Table 2. Summary of study characteristics: Observational Studies.
| Author
(Year) |
Number | Data source
(Country) |
Yrs of
study |
Drug
comparison |
Age (yrs) | Kidney
related exclusions |
Measures at baseline | Primary
outcomes of study |
Follow-up
(yrs) |
Kidney
outcomes recorded HR (95% CI) c |
||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Kidney | Years with
T2DM |
HbA1c % | ||||||||||
| Hung
et al.
(2012) 19 |
93577 | Veterans
Administration (US) |
2001–
2008 |
Incident MTF,
SU or RSG, excluding combination users |
Median (IQR)
MTF: 60 (55, 69) SU: 62 (56, 72) RSG: 64 (57, 72) |
eGFR <60 | Microalbuminuria
b %:
MTF: 3, SU: 3, RSG: 4 [only available for 15,065 people] Median eGFR (IQR) MTF: 81 (72, 93), SU: 80 (70, 93), RSG: 79 (69, 91) |
NR | Median (IQR):
MTF: 7.1 (6.5, 7.9) SU: 7.3 (6.6, 8.4) RSG: 6.8 (6.2, 7.6) |
1 eGFR (≥25%
decline) 2 ESRD (eGFR<15, ICD-9 codes for dialysis or renal transplant) 3 Mortality |
Median
(IQR): MTF: 0.9 (0.5, 1.8) SU: 0.8 (0.4, 1.7) RSG: 0.7 (0.3, 1.5) |
eGFR event
or ESRD Referent MTF SU: 1.20, (1.13, 1.28), RSG: 0.92, (0.71, 1.18) eGFR event, ESRD or mortality Referent MTF: SU 1.20, (1.13, 1.28), RSG: 0.89, (0.69, 1.12) |
| Currie
et al.
(2013) 21 |
84,622 | CPRD GOLD
datalink (UK) |
2000–
2010 |
MTF, SU,
MTF+SU |
Mean
(median) 61.9 (12.8) |
None stated | Creatinine
>130 µmol/L: 4.5% |
Mean:
2.3 (SD 3.0) |
Mean (SD):
8.7 (1.9) |
Renal failure
(Read codes) |
Mean: 2.8 |
Renal failure
Referent: MTF SU: 2.63 (2.20, 3.15), MTF+SU: 1.39 (1.12, 1.72) |
| Hung
et al.
(2013) 20 |
13238 | Veterans
Administration (US) |
1999–
2008 |
MTF, SU,
MTF+ SU |
Median (IQR)
MTF: 59 (54, 67) SU: 60 (54, 71) MTF+SU: 58 (53, 65) |
Serum
creatinine >1.5 mg/dL or eGFR < 60 |
eGFR Median (IQR)
MTF: 81 (72, 93) SU: 80 (71, 93) MTF+SU: 82 (73, 97) |
NR | Median (IQR)
MTF: 7.1 (6.5, 7.9) SU: 7.3 (6.6, 8.4) MTF+SU: 7.9 (6.8, 10) |
1 eGFR (≥25%
decline) 2 ESRD (eGFR<15, ICD-9 codes for dialysis or renal transplant) 3 Mortality |
Mean: 1.2 |
eGFR event
or ESRD Referent: SU MTF: 0.85 (0.72, 1.01), SU+MTF: 1.01 (0.75, 1.37) eGFR event, ESRD or mortality Referent: SU MTF: 0.82 (0.70, 0.97), SU+MTF 1.05 (0.79, 1.40) |
| Masica
et al.
(2013) 22 |
Proteinuria analysis:
N=798 eGFR analysis: N=977 [IPW cohort] |
Clinical data
from primary care networks (US) |
1998–
2009 |
Exposure to
drug (≥90d) MTF, SU, TZD, or combo |
Mean (SD)
MTF: 53.9 (11.9) SU: 53.7 (13.0) TZD: 53.9 (12.0) [Age at diagnosis, IPW cohort] |
Baseline
proteinuria or MDRD eGFR<60 |
eGFR Mean (SD)
Proteinuria analysis: MTF: 82.3 (20) SU: 79.5 (23) TZD: 75.6 (16) eGFR analysis: MTF: 86.8 (18) SU: 86.2 (21) TZD: 91.4 (34) |
NR | 8.0 % IPW
group |
1 New proteinuria
(24-hour albumin/protein, spot protein, spot ACR, or dipstick) 2 New eGFR <60 |
Proteinuria
analysis: Mean: 3.2 eGFR analysis: Mean: 2.8 |
9% (72/798)
developed proteinuria Incidence of proteinuria MTF referent SU: 1.27 (0.93, 1.74), TZD: 1.00 (0.70, 1.42) Fall in eGFR to <60 (2) MTF referent SU: 1.41 (1.05, 1.91), TZD: 1.04 (0.71, 1.50) |
| Hippisley-
Cox and Coupland (2016) 23 |
274,324
[N for kidney analysis not reported] |
QResearch (UK) | 2007 –
2015 |
DPP4i, TZD,
MTF, SU, ‘other agents’ |
Mean (SD)
TZD: 63 (12) DPP4I: 63 (12) MTF: 64 (13) SU: 66 (13) Other: 60 (12) |
Kidney
disease at baseline, and severe kidney disease |
NR for kidney
analysis: prior to kidney baseline exclusions: Creatinine µmol/L mean (SD) TZD: 87 (34), DPP4I: 85 (33), MTF: 85 (30), SU: 92 (48) |
% 1–3yrs
since diagnosis: TZD: 28 DPP4I: 26 MTF: 25 SU: 24 |
Mmol/mol
Mean (SD) TZD: 67 (19) DPP4i: 68 (18) MTF: 61 (19) SU: 65 (20) Other: 71 (20) |
Incident severe
kidney failure (Read codes for dialysis & transplantation, or CKD stage 5 based on serum creatinine values) |
NR |
Incident
severe kidney failure MTF referent TZD: 2.55 (1.13, 5.74), DPP4i: 3.52 (2.04, 6.07), SU: 2.63 (2.25, 3.06), MTF+SU: 0.76 (0.62, 0.92), MTF+TZD: 0.71 (0.33, 1.50), MTF+DPP4i: 0.59 (0.28, 1.25), SU+TZD: 2.14 (1.27, 3.61), SU+DPP4I: 3.21 (2.08, 4.93) |
| Kolaczynski
et al. (2016) 24 |
5436
matched sample |
IMS Lifelink
(Germany) |
2007–
2013 |
SU, DPP4i | Mean (SD)
SU: 63.7 (10.7) DPP4I: 64.6 (10.9) |
History of
nephropathy |
Renal failure %
(ICD-10 code) DPP4I: 13 SU: 11.1 |
Mean (SD)
DPP4I: 3.1 (3.4) SU: 3.2 (3.4) |
Mean (SD)
DPP4i: 7.61 (1.47), SU: 7.64 (1.37) |
Incident
nephropathy (ICD-10 code) |
Mean (SD)
DPP4I: 3.48 (3.75) SU: 2.49 (3.46) |
Incidence of
nephropathy Referent SU DPP4i 0.90 (0.72, 1.14) |
| Goldshtein
et al. (2016) 25 |
564
matched sample |
Maccabi
Health Service diabetes registry (Israel) |
2008–
2014 |
MTF+SU,
MTF+DPP4i |
Mean (SD)
SU: 58.5 (11) DPP4I: 59.1 (11.2) |
Dialysis,
eGFR <45 or ACE/ARB in 90 day post index |
ACR mg/g
mean (SD) SU: 122.4 (194.5) DPP4I: 139.9 (261.9) eGFR mean (SD) SU: 84 (19.5), DPP4I: 82.4 (19.1) |
Mean (SD)
SU: 5 (3.5), DPP4I: 5.2 (3.5) |
Mean (SD)
SU: 8.6 (1.5), DPP4i: 8.5 (1.5) |
Improvements
in urinary ACR (≥20% improvement in ACR and change in KDIGO category) |
Mean:
9 months, max 52 weeks |
ACR
reductions Referent MTF+SU MTF+DPP4i: 1.20 (0.99,1.47) |
| Carlson
et al. (2016) 26 |
168,443 | All Danish
citizens |
2000–
2012 |
MTF, SU | Mean (SD)
MTF: 65.7 (9.4) SU: 69.2 (10.8) |
ESRD or
eGFR <30 ml/min/1.73m 2 |
eGFR Median (IQR)
MTF: 74 (63–87) SU: 69 (57–82) |
NR | NR | 1 Acute dialysis | 1y
following treatment initiation |
Acute
dialysis Referent: SU MTF: 1.51 (1.06–2.17) |
Abbreviations: ACR: Albumin: Creatinine Ratio, eGFR: estimated glomerular filtration rate, ESRD: End Stage Renal Disease, ICD: International Classification of Diseases, MTF: metformin, SU: sulfonylurea, TZD: Thiazolidinedione, DPP4i: Dipeptidyl peptidase-4 inhibitor, RSG: Rosiglitazone, STG: Sitagliptin, EXE: Exenatide. IPW: Inverse Probability Weight, FU: Follow-up, SD: Standard deviation, ARF: Acute Renal Failure, CKD: Chronic Kidney Disease, IQR: Inter Quartile Range, p-yr: person-years, NR: Not reported, DB: Database, KDIGO: Kidney Disease: Improving Global Outcomes Notes: a: MACE: Major adverse cardiac event: non-fatal MI, non-fatal stroke, or cardiovascular death, b: microalbuminuria if ACR was >30 mg/g, c: Hazard Ratio (HR), Mantel Haenszel (MH) or Odds Ratio (OR), eGFR units: mL/min/1.73m 2