Chronic kidney outcomes associated with GLP-1 receptor agonists versus long-acting insulins among type 2 diabetes patients requiring intensive glycemic control: a nationwide cohort study

Cardiovasc Diabetol. 2023 Oct 4;22(1):272. doi: 10.1186/s12933-023-01991-5.

Abstract

Background: Effectiveness of glucagon-like peptide-1 receptor agonists (GLP-1RAs) versus long-acting insulins (LAIs) on preventing progressive chronic kidney outcomes is uncertain for type 2 diabetes (T2D) patients requiring intensive glycemic control. This study aimed to evaluate comparative effectiveness of GLP-1RA versus LAI therapies on progressive chronic kidney outcomes among patients having poor glycemic control and requiring these injectable glucose-lowering agents (GLAs).

Methods: 7279 propensity-score-matched pairs of newly stable GLP-1RA and LAI users in 2013-2018 were identified from Taiwan's National Health Insurance Research Database and followed until death or 12/31/2019 (intention-to-treat). Subdistributional hazard model was utilized to assess the comparative effectiveness on a composite renal outcome (i.e., renal insufficiency [eGFR < 15 mL/min/1.73 m2], dialysis-dependent end-stage renal disease [ESRD], or renal death) and its individual components. Sensitivity analyses with the as-treated scenario, PS weighting, high-dimensional PS techniques, using cardiovascular diseases (CVDs) as positive control outcomes, and interaction testing were performed.

Results: In primary analyses, subdistribution hazard ratios (95% CIs) for initiating GLP-1RAs versus LAIs for the composite renal outcome, renal insufficiency, dialysis-dependent ESRD, and renal death were 0.39 (0.30-0.51), 0.43 (0.32-0.57), 0.29 (0.20-0.43), and 0.28 (0.15-0.51), respectively. Sensitivity analysis results were consistent with the primary findings. CVD history and the medication possession ratio of prior oral GLAs possessed modification effects on GLP-1RA-associated kidney outcomes.

Conclusion: Using GLP-1RAs versus LAIs was associated with kidney benefits in T2D patients requiring intensive glycemic control and potentially at high risk of kidney progression. GLP-1RAs should be prioritized to patients with CVDs or adherence to prior oral GLAs to maximize kidney benefits.

Keywords: Chronic kidney outcomes; GLP-1 receptor agonists; Intensive glycemic control; Long-acting insulins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cardiovascular Diseases* / prevention & control
  • Cohort Studies
  • Diabetes Mellitus, Type 2* / chemically induced
  • Diabetes Mellitus, Type 2* / diagnosis
  • Diabetes Mellitus, Type 2* / drug therapy
  • Glucagon-Like Peptide-1 Receptor / agonists
  • Humans
  • Hypoglycemic Agents / adverse effects
  • Insulin, Long-Acting / therapeutic use
  • Kidney
  • Kidney Failure, Chronic* / diagnosis
  • Kidney Failure, Chronic* / epidemiology
  • Renal Insufficiency*

Substances

  • Hypoglycemic Agents
  • Glucagon-Like Peptide-1 Receptor
  • Insulin, Long-Acting