Table 1.
Summary of renal effects of hypoglycemic drugs on nephroprotection: experimental and clinical studies.
| Drug | Direct Renal Nephroprotective Mechanisms | Indirect Nephroprotective Mechanisms (Apart from Glycaemic Control) | Nephroprotective Effect in Clinical Studies | Clinical Trials |
|---|---|---|---|---|
| Insulin | ↓insulin sensitivity is associated with ↑risk of albuminuria [15] | Indirect data from UKPDS study | Not done | |
| Metformin | Reducing vascular dysfunction and oxidative stress in rats [19,20,21] | Cardiovascular benefit | Not done | Not done |
| Sulphonylureas | ↓proteinuria IN animal models: Improvement in histological glomerular lesions, promotion of tubular reabsorption of some biomarkers by↓expression of PKC-β, PKA, megalin and cubilin [23] | No effect on albuminuria [24] | ||
| α-Glucosidase inhibitors | Up-regulates GLP-1 production and IGF-1 in experimental models [26] | Not done | Not done | |
| Metiglinides (repaglinide) | No differences in albuminuria compared with metformin or insulin [26] | Not done | ||
| Thiazolidinediones | Improving insulin sensitivity. Inhibition of TNF-α [34] Improving histological lesions, decrease proteinuria and and restore podocyte in animal models [29,30,31] |
Improvement of metabolic síndrome and cardiovascular risk factors [29,30] | Heterogeneus response in albuminuria Benefit decreasing albuminuria in meta-analysis Conflicting results Small number of patients [33,34,35,36,37] |
Not done |
| DPP-4 inhibitors | Ameliorating histological lesions in rats [55] ↓IL-1β, ↓TNF-α, ↓Bid protein levels in experimental studies [60] |
Sitagliptin decreases albuminuria after 6 moths of treatment [65,66,67] | MARLINA trial (on going) | |
| GLP-1R analogs | Ameliorated renal histological lesions in animal models [74] Promoting natriuresis acting in proximal tubule in humans [77] restoring tubulo-glomerular feedback [81] |
Reducing blood pressure and increasing natriuresis [78] | Exenatide reduces albuminuria and TFG-β1 and type IV collagen excretion and microalbuminuria compared to glimepiride in patients with type 2 diabetes mellitus [68] | Not done |
| SGLT2 inhibitors | -Attenuating diabetes-associated hyperfiltration and tubular hypertrophy (Thomas) -Reducing the tubular toxicity of glucose - Reducing single-nephron glomerular filtration rate - In experimental diabetes reduce albuminuria and markers of renal inflammation - In animal models SGLT2 inhibits inflammatory response in kidney (TGF-β, MCP-1), and ↓apoptosis rates - Restoring tubuloglomerular feedback [92,93,98] |
Decreasing weight and blood pressure, improving glycaemic control and increase in sodium excretion | Not done | CREDENCE trial (On going). Indirect data from previous clinical trials |
DPP-4: dipeptidyl peptidase-4; GLP-1R: glucagon-like peptide-1 receptor; SGLT2: Sodium-glucose cotransporter-2; References are in brackets.