Use of Anti-Diabetic Agents in Non-Diabetic Kidney Disease: From Bench to Bedside
New drugs were recently developed to treat hyperglycemia in patients with type 2 diabetes mellitus (T2D). However, metformin remains the first-line anti-diabetic agent because of its cost-effectiveness. It has pleiotropic action that produces cardiovascular benefits, and it can be useful in diabetic...
| Main Authors: | , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-04-01
|
| Series: | Life |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2075-1729/11/5/389 |
| _version_ | 1797536339993821184 |
|---|---|
| author | Sungjin Chung Gheun-Ho Kim |
| author_facet | Sungjin Chung Gheun-Ho Kim |
| author_sort | Sungjin Chung |
| collection | DOAJ |
| description | New drugs were recently developed to treat hyperglycemia in patients with type 2 diabetes mellitus (T2D). However, metformin remains the first-line anti-diabetic agent because of its cost-effectiveness. It has pleiotropic action that produces cardiovascular benefits, and it can be useful in diabetic nephropathy, although metformin-associated lactic acidosis is a hindrance to its use in patients with kidney failure. New anti-diabetic agents, including glucagon-like peptide-1 receptor (GLP-1R) agonists, dipeptidyl peptidase-4 (DPP-4) inhibitors, and sodium-glucose transporter-2 (SGLT-2) inhibitors, also produce cardiovascular or renal benefits in T2D patients. Their glucose-independent beneficial actions can lead to cardiorenal protection via hemodynamic stabilization and inflammatory modulation. Systemic hypertension is relieved by natriuresis and improved vascular dysfunction. Enhanced tubuloglomerular feedback can be restored by SGLT-2 inhibition, reducing glomerular hypertension. Patients with non-diabetic kidney disease might also benefit from those drugs because hypertension, proteinuria, oxidative stress, and inflammation are common factors in the progression of kidney disease, irrespective of the presence of diabetes. In various animal models of non-diabetic kidney disease, metformin, GLP-1R agonists, DPP-4 inhibitors, and SGLT-2 inhibitors were favorable to kidney morphology and function. They strikingly attenuated biomarkers of oxidative stress and inflammatory responses in diseased kidneys. However, whether those animal results translate to patients with non-diabetic kidney disease has yet to be evaluated. Considering the paucity of new agents to treat kidney disease and the minimal adverse effects of metformin, GLP-1R agonists, DPP-4 inhibitors, and SGLT-2 inhibitors, these anti-diabetic agents could be used in patients with non-diabetic kidney disease. This paper provides a rationale for clinical trials that apply metformin, GLP-1R agonists, DPP-4 inhibitors, and SGLT-2 inhibitors to non-diabetic kidney disease. |
| first_indexed | 2024-03-10T11:58:18Z |
| format | Article |
| id | doaj.art-c5f7918752c94066a8113fc7ceddf073 |
| institution | Directory Open Access Journal |
| issn | 2075-1729 |
| language | English |
| last_indexed | 2024-03-10T11:58:18Z |
| publishDate | 2021-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Life |
| spelling | doaj.art-c5f7918752c94066a8113fc7ceddf0732023-11-21T17:07:58ZengMDPI AGLife2075-17292021-04-0111538910.3390/life11050389Use of Anti-Diabetic Agents in Non-Diabetic Kidney Disease: From Bench to BedsideSungjin Chung0Gheun-Ho Kim1Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul 06591, KoreaDepartment of Internal Medicine, Hanyang University College of Medicine, Seoul 04763, KoreaNew drugs were recently developed to treat hyperglycemia in patients with type 2 diabetes mellitus (T2D). However, metformin remains the first-line anti-diabetic agent because of its cost-effectiveness. It has pleiotropic action that produces cardiovascular benefits, and it can be useful in diabetic nephropathy, although metformin-associated lactic acidosis is a hindrance to its use in patients with kidney failure. New anti-diabetic agents, including glucagon-like peptide-1 receptor (GLP-1R) agonists, dipeptidyl peptidase-4 (DPP-4) inhibitors, and sodium-glucose transporter-2 (SGLT-2) inhibitors, also produce cardiovascular or renal benefits in T2D patients. Their glucose-independent beneficial actions can lead to cardiorenal protection via hemodynamic stabilization and inflammatory modulation. Systemic hypertension is relieved by natriuresis and improved vascular dysfunction. Enhanced tubuloglomerular feedback can be restored by SGLT-2 inhibition, reducing glomerular hypertension. Patients with non-diabetic kidney disease might also benefit from those drugs because hypertension, proteinuria, oxidative stress, and inflammation are common factors in the progression of kidney disease, irrespective of the presence of diabetes. In various animal models of non-diabetic kidney disease, metformin, GLP-1R agonists, DPP-4 inhibitors, and SGLT-2 inhibitors were favorable to kidney morphology and function. They strikingly attenuated biomarkers of oxidative stress and inflammatory responses in diseased kidneys. However, whether those animal results translate to patients with non-diabetic kidney disease has yet to be evaluated. Considering the paucity of new agents to treat kidney disease and the minimal adverse effects of metformin, GLP-1R agonists, DPP-4 inhibitors, and SGLT-2 inhibitors, these anti-diabetic agents could be used in patients with non-diabetic kidney disease. This paper provides a rationale for clinical trials that apply metformin, GLP-1R agonists, DPP-4 inhibitors, and SGLT-2 inhibitors to non-diabetic kidney disease.https://www.mdpi.com/2075-1729/11/5/389dipeptidyl peptidase-4 inhibitorglucagon-like peptide-1 receptor agonistinflammationmetforminoxidative stresssodium-glucose transporter-2 inhibitor |
| spellingShingle | Sungjin Chung Gheun-Ho Kim Use of Anti-Diabetic Agents in Non-Diabetic Kidney Disease: From Bench to Bedside Life dipeptidyl peptidase-4 inhibitor glucagon-like peptide-1 receptor agonist inflammation metformin oxidative stress sodium-glucose transporter-2 inhibitor |
| title | Use of Anti-Diabetic Agents in Non-Diabetic Kidney Disease: From Bench to Bedside |
| title_full | Use of Anti-Diabetic Agents in Non-Diabetic Kidney Disease: From Bench to Bedside |
| title_fullStr | Use of Anti-Diabetic Agents in Non-Diabetic Kidney Disease: From Bench to Bedside |
| title_full_unstemmed | Use of Anti-Diabetic Agents in Non-Diabetic Kidney Disease: From Bench to Bedside |
| title_short | Use of Anti-Diabetic Agents in Non-Diabetic Kidney Disease: From Bench to Bedside |
| title_sort | use of anti diabetic agents in non diabetic kidney disease from bench to bedside |
| topic | dipeptidyl peptidase-4 inhibitor glucagon-like peptide-1 receptor agonist inflammation metformin oxidative stress sodium-glucose transporter-2 inhibitor |
| url | https://www.mdpi.com/2075-1729/11/5/389 |
| work_keys_str_mv | AT sungjinchung useofantidiabeticagentsinnondiabetickidneydiseasefrombenchtobedside AT gheunhokim useofantidiabeticagentsinnondiabetickidneydiseasefrombenchtobedside |