The potential for improved outcomes in the prevention and therapy of diabetic kidney disease through 'stacking' of drugs from different classes

Diabetes Obes Metab. 2024 Jun;26(6):2046-2053. doi: 10.1111/dom.15559. Epub 2024 Mar 22.

Abstract

Aggressive therapy of diabetic kidney disease (DKD) can not only slow the progression of DKD to renal failure but, if utilized at an early enough stage of DKD, can also stabilize and/or reverse the decline in renal function. The currently recognized standard of therapy for DKD is blockade of the renin-angiotensin system with angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs). However, unless utilized at a very early stage, monotherapy with these drugs in DKD will only prevent or slow the progression of DKD and will neither stabilize nor reverse the progression of DKD to renal decompensation. Recently, the addition of a sodium-glucose cotransporter-2 inhibitor and/or a mineralocorticoid receptor blocker to ACE inhibitors or ARBs has been clearly shown to further decelerate the decline in renal function. The use of glucagon-like peptide-1 (GLP-1) agonists shown promise in decelerating the progression of DKD. Other drugs that may aid in the deceleration the progression of DKD are dipeptidyl peptidase-4 inhibitors, pentoxifylline, statins, and vasodilating beta blockers. Therefore, aggressive therapy with combinations of these drugs (stacking) should improve the preservation of renal function in DKD.

Keywords: DPP‐4 inhibitors; GLP‐1 receptor agonists; SGLT2 inhibitors; blockers on the renin‐angiotensin system (RAS blockers); carvedilol; mineralocorticoid receptor antagonists (MRAs); pentoxifylline; statins.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin Receptor Antagonists / therapeutic use
  • Angiotensin-Converting Enzyme Inhibitors* / therapeutic use
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / drug therapy
  • Diabetic Nephropathies* / drug therapy
  • Diabetic Nephropathies* / prevention & control
  • Dipeptidyl-Peptidase IV Inhibitors / therapeutic use
  • Disease Progression
  • Drug Therapy, Combination*
  • Glucagon-Like Peptide 1 / agonists
  • Glucagon-Like Peptide 1 / therapeutic use
  • Humans
  • Hypoglycemic Agents / therapeutic use
  • Mineralocorticoid Receptor Antagonists* / therapeutic use
  • Renin-Angiotensin System / drug effects
  • Sodium-Glucose Transporter 2 Inhibitors* / therapeutic use
  • Treatment Outcome

Substances

  • Angiotensin-Converting Enzyme Inhibitors
  • Sodium-Glucose Transporter 2 Inhibitors
  • Mineralocorticoid Receptor Antagonists
  • Angiotensin Receptor Antagonists
  • Glucagon-Like Peptide 1
  • Hypoglycemic Agents
  • Dipeptidyl-Peptidase IV Inhibitors