Effect of Combined Incretin-Based Therapy Plus Canagliflozin on Glycemic Control and the Compensatory Rise in Hepatic Glucose Production in Type 2 Diabetic Patients

NCT02324842 | Completed Results

• 2 other identifiers: 28431754DIA4009HSC20140322H
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

Brief Summary

Specific Aim 1.To examine whether the combination of liraglutide plus canagliflozin can prevent the increase in Hepatic Glucose Production (HGP) following institution of canagliflozin therapy and produce an additive or even synergistic effect to lower the plasma glucose concentration and A1c. Specific Aim 2: To examine whether combination therapy with liraglutide plus canagliflozin can produce an additive, or even synergistic, effect to promote weight loss and reduction in hepatic and visceral fat content. Specific Aim 3. To examine whether combination therapy with liraglutide plus canagliflozin can produce an additive or even synergistic effect to reduce systolic/diastolic blood pressure and 24-hour integrated blood pressure.

Conditions

Type 2 Diabetes Mellitus

Outcome Measures

Primary Outcomes (2)

• HbA1c at 4 Months

  Primary end point of the study is the HbA1c level in response to canagliflozin alone, liraglutide or canagliflozin with liraglutide.

  Approximately 4 months

• Fasting Plasma Glucose (FPG) at 4 Months

  Values will be presented as the mean + (Standard Deviation) SD. The difference in HGP and all secondary endpoints at study end versus baseline will be calculated and compared between each active treatment group with ANOVA.

  Baseline to Approximately 4 months

Secondary Outcomes (1)

• Body Mass Index (BMI) at 4 Months

  Approximately 4 months

Other Outcomes (5)

• Change in Matsuda Index of Insulin Sensitivity, Insulin Secretion, and Beta Cell Function During Oral Glucose Tolerance Test (OGTT)

  Change from Baseline to Approximately 4 months

• Change in Free Plasma Insulin at the End of the Study From Baseline Value

  At Approximately 4 months

• Change in Plasma Glucagon Concentration at the End of the Study Compared to Baseline

  Approximately 4 months

Study Arms (3)

Canagliflozin

ACTIVE COMPARATOR

canagliflozin (film-coated tablet), 100 mg/day, increased to 300 mg/day after week two if tolerated without side effects

Drug: Canagliflozin

liraglutide

ACTIVE COMPARATOR

liraglutide, 1.2 mg/day, increased to 1.8 mg/day after week two if tolerated without side effects

Drug: Liraglutide

canagliflozin plus liraglutide

ACTIVE COMPARATOR

canagliflozin, 100 mg/day, plus liraglutide, 1.2 mg/day, increased to 300 mg/day and 1.8 mg/day, respectively at week two, if tolerated without side effects

Drug: Canagliflozin; Drug: Liraglutide

Interventions

Canagliflozin DRUG

Canagliflozin is a sodium-glucose co-transporter 2 (SGLT2) inhibitor indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus (1)

Also known as: Invokana

Canagliflozin; canagliflozin plus liraglutide

Liraglutide DRUG

Liraglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.

Also known as: Victoza

canagliflozin plus liraglutide; liraglutide

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 subjects between the ages of 18-70
• Subjects with Type 2 Diabetes Mellitus (T2DM)
• Drug naïve or on stable dose (more than 3 months) of metformin with or without sulfonylurea
• Have an HbA1c levels ≥7.0% and \<10.0%
• Stable weight (± 3 lbs) over the preceding 3 months

You may not qualify if:

• Subjects taking drugs known to affect glucose metabolism (other than metformin) will be excluded.
• Individuals with evidence of proliferative diabetic retinopathy or plasma creatinine \>1.4 females or \>1.5 males or estimated Glomerular Filtration Rate (eGFR)\< 60 ml/min.172m2 will be excluded
• Unstable body weight (change of greater than ±3 lbs over the preceding 3 months)
• Participates in excessively heavy exercise program

Sponsors & Collaborators

• The University of Texas Health Science Center at San Antonio: lead
• Janssen Scientific Affairs, LLC: collaborator

Study Sites (1)

University of Texas Health Science Center at San Antonio

San Antonio, Texas, 78229, United States

Location

Related Publications (2)

• Ali AM, Mari A, Martinez R, Al-Jobori H, Adams J, Triplitt C, DeFronzo R, Cersosimo E, Abdul-Ghani M. Improved Beta Cell Glucose Sensitivity Plays Predominant Role in the Decrease in HbA1c with Cana and Lira in T2DM. J Clin Endocrinol Metab. 2020 Oct 1;105(10):dgaa494. doi: 10.1210/clinem/dgaa494.

  PMID: 32745202 DERIVED

• Ali AM, Martinez R, Al-Jobori H, Adams J, Triplitt C, DeFronzo R, Cersosimo E, Abdul-Ghani M. Combination Therapy With Canagliflozin Plus Liraglutide Exerts Additive Effect on Weight Loss, but Not on HbA1c, in Patients With Type 2 Diabetes. Diabetes Care. 2020 Jun;43(6):1234-1241. doi: 10.2337/dc18-2460. Epub 2020 Mar 27.

  PMID: 32220916 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

Canagliflozin; Liraglutide

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Thiophenes; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Glucosides; Glycosides; Carbohydrates; Glucagon-Like Peptide 1; Glucagon-Like Peptides; Proglucagon; Gastrointestinal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Results Point of Contact

• Title: Eugenio Cersosimo, MD
• Organization: University of Texas Health San Antonio

cersosimo@uthscsa.edu

210-358-7220

Study Officials

• Eugenio Cersosimo, MD

  The University of Texas Health Science Center at San Antonio

  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: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 10, 2014
• First Posted: December 24, 2014
• Study Start: November 1, 2014
• Primary Completion: March 28, 2018
• Study Completion: March 31, 2019
• Last Updated: December 18, 2019
• Results First Posted: May 14, 2019

Record last verified: 2019-04

Locations

US (1)