Table 5.
Kidney outcomes in clinical trials of newer antihyperglycemic therapies
| Name of the Study | Tested Intervention/Drugs | Study Population | Outcomes |
| SAVOR-TIMI (84) | Saxagliptin (DPP-4 inhibitor) | DM2, HbA1c≥6.5%, high risk for CV events | Improvement in and/or less deterioration in ACR categories from baseline to end of trial (P=0.02, P<0.001, and P=0.05 for normoalbuminuria, microalbuminuria, and macroalbuminuria, respectively); no changes in eGFR |
| CARMELINA (85) | Linagliptin (DPP-4 inhibitor) | DM2, 6.5%≥HbA1c≤10%, albuminuria, macrovascualar complications, eGFR>15 ml/min per 1.73 m2 | In progress, estimated completion in January of 2018 |
| LEADER (75) | Liraglutide (GLP-1 receptor agonist) | DM2, HbA1c>7%, eGFR<60 ml/min per 1.73 m2, CV coexisting disease | Lower incidence of nephropathy (new-onset albuminuria, doubling of SCr and CrCl<45 ml/min per 1.73 m2; need for RRT, death to renal causes [1.5 number of events per 100 patients per year versus 1.9 number of events per 100 patients per year; P=0.003]) |
| AWARD-7, (86) | Dulaglutide (GLP-1 receptor agonist) | DM2, 7.5%≥HbA1c≤10.5%, 15≥eGFR≤60 ml/min per 1.73 m2 | In progress, estimated completion in July of 2018 |
| EMPA-REG OUTCOME (78) | Empaglifozin (SGLT-2 inhibitor) | DM2, eGFR≥30 ml/min per 1.73 m2, high CV risk | 44% Relative risk reduction of doubling of SCr (1.5% versus 2.6%); 38% relative risk reduction of progression to macroalbuminuria (11.2% versus 16.2%); 55% relative risk reduction of initiation of RRT (0.3% versus 0.6%); slowing GFR decline (annual decrease 0.19±0.11 versus 1.67±0.13 ml/min per 1.73 m2; P<0.001) |
| CREDENCE (87) | Canaglifozin (SGLT-2 inhibitor) | DM2, 6.5%≥HbA1c≤12%, high CV risk, 300 mg/g≥UACR≤5000 mg/g, 30≥eGFR≤90 ml/min per 1.73 m2 | In progress, estimated completion in June of 2019 |
eGFR is in milliliters per minute per 1.73 m2. UACR is in milligrams per gram. SAVOR-TIMI, Does Saxagliptin Reduce the Risk of Cardiovascular Events When Used Alone or Added to Other Diabetes Medications; DPP-4, dipeptidyl peptidase-4 inhibitor; DM2, diabetes mellitus type 2; HbA1c, hemoglobin A1c; CV, cardiovascular; ACR, albumin-to-creatinine ratio; CARMELINA, Cardiovascular and Renal Microvascular Outcome Study With Linagliptin in Patients With Type 2 Diabetes Mellitus; LEADER, Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results; GLP-1, glucagon-like peptide-1; SCr, serum creatinine; CrCl, creatinine clearance; AWARD-7, A Study Comparing Dulaglutide With Insulin Glargine on Glycemic Control in Participants With Type 2 Diabetes (T2D) and Moderate or Severe Chronic Kidney Disease (CKD); EMPA-REG OUTCOME, Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients; SGLT-2, sodium-glucose cotransporter 2; CREDENCE, Evaluation of the Effects of Canagliflozin on Renal and Cardiovascular Outcomes in Participants with Diabetic Nephropathy; UACR, urine albumin-to-creatinine ratio.