• Diabetic kidney disease has a relentless progression. Despite use of ACEI/ARB, many patients continue to have persistent proteinuria (albuminuria) and progress to ESRD.
• Some antidiabetic drugs can retard progression of renal disease independent of glycemic control.
• SGLT2i reduce glomerular hyperfiltration by tubuloglomerular feedback.

1. EMPAREG renal outcomes trial with empagliflozin and CANVAS-R with canagliflozin, highlighted the renal benefits where renal outcomes were secondary end points.
2. CREDENCE trial was targeted at renal outcomes primarily while CV outcomes were secondary. CREDENCE trial showed significant renal benefits and hence had to be stopped prematurely.
3. DECLARE trial with dapagliflozin also highlighted the improved renal outcomes. DAPA-CKD is evaluating the renal outcomes in nondiabetic patients.

• GLP-1 analogs (incretin analogs) were also found to have renal effects. GLP-1 is a gut hormone which acts on the pancreas and releases insulin. It also participates in gut-renal axis and promotes natriuresis and diuresis.

1. GLP-1a may cause renoprotection, as was seen in LIRA-RENAL trial with liraglutide and AWARD trial with dulaglutide.

• DPP-4 inhibitors, popularly known as gliptins, increase GLPi and have also shown some reduction in albuminuria as shown in post-hoc analysis of some trials (SAVOR-TIMI with saxagliptin, EXAMINE with alogliptin and TECOS with sitagliptin).

1. Results of CARMELINA trial with linagliptin with predefined secondary renal outcomes have shown renal safety and also proteinuria reduction in diabetics with significant renal disease.

The renoprotective and cardioprotective benefits of SGLT2i and GLP-1a have led to change in ADA guidelines (2018), which define the choice of antidiabetic drugs. In patients with cardiac risk factors or renal risk, SGLT2i or GLP-1a may be added as second-line to metformin above other antidiabetics for CV and renal benefits. Judicious use of these drugs may help counter the menace of diabetic kidney disease.