Table 1.

Review of the main clinical trials that analyzed the impact of GLP-IRA on renal outcomes (adapted from Granata et al. [11])

	Drug	Renal endpoint	Results
LEADER	Liraglutide versus placebo	- Macroalbuminuria - Doubling of sCreat - eGFR <45 mL/min/1.73 m2 - Need for dialysis - Death for renal causes	A lower incidence of nephropathy was found in the group treated with liraglutide, due to a favourable impact on macroalbuminuria. The eGFR decline over time was slower in patients with moderate/severe CKD.
SCALE	Liraglutide versus placebo	- Changes in UACR	A significant weight loss also but a decreased urinary albumin/creatinine ratio (UACR) was observed in both liraglutide arms compared with placebo (18.36, 10.79 and 2.34%, respectively).
LIRA-RENAL	Liraglutide versus placebo	- Changes in eGFR - Changes in UACR	There was no difference between liraglutide and placebo in terms of eGFR and UACR. This result could be partly due to the small size of the sample and the short observation period.
SUSTAIN–6	Semaglutide versus placebo	- Macroalbuminuria - Doubling of sCreat - eGFR <45 mL/min/1.73 m2 - Need for dialysis	Semaglutide reduces the incidence of de novo macroalbuminuria. Nevertheless, no difference was found regarding the incidence of ESRD and death for renal causes.
ELIXA	Lixisenatide versus placebo	- Changes in UACR	Lixisenatide slows the worsening of UACR over time regardless of basal albuminuria. No difference was found regarding eGFR decline rate.
EXSCEL	Exenatide LAR versus placebo	- 40% eGFR decline - Need for dialysis - Death for renal causes - Macroalbuminuria de novo	Exenatide LAR performs better than placebo regarding the composite renal outcome, with greater efficacy on the incidence of macroalbuminuria.
AWARD-7	Dulaglutide versus glargine	- Changes in eGFR and UACR from baseline	Dulaglutide was more effective than insulin glargine in attenuating the decline in renal function, while there were no statistically significant differences on the reduction of UACR. The authors did not observe any significant correlation between the variation of creatinine, cystatin C and body weight.
REWIND	Dulaglutide versus Placebo	- Macroalbuminuria de novo - ≥30% eGFR decline from baseline - Need for dialysis	Although the incidence of macroalbuminuria was lower in the dulaglutide group, the percentages of eGFR decline ≥30% and the need for dialysis showed an almost comparable trend in the two groups. Sensitivity analysis revealed that dulaglutide significantly reduces the worsening eGFR when it is defined as a reduction of ≥40% or ≥50%, rather than ≥30%.

Abbreviations: CKD, chronic kidney disease; eGFR, estimated glomerular filtration rate; ESRD, end-stage renal disease; sCreat, serum creatinine; UACR, urine albumin/creatinine ratio.