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The Pleiotropic Effects of Sodium-Glucose Cotransporter-2 Inhibitors: Beyond the Glycemic Benefit

Dhiren K Patel1, Jodi Strong2

  • 1VA Boston Healthcare System, Boston, Massachusetts, 02130, USA. dhiren.patel@va.gov.

Diabetes Therapy : Research, Treatment and Education of Diabetes and Related Disorders
|August 29, 2019
PubMed

Insights

Sodium-glucose cotransporter-2 inhibitors (SGLT-2is) offer significant cardiovascular and renal benefits beyond glucose lowering in type 2 diabetes patients. These drugs show promise for managing diabetic complications like heart failure and chronic kidney disease.

Area of Science:

  • Endocrinology
  • Cardiology
  • Nephrology

Background:

  • Type 2 diabetes (T2D) significantly elevates risks for macrovascular and microvascular complications, including cardiovascular disease (CVD), heart failure (HF), and chronic kidney disease (CKD).
  • Sodium-glucose cotransporter-2 inhibitors (SGLT-2is) uniquely address increased renal glucose reabsorption, a key factor in T2D pathophysiology.

Purpose of the Study:

  • To review the pleiotropic effects of SGLT-2 inhibitors (SGLT-2is).
  • To discuss the potential mechanisms behind these effects and their benefits beyond glycemic control in patients with T2D.
  • To highlight the potential utility of SGLT-2is in managing diabetic complications such as CVD, HF, and CKD.

Main Methods:

  • Review of cardiovascular outcomes trials (CVOTs) involving SGLT-2is (empagliflozin, canagliflozin, dapagliflozin) in patients with T2D.
  • Analysis of real-world observational studies comparing SGLT-2is with other glucose-lowering therapies.
  • Discussion of proposed mechanisms for pleiotropic effects.

Main Results:

  • CVOTs demonstrated that SGLT-2is significantly reduced composite cardiovascular and renal outcomes compared to placebo, with benefits extending beyond glucose lowering.
  • Real-world studies corroborate these findings, showing improved CV outcomes with SGLT-2is in clinical practice.
  • SGLT-2is exhibit favorable non-glycemic effects, suggesting particular benefit for patients with existing diabetic complications.

Conclusions:

  • SGLT-2is provide significant cardiovascular and renal protection in patients with T2D, independent of glycemic control.
  • The pleiotropic effects of SGLT-2is suggest a crucial role in managing complex diabetic complications.
  • Ongoing trials will further clarify the benefits and mechanisms of SGLT-2is in specific patient populations with CVD, HF, or CKD.
Keywords:
Cardiovascular diseaseChronic kidney diseasePleiotropic effectsSodium–glucose cotransporter-2 inhibitorsType 2 diabetes

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