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Adding SGLT2 Cotransporter Inhibitor to PPARγ Activator Does Not Provide an Additive Effect in the Management of

Aneta Cinakova1, Peter Krenek1, Jan Klimas1

  • 1Department of Pharmacology and Toxicology, Faculty of Pharmacy, Comenius University in Bratislava, Bratislava, Slovakia.

Pharmacology
|October 16, 2023
PubMed
Abstract

Insights

Pioglitazone monotherapy improved vascular function and reduced inflammation in diabetic rats, while dapagliflozin was less effective. Combination therapy showed no additive benefits for vasoreactivity or oxidative stress but did reduce IL6 levels.

Area of Science:

  • Cardiovascular Pharmacology
  • Endocrinology
  • Diabetology

Background:

  • Endothelial dysfunction (ED) is central to diabetic vascular complications.
  • Both dapagliflozin (Dapa) and pioglitazone (Pio) show therapeutic potential in monotherapy for diabetes.
  • Investigating combined SGLT2 inhibition and PPAR-γ activation for ED in type 1 diabetes (T1DM).

Purpose of the Study:

  • To evaluate the efficacy of simultaneous PPAR-γ activation and SGLT2 inhibition on endothelial dysfunction in experimental T1DM.
  • To determine if combination therapy normalizes vascular response more effectively than monotherapy.

Main Methods:

  • Experimental T1DM induced in Wistar rats using streptozotocin (STZ).
  • Administration of Dapa (10 mg/kg), Pio (12 mg/kg), or their combination orally.
  • Aorta assessment via functional studies and real-time qPCR six weeks post-STZ.

Main Results:

  • Diabetic rat aortas showed impaired relaxation, imbalanced vasoactive factors (eNos, Et1), and elevated inflammation and oxidative stress markers.
  • Pioglitazone monotherapy normalized vasoreactivity and restored Et1-eNos balance; dapagliflozin monotherapy was ineffective.
  • Both monotherapies significantly reduced inflammation and oxidative stress markers. Combination therapy showed additive IL6 reduction.

Conclusions:

  • Pioglitazone monotherapy demonstrates significant vasoprotective effects in experimental T1DM.
  • Combination therapy with dapagliflozin did not yield additive benefits in vasoreactivity or oxidative stress.
  • Combined therapy effectively influenced IL6 downregulation, suggesting a specific anti-inflammatory role.
Keywords:
DapagliflozinEndothelial dysfunctionIsolated aortaPioglitazoneRatType 1 diabetes mellitus

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