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

Type 2 Diabetes Mellitus Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02324842
• Other study ID #: 28431754DIA4009
• Secondary ID: HSC20140322H
• Status: Completed
• Phase: N/A
• Start date: November 2014
• Est. completion date: March 31, 2019

Study information

• Verified date: April 2019
• Source: The University of Texas Health Science Center at San Antonio
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

Specific Aim 1.To examine whether the combination of liraglutide plus canagliflozin can prevent the increase in HGP following institution of canagliflozin therapy and produce an additive or even synergistic effect to lower the plasma glucose concentration and A1c. We will examine this hypothesis by comparing the effect of administration of liraglutide alone, canagliflozin alone, and the combination of liraglutide plus canagliflozin on:(i) the rate of HGP; (ii) decrease in fasting plasma glucose concentration; (iii) counter-regulatory hormone response and (iv) A1c. We anticipate that the addition of liraglutide to canagliflozin will prevent the increase in plasma glucagon concentration, augment insulin secretion, and blunt/block the increase in HGP in response to canagliflozin, resulting in a greater decrease in fasting plasma glucose concentration and A1c than observed with each therapy alone.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 45
• Est. completion date: March 31, 2019
• Est. primary completion date: March 28, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 2
• Type 2 Diabetes Mellitus

Intervention

Drug:
• Canagliflozin
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)
• Liraglutide
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.

Locations

Country	Name	City	State
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas

Sponsors (2)

Lead Sponsor	Collaborator
The University of Texas Health Science Center at San Antonio	Janssen Scientific Affairs, LLC

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change in Matsuda Index of Insulin Sensitivity, Insulin Secretion, and Beta Cell Function During Oral Glucose Tolerance Test (OGTT)	Values will be presented as the mean + SD. The Matsuda Index is a novel assessment of insulin sensitivity that is simple to calculate and provides a reasonable approximation of whole-body insulin sensitivity from the OGTT. The index is calculated from plasma glucose (mg/dl) and insulin (mIU/l) concentrations in both fasting state and post-OGTT. The index value obtained is compared to normal physiologic values to assess insulin sensitivity or resistance. The higher the number, the more insulin sensitive and the lower the number the more insulin resistant the subjects are. Insulin secretion will be measured from plasma C-peptide concentration during the OGTT and the Mari Model will be used to measure beta cell glucose sensitivity	Change from Baseline to Approximately 4 months
Other	Change in Free Plasma Insulin at the End of the Study From Baseline Value	Values will be presented as the mean + 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.	At Approximately 4 months
Other	Change in Plasma Glucagon Concentration at the End of the Study Compared to Baseline	Values will be presented as the mean + 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.	Approximately 4 months
Other	Change in Total Body Weight at Study End Compared to Baseline	Values will be presented as the mean + 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. The difference between baseline and study end will represent the change in body weight due to change in hepatic, visceral and abdominal subcutaneous fat.	Approximately 4 months
Other	Change in 24-hour Blood Pressure at Study End Compared to Baseline.	Values will be presented as the mean + 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.	Approximately 4 months
Primary	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
Primary	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	Body Mass Index (BMI) at 4 Months	A measure of BMI at 4 months to examine effects of combination therapy with liraglutide plus canagliflozin.	Approximately 4 months