Association between use of sodium-glucose cotransporter 2 inhibitors, glucagon-like peptide 1 agonists, and dipeptidyl peptidase 4 inhibitors with kidney outcomes in patients with type 2 diabetes: A systematic review and network meta-analysis.
Level 1 - systematic review of randomized trials
Systematic review and network meta-analysis of randomized controlled trials
PubMed 35421174 · doi:10.1371/journal.pone.0267025
What was done
A systematic review and Bayesian network meta-analysis searched PubMed, EMBASE, and CENTRAL through September 28, 2020 for randomized clinical trials in patients with type 2 diabetes. The study compared sodium-glucose cotransporter 2 (SGLT-2) inhibitors, glucagon-like peptide 1 (GLP-1) agonists, and dipeptidyl peptidase 4 (DPP-4) inhibitors against each other, placebo, or no treatment. The primary outcome was composite renal events, and the secondary outcome was acute kidney injury (AKI) events (PROSPERO CRD42020208090).
What was found
Across 98 included articles covering 186,335 participants, there was no statistically significant difference between drug classes for composite renal events, though GLP-1 agonists had an 80% probability of ranking best (moderate-quality evidence). For AKI, SGLT-2 inhibitors significantly reduced risk compared to controls (OR 0.74, 95% CI 0.62 to 0.87; low-quality evidence), GLP-1 agonists (OR 0.76, 95% CI 0.59 to 0.96; moderate-quality evidence), and DPP-4 inhibitors (OR 0.67, 95% CI 0.50 to 0.86; low-quality evidence).
Why it matters
This analysis clarifies the relative renal safety profiles of modern second-line antidiabetic agents, demonstrating that SGLT-2 inhibitors offer superior protection specifically against acute kidney injury events compared to GLP-1 agonists and DPP-4 inhibitors.
Limits
The evidence certainty was rated low to moderate across comparisons, driven by heterogeneity or imprecision in the underlying trial network. The literature search ended in September 2020, missing more recent large-scale cardiovascular and renal outcome trials. Specific diagnostic criteria for composite renal events and variations in baseline renal function across trials were not detailed in the abstract.
Cited by
- contradicts GLP-1 receptor agonist drugs carry an increased, though low, risk of kidney issues and blindness.