Effect of Exenatide, Sitagliptin or Glimepiride on Functional ß -Cell Mass

NCT00775684 | Completed Results

• 1 other identifier: 808425
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 3

Brief Summary

This study evaluates exenatide, sitagliptin, and glimepiride for the treatment of high blood sugar in patients with impaired fasting glucose or early type 2 diabetes. The purpose of this study is to determine if exenatide and sitagliptin increase the amount of insulin made by the pancreas compared to glimepiride. It is hypothesized that exenatide or sitagliptin will sustain or increase the amount of insulin made by the pancreas in comparison to glimepiride.

Conditions

Pre-diabetes; Type 2 Diabetes

Keywords

Exenatide; Sitagliptin; Glimepiride; Glucagon-Like Peptide-1; Impaired Fasting Glucose; Type 2 Diabetes; Beta-cell Function; Beta-cell Secretory Capacity; Glucose-potentiated arginine

Outcome Measures

Primary Outcomes (2)

• Effect on Functional Beta-cell Mass as Determined by Change in ß-cell Secretory Capacity at 6 Months (μU/ml)

  The acute insulin response to arginine (AIRarg) performed during the 340mg/dl glucose clamp allows for estimation of the the beta-cell secretory capacity (AIRmax) or functional beta-cell mass. Changes from baseline to 6 months of AIRmax were compared across groups

  Baseline and 6 months

• Effect on Functional Beta-cell Mass as Determined by Change in ß-cell Secretory Capacity at 6 Months (pg/mL)

  AGRmin is performed during the 340mg/dl glucose clamp allows for estimation of the minimum alpha-cell glucagon secretion. Changes from baseline to 6 months of AGRmin were compared across groups.

  Baseline and 6 months

Secondary Outcomes (3)

• Change in Acute Insulin Response to Arginine. (AIRarg)

  Baseline and 6 months

• Insulin Sensitivity at Baseline and 6 Months

  Baseline and 6 months

• PG 50 (the Plasma Glucose Level at Which Half-maximal Insulin Secretion is Achieved During the Glucose-potentiated Arginine Test) at Baseline and 6 Months

  Baseline and 6 months

Study Arms (3)

Exenatide

EXPERIMENTAL

Exenatide (Byetta®)-5 µg injected subcutaneously twice daily and increased after 1 month to 10 µg twice daily as tolerated by gastrointestinal effects

Drug: Exenatide

Sitagliptin

EXPERIMENTAL

Sitagliptin (Januvia®)-100 mg by mouth every morning

Drug: Sitagliptin

Glimepiride

ACTIVE COMPARATOR

Glimepiride (Amaryl®)-0.5 mg by mouth every morning and then increased by 0.5 - 1.0 mg at each monthly visit to achieve an average fasting glucose \< 110mg/dl

Drug: Glimepiride

Interventions

Exenatide DRUG

Exenatide (Byetta®)-5 µg injected subcutaneously twice daily and increased after 1 month to 10 µg twice daily as tolerated by gastrointestinal effects

Also known as: Byetta®

Exenatide

Sitagliptin DRUG

Sitagliptin (Januvia®)100 mg by mouth every morning

Also known as: Januvia®

Sitagliptin

Glimepiride DRUG

Glimepiride (Amaryl®)-0.5 mg by mouth every morning and then increased by 0.5 - 1.0 mg at each monthly visit to achieve an average fasting glucose \< 110mg/dl

Also known as: Amaryl®

Glimepiride

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female patients age 18 to 70 years.
• Ability to provide written informed consent
• Mentally stable and able to comply with the procedures of the study protocol
• Clinical history compatible with impaired fasting glucose or early T2D as defined by a plasma glucose concentration between 110-159 mg/dl following a 12 hour overnight fast performed off any anti-diabetogenic agent for at least 2 weeks (6 weeks for thiazolidinediones)
• Stable body weight (+ 5%) for at least 2 weeks
• Female Patients: Agree to use adequate contraception if reproductively capable. Adequate contraception includes either a hormonal or barrier method, or surgical sterilization.

You may not qualify if:

• Diagnosis of type 1 diabetes
• Receiving insulin, exenatide (Byetta®), or sitagliptin (Januvia®) treatment or taking \> 2 oral anti-diabetogenic agents for the treatment of diabetes
• BMI \> 44 kg/m2
• Allergy to any sulfa-containing compounds
• Uncontrolled hypertension (Systolic Blood Pressure \>160 or Diastolic Blood Pressure \> 100 mmHg)
• Uncontrolled hyperlipidemia (triglycerides \> 500 or LDL \> 160 mg/dl)
• Elevation of liver function tests \> 2 times the upper limit of normal
• Estimated Glomerular Filtration Rate (GFR) \< 55 ml/min/1.73m2 (46)
• Hyperkalemia (serum potassium \> 5.5 mmol/L)
• Moderate anemia (hemoglobin concentration \< 12 g/dl in men and \< 11 g/dl in women)
• Female patients: pregnant or lactating
• Hepatic cirrhosis
• Known active alcohol or substance abuse
• Active cardiovascular disease
• Use of any investigational agent within 6 weeks of the baseline visit

Sponsors & Collaborators

• University of Pennsylvania: lead
• Pennsylvania Department of Health: collaborator

Study Sites (3)

Clinical and Translational Research Center, Hospital of University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Rodebaugh Diabetes Center, Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Pennsylvania Hospital

Philadelphia, Pennsylvania, 19107, United States

Location

Related Publications (8)

• National Diabetes Statistics http://diabetes.niddk.nih.gov/dm/pubs/statistics/index.htm 2005. 2-16-2007 Ref Type: Electronic Citation

  BACKGROUND

• King H, Aubert RE, Herman WH. Global burden of diabetes, 1995-2025: prevalence, numerical estimates, and projections. Diabetes Care. 1998 Sep;21(9):1414-31. doi: 10.2337/diacare.21.9.1414.

  PMID: 9727886 BACKGROUND

• U.K. prospective diabetes study 16. Overview of 6 years' therapy of type II diabetes: a progressive disease. U.K. Prospective Diabetes Study Group. Diabetes. 1995 Nov;44(11):1249-58.

  PMID: 7589820 BACKGROUND

• Butler AE, Janson J, Bonner-Weir S, Ritzel R, Rizza RA, Butler PC. Beta-cell deficit and increased beta-cell apoptosis in humans with type 2 diabetes. Diabetes. 2003 Jan;52(1):102-10. doi: 10.2337/diabetes.52.1.102.

  PMID: 12502499 BACKGROUND

• Ritzel RA, Butler AE, Rizza RA, Veldhuis JD, Butler PC. Relationship between beta-cell mass and fasting blood glucose concentration in humans. Diabetes Care. 2006 Mar;29(3):717-8. doi: 10.2337/diacare.29.03.06.dc05-1538. No abstract available.

  PMID: 16505537 BACKGROUND

• Kahn SE. Clinical review 135: The importance of beta-cell failure in the development and progression of type 2 diabetes. J Clin Endocrinol Metab. 2001 Sep;86(9):4047-58. doi: 10.1210/jcem.86.9.7713. No abstract available.

  PMID: 11549624 BACKGROUND

• Godsland IF, Jeffs JAR, Johnston DG. Loss of beta cell function as fasting glucose increases in the non-diabetic range. Diabetologia. 2004 Jul;47(7):1157-1166. doi: 10.1007/s00125-004-1454-z. Epub 2004 Jul 13.

  PMID: 15249997 BACKGROUND

• Ward WK, Bolgiano DC, McKnight B, Halter JB, Porte D Jr. Diminished B cell secretory capacity in patients with noninsulin-dependent diabetes mellitus. J Clin Invest. 1984 Oct;74(4):1318-28. doi: 10.1172/JCI111542.

  PMID: 6384269 BACKGROUND

Related Links

• Michael R. Rickels, M.D., M.S. Faculty Bio
• Rodebaugh Diabetes Center
• Center for Human Phenomic Science (Formerly the Clinical and Translational Research Center)
• Institute for Diabetes, Obesity \& Metabolism - Clinical Trials

MeSH Terms

Conditions

Glucose Intolerance; Diabetes Mellitus, Type 2

Interventions

Exenatide; Sitagliptin Phosphate; glimepiride

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Peptides; Amino Acids, Peptides, and Proteins; Venoms; Complex Mixtures; Toxins, Biological; Biological Factors; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrazines

Results Point of Contact

• Title: Professor of Medicine, Director of Translational Research Program
• Organization: University of Pennsylvania

rickels@pennmedicine.upenn.edu

215 746-0025

Study Officials

• Michael Rickels, M.D., M.S.

  University of Pennsylvania, Division of Endocrinology, Diabetes & Metabolism

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: October 17, 2008
• First Posted: October 20, 2008
• Study Start: October 1, 2008
• Primary Completion: November 1, 2012
• Study Completion: November 1, 2012
• Last Updated: June 7, 2022
• Results First Posted: December 6, 2017

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)