Effect of Combined Incretin-Based Therapy Plus Canagliflozin on Glycemic Control and the Compensatory Rise in Hepatic Glucose Production in Type 2 Diabetic Patients
Condition: Type 2 Diabetes Mellitus
MeSH terms: Diabetes Mellitus, Type 2
Study type: Interventional

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.
    

Detailed 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.
    

Intervention name(s): Canagliflozin; Liraglutide
Intervention type(s): Drug; Drug
Intervention description(s): 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 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.
Other intervention name(s): Invokana; Victoza
Intervention MeSH terms: Liraglutide; Canagliflozin
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment