular outcomes in type 2 diabetes. Diabetologia. 2009 Nov;52(11):2288-98. doi: 10.1007/s00125-009-1470-0. Epub 2009 Aug 5.

  PMID: 19655124 RESULT

• Abraira C, Duckworth WC, Moritz T; VADT Group. Glycaemic separation and risk factor control in the Veterans Affairs Diabetes Trial: an interim report. Diabetes Obes Metab. 2009 Feb;11(2):150-6. doi: 10.1111/j.1463-1326.2008.00933.x. Epub 2008 Jul 29.

  PMID: 18671796 RESULT

• Emanuele N, Klein R, Moritz T, Davis MD, Glander K, Anderson R, Reda D, Duckworth W, Abraira C; VADT Study Group. Comparison of dilated fundus examinations with seven-field stereo fundus photographs in the Veterans Affairs Diabetes Trial. J Diabetes Complications. 2009 Sep-Oct;23(5):323-9. doi: 10.1016/j.jdiacomp.2008.02.010. Epub 2008 Apr 11.

  PMID: 18406632 RESULT

• Meyers CD, McCarren M, Wong ND, Abraira C, Duckworth WC, Kashyap ML; VADT Investigators. Baseline achievement of lipid goals and usage of lipid medications in patients with diabetes mellitus (from the Veterans Affairs Diabetes Trial). Am J Cardiol. 2006 Jul 1;98(1):63-5. doi: 10.1016/j.amjcard.2006.01.061. Epub 2006 May 4.

  PMID: 16784922 RESULT

• Duckworth WC, McCarren M, Abraira C; VADT Investigators. Control of cardiovascular risk factors in the Veterans Affairs Diabetes Trial in advanced type 2 diabetes. Endocr Pract. 2006 Jan-Feb;12 Suppl 1:85-8. doi: 10.4158/EP.12.S1.85.

  PMID: 16627388 RESULT

• Kirkman MS, McCarren M, Shah J, Duckworth W, Abraira C; VADT Study Group. The association between metabolic control and prevalent macrovascular disease in Type 2 diabetes: the VA Cooperative Study in diabetes. J Diabetes Complications. 2006 Mar-Apr;20(2):75-80. doi: 10.1016/j.jdiacomp.2005.06.013.

  PMID: 16504835 RESULT

• Emanuele N, Sacks J, Klein R, Reda D, Anderson R, Duckworth W, Abraira C; Veterans Affairs Diabetes Trial Group. Ethnicity, race, and baseline retinopathy correlates in the veterans affairs diabetes trial. Diabetes Care. 2005 Aug;28(8):1954-8. doi: 10.2337/diacare.28.8.1954.

  PMID: 16043738 RESULT

• Abraira C, Duckworth W, McCarren M, Emanuele N, Arca D, Reda D, Henderson W; VA Cooperative Study of Glycemic Control and Complications in Diabetes Mellitus Type 2. Design of the cooperative study on glycemic control and complications in diabetes mellitus type 2: Veterans Affairs Diabetes Trial. J Diabetes Complications. 2003 Nov-Dec;17(6):314-22. doi: 10.1016/s1056-8727(02)00277-5.

  PMID: 14583175 RESULT

• Duckworth WC, McCarren M, Abraira C; VA Diabetes Trial. Glucose control and cardiovascular complications: the VA Diabetes Trial. Diabetes Care. 2001 May;24(5):942-5. doi: 10.2337/diacare.24.5.942. No abstract available.

  PMID: 11347758 RESULT

• Anderson RJ, Bahn GD, Moritz TE, Kaufman D, Abraira C, Duckworth W; VADT Study Group. Blood pressure and cardiovascular disease risk in the Veterans Affairs Diabetes Trial. Diabetes Care. 2011 Jan;34(1):34-8. doi: 10.2337/dc10-1420. Epub 2010 Nov 8.

  PMID: 21059830 RESULT

• Agrawal L, Azad N, Emanuele NV, Bahn GD, Kaufman DG, Moritz TE, Duckworth WC, Abraira C; Veterans Affairs Diabetes Trial (VADT) Study Group. Observation on renal outcomes in the Veterans Affairs Diabetes Trial. Diabetes Care. 2011 Sep;34(9):2090-4. doi: 10.2337/dc11-0175. Epub 2011 Jul 20.

  PMID: 21775749 RESULT

• Zhou JJ, Koska J, Bahn G, Reaven P. Fasting Glucose Variation Predicts Microvascular Risk in ACCORD and VADT. J Clin Endocrinol Metab. 2021 Mar 25;106(4):1150-1162. doi: 10.1210/clinem/dgaa941.

  PMID: 33367811 DERIVED

• Reaven PD, Emanuele NV, Wiitala WL, Bahn GD, Reda DJ, McCarren M, Duckworth WC, Hayward RA; VADT Investigators. Intensive Glucose Control in Patients with Type 2 Diabetes - 15-Year Follow-up. N Engl J Med. 2019 Jun 6;380(23):2215-2224. doi: 10.1056/NEJMoa1806802.

  PMID: 31167051 DERIVED

• Davis SN, Duckworth W, Emanuele N, Hayward RA, Wiitala WL, Thottapurathu L, Reda DJ, Reaven PD; Investigators of the Veterans Affairs Diabetes Trial. Effects of Severe Hypoglycemia on Cardiovascular Outcomes and Death in the Veterans Affairs Diabetes Trial. Diabetes Care. 2019 Jan;42(1):157-163. doi: 10.2337/dc18-1144. Epub 2018 Nov 19.

  PMID: 30455335 DERIVED

• Azad N, Bahn GD, Emanuele NV, Agrawal L, Ge L, Reda D, Klein R, Reaven PD, Hayward R; VADT Study Group. Association of Blood Glucose Control and Lipids With Diabetic Retinopathy in the Veterans Affairs Diabetes Trial (VADT). Diabetes Care. 2016 May;39(5):816-22. doi: 10.2337/dc15-1897. Epub 2016 Mar 22.

  PMID: 27006510 DERIVED

• Saremi A, Bahn GD, Reaven PD; Veterans Affairs Diabetes Trial (VADT). A Link Between Hypoglycemia and Progression of Atherosclerosis in the Veterans Affairs Diabetes Trial (VADT). Diabetes Care. 2016 Mar;39(3):448-54. doi: 10.2337/dc15-2107. Epub 2016 Jan 19.

  PMID: 26786575 DERIVED

• Hayward RA, Reaven PD, Wiitala WL, Bahn GD, Reda DJ, Ge L, McCarren M, Duckworth WC, Emanuele NV; VADT Investigators. Follow-up of glycemic control and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2015 Jun 4;372(23):2197-206. doi: 10.1056/NEJMoa1414266.

  PMID: 26039600 DERIVED

• Saremi A, Schwenke DC, Bahn G, Ge L, Emanuele N, Reaven PD; VADT Investigators. The effect of intensive glucose lowering therapy among major racial/ethnic groups in the Veterans Affairs Diabetes Trial. Metabolism. 2015 Feb;64(2):218-25. doi: 10.1016/j.metabol.2014.10.010. Epub 2014 Oct 17.

  PMID: 25456099 DERIVED

• Anderson RJ, Bahn GD, Emanuele NV, Marks JB, Duckworth WC; VADT Study Group. Blood pressure and pulse pressure effects on renal outcomes in the Veterans Affairs Diabetes Trial (VADT). Diabetes Care. 2014 Oct;37(10):2782-8. doi: 10.2337/dc14-0284. Epub 2014 Jul 21.

  PMID: 25048382 DERIVED

• Koska J, Saremi A, Bahn G, Yamashita S, Reaven PD; Veterans Affairs Diabetes Trial Investigators. The effect of intensive glucose lowering on lipoprotein particle profiles and inflammatory markers in the Veterans Affairs Diabetes Trial (VADT). Diabetes Care. 2013 Aug;36(8):2408-14. doi: 10.2337/dc12-2082. Epub 2013 Mar 27.

  PMID: 23536583 DERIVED

• Saremi A, Moritz TE, Anderson RJ, Abraira C, Duckworth WC, Reaven PD; Veterans Affairs Diabetes Trial (VADT). Rates and determinants of coronary and abdominal aortic artery calcium progression in the Veterans Affairs Diabetes Trial (VADT). Diabetes Care. 2010 Dec;33(12):2642-7. doi: 10.2337/dc10-1388. Epub 2010 Aug 31.

  PMID: 20807873 DERIVED

• Meier M, Hummel M. Cardiovascular disease and intensive glucose control in type 2 diabetes mellitus: moving practice toward evidence-based strategies. Vasc Health Risk Manag. 2009;5:859-71. doi: 10.2147/vhrm.s4808. Epub 2009 Nov 2.

  PMID: 19898642 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Insulin Resistance

Interventions

Insulin; glimepiride; Rosiglitazone; Metformin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Hyperinsulinism

Intervention Hierarchy (Ancestors)

Proinsulin; Insulins; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins; Thiazolidinediones; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Biguanides; Guanidines; Amidines

Limitations and Caveats

Our study had several limitations. Since we were studying veterans, the patients were predominantly men, and extrapolation of our findings to women must be done with caution.Changes in therapeutic agents have occurred since the design of our protocol

Results Point of Contact

• Title: Project Manager
• Organization: Hines CSPCC

tamara.paine@va.gov

708-202-5785

Study Officials

• Carlos Abraira, MD

  Miami VA Healthcare System, Miami, FL

  STUDY CHAIR

• William Duckworth, MD

  Phoenix VA Health Care System, Phoenix, AZ

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 21, 2002
• First Posted: March 22, 2002
• Study Start: December 1, 2000
• Primary Completion: May 30, 2008
• Study Completion: May 30, 2008
• Last Updated: March 30, 2017
• Results First Posted: February 12, 2014

Record last verified: 2017-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (20); PR (1)