DPP4 Inhibitors in Chronic Kidney Disease and Their Potential to Protect Against Diabetic Nephropathy
Preclinical and clinical observations suggest that dipeptidyl peptidase 4 (DPP4) inhibitors might offer additional benefits to patients apart from effective and safe glycemic control.
The Threat of Diabetic Nephropathy
Type 2 diabetes mellitus is associated with a high risk of kidney disease. Up to 40% of type 2 diabetics suffer from chronic kidney disease (CKD), with 20% having CKD stage 3 or higher. Despite exhaustive searches for nephroprotective agents to prevent or treat diabetic nephropathy, renin-angiotensin-aldosterone system inhibitors remain the sole pillar of this treatment. However, some oral antidiabetics, including DPP4 inhibitors, show promising results.
Effect and Use in CKD
By inhibiting the enzyme responsible for the degradation of incretins, DPP4 inhibitors achieve good control of both fasting and postprandial glycemia with minimal risk of hypoglycemia. These substances are an effective and well-tolerated treatment option for type 2 diabetics with either healthy kidneys or any degree of CKD. When administered to CKD patients, dose reductions corresponding to the degree of kidney impairment are recommended for all molecules except linagliptin, which is minimally excreted by the kidneys. For diabetics with severe kidney damage, DPP4 inhibitors remain the only option to manage diabetes, aside from insulin. Linagliptin is the only oral antidiabetic that can even be used in dialysis patients.
Their potential additional benefit in preventing and/or treating diabetic nephropathy has been suggested by several preliminary observations. Large prospective studies are currently underway. Consistent observation during DPP4 inhibitor treatment shows stagnation or improvement in albuminuria values, indicating their protective effect on the kidneys. This trait appears to be independent of the degree of glycemic reduction. Available data predominantly speak about linagliptin and saxagliptin, but the comprehensiveness of the data suggests a possible class effect for the entire group of DPP4 inhibitors.
Promising Trends Awaiting Verification
In addition to effective glycemic control, DPP4 inhibitors may provide patients with a "bonus" in the form of direct protection against diabetic nephropathy. They could become an adjunct to current therapeutic strategies aimed at preserving renal function in type 2 diabetes. These are very promising conclusions, but they should be approached with caution and await confirmation from larger, ongoing studies.
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Sources:
1. Penno G., Garofolo M., Del Prato S. Dipeptidyl peptidase-4 inhibition in chronic kidney disease and potential for protection against diabetes-related renal injury. Nutr Metab Cardiovasc Dis 2016 May; 26 (5): 361–373, doi: 10.1016/j.numecd.2016.01.001.
2. Szabó M. Dipeptidyl peptidase 4 inhibitors. Internal Medicine 2013; 15 (2): 49–50.
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