Table 3.
Summary of evidence for treatment effect heterogeneity for SGLT2-inhibitor and GLP1-receptor agonist therapies for renal outcomes.
| GLP1-RA | SGLT2i | Plain language summary | |||||
|---|---|---|---|---|---|---|---|
| Renal (eGFR changes/CKD progression/composite outcomes of these with or without ACR changes) | GRADE EVIDENCE B | GRADE EVIDENCE B | |||||
| Biomarker | N (observational) |
N (RCT) |
N (Meta-analysis and pooled RCT) |
N (observational) |
N (RCT) |
N (Meta-analysis and pooled RCT) |
|
| Baseline HbA1c | 0 | 0 | 0 | 0 | 0 | 0 | |
| Renal Function | 0 | 3122,127,128 | 15 | 2129,130 | 6114,115,117–119,127 | 52,82,111–113 | Generally no relationship between either eGFR or ACR and GLP1-RA benefit. Greater relative benefit of SGLT2i in those with higher eGFR (although inconsistent results with some studies showing no impact and 1 observational study finding the opposite relationship). Generally no relationship between ACR/proteinuria and SGLT2i benefit. |
| BMI | 0 | 2122,126 | 0 | 1129 | 287,184 | 179 | Greater GLP1-RA benefit with lower BMI but not seen consistently. Generally no effect on SGLT2i benefit |
| Age | 0 | 1121 | 0 | 2129,130 | 0 | 179 | No effect on GLP1-RA or SGLT2i benefit |
| Diabetes duration | 0 | 1124 | 0 | 0 | 0 | 179 | No effect on GLP1-RA or SGLT2i benefit |
| Sex | 0 | 0 | 0 | 1129 | 1173 | 179 | No effect on SGLT2i benefit |
| Ethnicity | 0 | 0 | 0 | 0 | 2184,189 | 179 | No effect on SGLT2i benefit |
| Genetics | 0 | 0 | 0 | 0 | 0 | 0 | |
| Non-routine biomarkers | 0 | 0 | 0 | 0 | 589,120,178–180 | 0 | No effect on SGLT2i benefit |
| Blood pressure/hypertension | 0 | 2122,123 | 0 | 1129 | 0 | 179 | No effect on GLP1-RA or SGLT2i benefit |
| History of CVD/HF | 0 | 2122,125 | 0 | 1129 | 3168,169,190 | 32,80,112 | No effect on GLP1-RA or SGLT2i benefit |
| Renal (albuminuria changes) | GRADE EVIDENCE B | GRADE EVIDENCE B | |||||
| Baseline HbA1c | 0 | 0 | 0 | 0 | 0 | 0 | |
| Renal Function | 0 | 2122,128 | 15 | 0 | 0 | 1113 | Greater GLP1-RA benefit with higher ACR although not seen consistently. No relationship between eGFR and GLP1-RA. No effect on SGLT2i benefit |
| BMI | 0 | 1122 | 0 | 0 | 0 | 0 | No effect on GLP1-RA benefit |
| Age | 0 | 0 | 0 | 0 | 0 | 0 | |
| Diabetes duration | 0 | 0 | 0 | 0 | 0 | 0 | |
| Sex | 0 | 0 | 0 | 0 | 0 | 0 | |
| Ethnicity | 0 | 0 | 0 | 0 | 1189 | 0 | No effect on SGLT2i benefit |
| Genetics | 0 | 0 | 0 | 0 | 0 | 0 | |
| Non-routine biomarkers | 0 | 0 | 0 | 0 | 1120 | 0 | Single trial found greater SGLT2i benefit at higher IGFBP7 |
| Blood pressure/hypertension | 0 | 1122 | 0 | 0 | 0 | 0 | No effect on GLP1-RA benefit |
| History of CVD/HF | 0 | 1122 | 0 | 0 | 0 | 0 | No effect on GLP1-RA benefit |