Table 2.
Glycemic efficacy of incretin-based therapies and SGLT2 inhibitors in patients with CKD.
|
Intervention
(N Randomized) |
Duration
(Weeks) |
Background
Therapy |
Baseline CKD Staging
(eGFR, mL/min/1.73 m2) |
HbA1c, mmol/mol (%) | ||
|---|---|---|---|---|---|---|
| Baseline | Adjusted Mean Change from Baseline | Difference vs Comparator | ||||
| Linagliptin 5 mg (68) Placebo (65) [23] |
52 | Other antidiabetes drugs, including insulin | 4/5 (<30)* | 66 (8.2) 66 (8.2) |
−8 (−0.7) 0 (0.0) |
−8 (−0.7) – |
| Linagliptin 5 mg (113) Placebo /glimepiride†(122) [24] |
52 | Insulin ± other OADs | ≥3 (<60) | 65 (8.1)‡ | −7 (−0.6) −6 (−0.5) |
NR – |
| Sitagliptin 50§or 25ǁ mg (65) Placebo/glipizide¶ (26) [27] |
54 | Insulin monotherapy (no other OADS) | Moderate§ to Severeǁ including ESRD | 60 (7.6) 62 (7.8) |
−8 (−0.7) −9 (−0.8) |
NR – |
| Sitagliptin 25 mg (64) Glipizide** (65) [28] |
54 | None | ESRD on dialysis | 63 (7.9) 62 (7.8) |
−8 (−0.7) −10 (−0.9) |
2 (0.2) – |
| Saxagliptin 2.5 mg (85) Placebo (85) [31] |
52 | Other antidiabetes drugs, including insulin | Moderateǁ to Severe¶
including ESRD |
68 (8.4) 65 (8.1) |
−12 (−1.1) −4 (−0.4) |
−8 (−0.7) – |
| Liraglutide 1.8 mg (140) Placebo (137) [NCT01620489] |
26 | Other OADs ± insulin | 3 (≥30 to <60) | 65 (8.1) 64 (8.0) |
−12 (−1.1) −4 (−0.4) |
−8 (−0.7) – |
| Albiglutide 30 mg (254)†† Sitagliptin (253)[40]†† |
26 | Other OADs‡‡ | Mild (≥60 to ≤89) Moderate (≥30 to ≤59) Severe (≥15 to ≤29) |
65 (8.1) 66 (8.2) |
−9 (−0.8) −6 (−0.5) |
−3 (−0.3) |
| Empagliflozin 25 mg (97/188/37)§§
Placebo (97/187/37) [46] |
24 | Other antidiabetes drugs, including insulin |
2 (≥60 to <90) | 64 (8.0) 65 (8.1) |
−7 (−0.6) 1 (0.1) |
−8 (−0.7) – |
| 3 (≥30 to <60) | 64 (8.0) 65 (8.1) |
−3 (−0.3) 1 (0.1) |
−4 (−0.4) – |
|||
| 4 (≥15 to <30) | 65 (8.1) 66 (8.2) |
1 (0.1) −4 (−0.4) |
NR – |
|||
| Canagliflozin 100 mg (90)ǁǁ Canagliflozin 300 mg (89)ǁǁ Placebo (90) [51]ǁǁ |
26 | None or other antidiabetes, therapies including insulin and GLP-1 analogs |
3 (≥30 to <50) | 63 (7.9) 64 (8.0) 64 (8.0) |
−3 (−0.3) −4 (−0.4) 0 (0.0) |
−3 (−0.3) −4 (−0.4) – |
*14.5% (19/133) of all randomized patients had baseline eGFR of 30 to 60 mL/min/1.73m2.
†Placebo for 12 weeks followed by glimepiride (1–4 mg/day) for 40 weeks.
‡Overall mean baseline value.
§CrCl ≥30 to <50 mL/min.
ǁCrCl <30 mL/min
¶ Placebo for 12 weeks followed by glipizide for 42 weeks.
**2.5 mg/day titrated to 10 mg twice daily.
††Albiglutide: initial dose 30 mg/week uptitrated to 50 mg/week as needed. Sitagliptin: 100 mg (mild CKD), 50 mg (moderate CKD), 25 mg (severe CKD).
‡‡ Patients with eGFR <60 mL/min/1.73m2 were washed off metformin therapy.
§§Stage 2 CKD patients were randomized to empagliflozin 10 mg, 25 mg or placebo, data for the 10 mg arm are not shown. The n values represent number of patients in each treatment group with stage 2/stage 3/stage 4 CKD.
ǁǁ Number of patients who received the study drug.
CKD, chronic kidney disease; ESRD, end-stage renal disease, GLP-1, glucagon-like peptide 1; NR, not reported; OAD, oral antidiabetes drug; SGLT2, sodium glucose co-transporter 2; CrCl, creatinine clearance; eGFR, estimated glomerular filtration rate.