Supplemental Fig. S2
Funnel plots for changes in urine albumin-to-creatinine ratio and estimated glomerular filtration rates in dipeptidyl peptidase-4 inhibitors versus placebo or other antidiabetic agents. (A) Changes in urine albumin-to-creatinine ratio, ●, non-sodium-glucose cotransporter 2 inhibitors; ▲, sodium-glucose cotransporter 2 inhibitors. (B) Changes in estimated glomerular filtration rate, ●, controls; CI, confidence interval.
enm-34-80-s004.pdf
Supplemental Fig. S3
Sensitivity analyses excluding individual studies for the development of microalbuminuria, macroalbuminuria, regression of albuminuria, and end-stage renal disease. (A) Microalbuminuria, (B) macroalbuminuria, and (C) regression of albuminuria. CI, confidence interval.
enm-34-80-s005.pdf
Fig. 1Flow diagram of study screening and selection process.
Fig. 2Standardized mean differences in changes in urine albumin-to-creatinine ratio (UACR) from baseline (mg/g) for dipeptidyl peptidase-4 (DPP-4) inhibitors versus placebo or other antidiabetic agents, according to non-sodium-glucose cotransporter 2 inhibitors and sodium-glucose cotransporter 2 inhibitors in the control group. Trt, treatment group; Con, control group; SD, standard deviation; ES, effect size; CI, confidence interval; SGLT2, sodium-glucose cotransporter 2; OHA, oral hypoglycemic agent; NR, not reported.
Fig. 3Weighted mean differences in changes in estimated glomerular filtration rate from baseline (mL/min/1.73 m2) for dipeptidyl peptidase-4 (DPP-4) inhibitors versus placebo or other antidiabetic agents. Trt, treatment group; Con, control group; SD, standard deviation; ES, effect size; CI, confidence interval; NR, not reported.
Fig. 4Relative risks of incident albuminuria, regression of albuminuria, and end-stage renal disease for dipeptidyl peptidase-4 (DPP-4) inhibitors versus placebo or other antidiabetic agents. (A) Microalbuminuria, (B) macroalbuminuria, (C) regression of albuminuria, and (D) end-stage renal disease. Trt, treatment group; Con, control group; RR, relative risk; CI, confidence interval.
Table 1Characteristics of Included Studies in the Systematic Review and Meta-Analysis
Study |
Intervention |
Control |
Background antidiabetic agents |
Length of follow-up, wk |
Number |
Mean age, yr |
Baseline eGFR, mL/min/1.73 m2
|
Cornel et al. (2016) [12]a
|
Sitagliptin |
Placebo |
OADs (except rosiglitazone)±insulin |
4 yr |
14,671 |
65.5 |
≥30 |
Green et al. (2015) [14]b
|
Sitagliptin |
Placebo |
OADs (except rosiglitazone)±insulin |
4 yr |
14,671 |
65.5 |
≥30 |
Groop et al. (2013) [23] |
Linagliptin |
Placebo |
None OR Metformin OR Metformin+SU |
24 |
217 |
60.4 |
≥30 |
Groop et al. (2017) [15] |
Linagliptin |
Placebo |
None OR OADs±insulin |
24 |
360 |
60.6 |
≥30 |
Mosenzon et al. (2017) [11] |
Saxagliptin |
Placebo |
OADs±insulin |
2.1 yr (median) |
16,492 |
- |
SCr <530 µmol/L |
White et al. (2013) [39] |
Alogliptin |
Placebo |
OADs±insulin |
160 |
5,380 |
61.0 (median) |
No limit |
Yoon et al. (2017) [40] |
Gemigliptin |
Placebo |
None OR Insulin±SU |
12 |
132 |
62.0 |
≥15, <30 |
DeFronzo et al. (2015) [30] |
Linagliptin |
Empagliflozin |
Metformin |
52 |
413 |
56.0 |
≥60 |
Lavalle-Gonzalez et al. (2013) [31] |
Sitagliptin |
Canagliflozin OR Placebo |
Metformin |
52 |
1,101 |
55.5 |
≥55 |
Lewin et al. (2015) [32] |
Linagliptin |
Empagliflozin |
None |
52 |
398 |
54.4 |
≥60 |
Nakamura et al. (2014) [38] |
Sitagliptin |
Voglibose |
Metformin±SU±TZD |
12 |
66 |
67.5 |
SCr <133 µmol/L |
Mori et al. (2014) [28] |
Sitagliptin |
Metformin OR Glinides OR Alpha-glucosidase inhibitor |
TZD±SU |
24 |
85 |
64.2 |
SCr <133 µmol/L (men), <124 µmol/L (women) |
Nomoto et al. (2016) [36] |
Sitagliptin |
Glimepiride |
None OR Metformin |
26 |
103 |
59.9 |
NR |
Nomoto et al. (2017) [29] |
DPP-4 inhibitors |
Dapagliflozin |
Insulin±OADs |
12 |
36 |
61.5 |
≥45 |
Roden et al. (2013) [41] |
Sitagliptin |
(a) Empagliflozin OR (b) Placebo |
None |
24 |
899 |
55.0 |
≥50 |
Schernthaner et al. (2013) [33] |
Sitagliptin |
Canagliflozin |
Metformin+SU |
52 |
756 |
56.7 |
≥55 |
Takihata et al. (2013) [35] |
Sitagliptin |
Pioglitazone |
Metformin±SU |
24 |
130 |
60.5 |
≥30 |
Tonneijck et al. (2016) [34] |
Sitagliptin |
Liraglutide OR Placebo |
Metformin±SU |
12 |
56 |
62.4 |
≥60 |
Zografou et al. (2015) [37] |
Vildagliptin+Metformin |
Metformin |
None |
24 |
64 |
54.0 |
NR |