Effect of Farxiga on Renal Function and Size in Type 2 Diabetic Patients With Hyperfiltration
Condition: Diabetes Mellitus, Type 2
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Study type: Interventional
Phase: Phase 4

Summary: 
      The investigators propose to treat newly diagnosed, hyperfiltering T2DM patients with or
      without microalbuminuria with dapagliflozin or metformin for 4 months. The metformin-treated
      group will serve as controls for improved glycemic control, since the investigators have
      shown that insulin therapy to normalize A1c reduces hyperfiltration and kidney size in T1DM
      patients.
    

Detailed description: 
      Hyperfiltration is a characteristic feature in experimental models of diabetes and is
      causally related to an increase in intraglomerular pressure. In newly diagnosed diabetic
      patients, both type 1 and type 2, hyperfiltration and enlarged kidney size commonly are
      observed, and these hemodynamic/anatomic abnormalities are associated with an increased risk
      for the development of diabetic nephropathy.

      In poorly controlled diabetic individuals, the filtered load of glucose is markedly increased
      and glucose - with sodium - reabsorption by the SGLT2 transporter in the proximal tubule is
      augmented. As a consequence sodium delivery to the macula densa is reduced, making the kidney
      think that it is under perfused and this results in afferent renal arteriolar vasodilation.
      The efferent arteriole of the hyperfiltrating diabetic kidney also is hypersensitive to
      angiotensin II despite the absence of systemic RAS activation. The net result of these
      hemodynamic changes is an increase in intraglomerular pressure and hyperfiltration. Further,
      angiotensin is a potent growth factor and contributes to the increase in size of individual
      glomeruli and total kidney size. Since the intraglomerular pressure is related to the radius
      (r3) by the Law of LaPlace, the increase in glomerular size also contributes to
      hyperfiltration.

      Based upon the preceding sequence, it follows that a drug that blocks glucose, along with
      sodium, reabsorption in the proximal tubule would enhance sodium delivery to the macula
      densa, cause afferent renal arteriolar constriction, reduce intraglomerular
      pressure/hyperfiltration, and decrease kidney size. In hyperfiltering diabetic patients with
      microalbuminuria, the investigators also would expect the microalbuminuria to decrease.
      Consistent with this scenario, animal studies have documented that both acute and chronic
      inhibition of SGLT2 decreases hyperfiltration and prevents diabetic nephropathy. A recent
      study in hyperfiltering type 1 diabetic patients treated with empagliflozin has provided
      additional support for the tubular glomerular feedback hypothesis.

      The investigators propose to treat newly diagnosed, hyperfiltering T2DM patients with or
      without microalbuminuria with dapagliflozin or metformin for 4 months. The metformin-treated
      group will serve as controls for improved glycemic control, since the investigators have
      shown that insulin therapy to normalize A1c reduces hyperfiltration and kidney size in T1DM
      patients
    

Intervention name(s): Dapagliflozin; Metformin; Glipizide 5 MG
Intervention type(s): Drug; Drug; Drug
Intervention description(s): SGLT2 inhibitor; Oral diabetes medicine that helps control blood sugar levels.; Oral diabetes medicine that helps control blood sugar levels.
Other intervention name(s): Farxiga; Metformin-XR
Intervention MeSH terms: Metformin; Dapagliflozin; Glipizide
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: hyperfiltering; Type 2 Diabetes Mellitus