Comparative efficacy of novel antidiabetic drugs on cardiovascular and renal outcomes in patients with diabetic kidney disease: A systematic review and network meta-analysis

Abstract

Aims: To conduct a systematic review and network meta-analysis to determine the comparative effectiveness of sodium-glucose cotransporter-2 (SGLT2) inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1RAs) and dipeptidyl peptidase-4 (DPP-4) inhibitors in patients with diabetic kidney disease (DKD).

Methods: Phase III or IV randomized, placebo-controlled trials evaluating SGLT2 inhibitors, GLP-1RAs or DPP-4 inhibitors in patients with DKD were identified from the MEDLINE database. The outcomes of interest were a kidney-specific composite outcome, kidney disease progression, major adverse cardiovascular events (MACE), hospitalization for heart failure (HHF) and cardiovascular death. A network meta-analysis was conducted to calculate hazard ratios (HRs) and 95% confidence intervals (CIs).

Results: Sixteen trials representing a total of 46 292 patients were included. SGLT2 inhibitors significantly reduced the risk of the kidney-specific composite outcome by 26% compared to GLP-1RAs (HR 0.74, 95% CI 0.62-0.88) and by 36% compared to DPP-4 inhibitors (HR 0.64, 95% CI 0.52-0.79). The risk of MACE was significantly reduced with SGLT2 inhibitors (by 18%; HR 0.82, 95% CI 0.72-0.93), and with GLP-1RAs (by 18%; HR 0.82, 95% CI 0.69-0.96), compared to DPP-4 inhibitors. SGLT2 inhibitors significantly reduced the risk of HHF by 28% compared to GLP-1RAs (HR 0.72, 95% CI 0.56-0.92) and by 41% compared to DPP-4 inhibitors (HR 0.59, 95% CI 0.49-0.71).

Conclusions: A clear advantage was demonstrated by SGLT2 inhibitors in reducing the risks of CV and renal events in patients with DKD, compared to GLP-1RAs and DPP-4 inhibitors. We recommend that SGLT2 inhibitors be considered the treatment of choice in patients with DKD.

Keywords: diabetic kidney disease; dipeptidyl peptidase-4 inhibitors; glucagon-like peptide-1 receptor agonists; network meta-analysis; sodium-glucose cotransporter-2 inhibitors.

FIGURE 1

Overall network profile. This network meta‐analysis included four studies that evaluated dipeptidyl peptidase‐4 (DPP‐4) inhibitors, five that evaluated glucagon‐like peptide‐1 receptor agonists (GLP‐1Ras) and seven that evaluated sodium‐glucose cotransporter‐2 (SGLT2) inhibitors

FIGURE 2

Risk of renal and cardiovascular (CV) outcomes with different antidiabetic drug classes. Forest plots comparing the risks of (A) kidney‐specific outcome, (B) major adverse cardiovascular events (MACE), (C) cardiovascular (CV) death and (D) hospitalization for heart failure (HHF) with different antidiabetic drug classes compared to placebo. DPP‐4, dipeptidyl peptidase‐4; GLP‐1RA, glucagon‐like peptide‐1 receptor agonist; SGLT2, sodium‐glucose cotransporter‐2

FIGURE 3

Comparison between treatments for (A) kidney‐specific composite outcome, (B) major adverse cardiovascular events (MACE), (C) cardiovascular (CV) death and (D) hospitalization for heart failure (HHF). DPP‐4, dipeptidyl peptidase‐4; GLP‐1RA, glucagon‐like peptide‐1 receptor agonist; SGLT2, sodium‐glucose cotransporter‐2 inhibitor