. 2019 Dec 20;11(2):369–386. doi: 10.1007/s13300-019-00747-3

Table 3.

Renal outcomes in incretin-based therapy cardiovascular outcome trials

Trial	Composite renal outcome measure	Progression of albuminuria	eGFR/creatinine	Incidence of ESRD	Death from a renal cause
EXAMINE trial (alogliptin) n = 5380	Not reported	Not reported	Alogliptin vs placebo^a: eGFR < 30: + 0.2 vs + 1.6 eGFR 30−59: + 1.1 vs + 2.1 eGFR 60–89: + 0.6 vs + 1.0 eGFR ≥ 90: − 6.7 vs. − 4.5	Alogliptin: 0.9% Placebo: 0.8%	Not reported
SAVOR-TIMI 53 (saxagliptin) n = 16,492	Saxagliptin: 2.2% Placebo: 2.0: (HR 1.08)	Worsened UACR: Saxagliptin: 13.3% Placebo: 15.9%	Saxagliptin: 2.02% Placebo: 1.82% (HR 1.1)	Saxagliptin: 0.61% Placebo: 0.67% (HR 0.90)	Saxagliptin: 0.1% Placebo: 0.1%
TECOS trial (sitagliptin) n = 14,671	Not reported	Sitagliptin: − 0.18 mg/g vs placebo	Sitagliptin: − 4.0^a Placebo: − 2.8^a	Not reported	Not reported
CARMELINA trial (linagliptin) n = 6979	Linagliptin: 9.4% Placebo: 8.8% (HR 1.04)	Linaglipitin: 35.3% Placebo: 38.5% (HR 0.86)	Linaglipitin: 7.5% Placebo: 6.9%	Linaglipitin: 1.8% Placebo: 1.8%	Linaglipitin: 0.03% Placebo: 0.03%
ELIXA trial (lixisenatide) n = 6068	Not reported	Mean change in urinary ACR (lixisenatide vs placebo): normoalbuminuria (− 1.69 vs − 11.69%), microalbuminuria (− 21.10 vs − 42.45%), or macroalbuminuria (− 39.18 vs − 68.53%)	Lixisenatide: 1.35% Placebo: 1.15% (HR 1.16)	Not reported	Not reported
LEADER trial (liraglutide) n = 9340	Liraglutide: 5.7% Placebo: 7.2% (HR 0.78)	Liraglutide: 3.4% Placebo: 4.6% (HR 0.74)	Liraglutide: 1.9% Placebo: 2.1% (HR 0.89)	Liraglutide: 1.2% Placebo: 1.4% (HR 0.87)	Liraglutide: 0.17% Placebo: 0.11% (HR 1.59)
SUSTAIN-6 trial (semaglutide) n = 3297	Semaglutide: 3.8% Placebo: 6.1% (HR 0.64)	Semaglutide: 2.7% Placebo: 4.9% (HR 0.54)	Semaglutide: 1.1% Placebo: 0.8% (HR 1.28)	Semaglutide: 0.7% Placebo: 0.7% (HR 0.91)	Not reported
PIONEER-6 (semaglutide) n = 3183	Not reported	Not reported	eGFR ratio (baseline:end of study) Exenatide: 0.98 Placebo: 0.98	Not reported	Semaglutide: 0% Placebo: 0.1%
EXSCEL trial (exenatide) n = 14,752	Exenatide: 5.8% Placebo: 6.5% (HR 0.85)	Exenatide: 2.2% Placebo: 2.8%	Exenatide: 3.5% Placebo: 4.6%	Exenatide: 0.7% Placebo: 0.9%	Exenatide: 1.0% Placebo: 0.9%
HARMONY Outcomes (albiglutide) n = 9463	Not reported	Not reported	Change in GFR (albiglutide vs placebo): 8 months: − 1.11^a 16 months: − 0.43^a	Not reported	Not reported
REWIND study (dulaglutide) n = 9901	Dulaglutide: 17.1% Placebo: 19.6% (HR 0.85)	Dulaglutide: 8.9% Placebo: 11.3% (HR 0.77)	Dulaglutide: 9.2% Placebo: 10.1% (HR 0.89)	Dulaglutide: 0.3% Placebo: 0.4% (HR 0.75)	Not reported

Trial

Composite renal outcome measure

Progression of albuminuria

eGFR/creatinine

Incidence of ESRD

Death from a renal cause

EXAMINE trial (alogliptin)

n = 5380

Not reported

Alogliptin vs placebo^a: eGFR < 30: + 0.2 vs + 1.6

eGFR 30−59: + 1.1 vs + 2.1

eGFR 60–89: + 0.6 vs + 1.0

eGFR ≥ 90: − 6.7 vs. − 4.5

Alogliptin: 0.9%

Placebo: 0.8%

Not reported

SAVOR-TIMI 53 (saxagliptin)

n = 16,492

Saxagliptin: 2.2%

Placebo: 2.0:

(HR 1.08)

Worsened UACR:

Saxagliptin: 13.3%

Placebo: 15.9%

Saxagliptin: 2.02%

Placebo: 1.82%

(HR 1.1)

Saxagliptin: 0.61%

Placebo: 0.67%

(HR 0.90)

Saxagliptin: 0.1%

Placebo: 0.1%

TECOS trial (sitagliptin)

n = 14,671

Not reported

Sitagliptin: − 0.18 mg/g vs placebo

Sitagliptin: − 4.0^a

Placebo: − 2.8^a

Not reported

CARMELINA trial (linagliptin)

n = 6979

Linagliptin: 9.4%

Placebo: 8.8%

(HR 1.04)

Linaglipitin: 35.3%

Placebo: 38.5%

(HR 0.86)

Linaglipitin: 7.5%

Placebo: 6.9%

Linaglipitin: 1.8%

Placebo: 1.8%

Linaglipitin: 0.03%

Placebo: 0.03%

ELIXA trial (lixisenatide)

n = 6068

Not reported

Mean change in urinary ACR (lixisenatide vs placebo): normoalbuminuria (− 1.69 vs − 11.69%),

microalbuminuria (− 21.10 vs − 42.45%), or macroalbuminuria (− 39.18 vs − 68.53%)

Lixisenatide: 1.35%

Placebo: 1.15% (HR 1.16)

Not reported

LEADER trial (liraglutide)

n = 9340

Liraglutide: 5.7%

Placebo: 7.2% (HR 0.78)

Liraglutide: 3.4%

Placebo: 4.6% (HR 0.74)

Liraglutide: 1.9%

Placebo: 2.1% (HR 0.89)

Liraglutide: 1.2%

Placebo: 1.4% (HR 0.87)

Liraglutide: 0.17%

Placebo: 0.11% (HR 1.59)

SUSTAIN-6 trial (semaglutide)

n = 3297

Semaglutide: 3.8%

Placebo: 6.1% (HR 0.64)

Semaglutide: 2.7%

Placebo: 4.9% (HR 0.54)

Semaglutide: 1.1%

Placebo: 0.8% (HR 1.28)

Semaglutide: 0.7%

Placebo: 0.7% (HR 0.91)

Not reported

PIONEER-6 (semaglutide)

n = 3183

Not reported

eGFR ratio (baseline:end of study)

Exenatide: 0.98

Placebo: 0.98

Not reported

Semaglutide: 0%

Placebo: 0.1%

EXSCEL trial (exenatide)

n = 14,752

Exenatide: 5.8%

Placebo: 6.5% (HR 0.85)

Exenatide: 2.2%

Placebo: 2.8%

Exenatide: 3.5%

Placebo: 4.6%

Exenatide: 0.7%

Placebo: 0.9%

Exenatide: 1.0%

Placebo: 0.9%

HARMONY Outcomes (albiglutide)

n = 9463

Not reported

Change in GFR (albiglutide vs placebo): 8 months: − 1.11^a

16 months: − 0.43^a

Not reported

REWIND study (dulaglutide)

n = 9901

Dulaglutide: 17.1%

Placebo: 19.6% (HR 0.85)

Dulaglutide: 8.9%

Placebo: 11.3% (HR 0.77)

Dulaglutide: 9.2%

Placebo: 10.1% (HR 0.89)

Dulaglutide: 0.3%

Placebo: 0.4% (HR 0.75)

Not reported

The number of participants in each trial is denoted by n

eGFR estimated glomerular filtration rate, ESRD end-stage renal disease, HR hazard ratio, ACR albumin-to-creatinine ratio

^aUnits ml/min/1.73 m²