Sodium-glucose cotransporter 2 inhibitor-induced reduction in the mean arterial pressure improved renal composite outcomes in type 2 diabetes mellitus patients with chronic kidney disease: A propensity score-matched model analysis in Japan

J Diabetes Investig. 2021 Aug;12(8):1408-1416. doi: 10.1111/jdi.13491. Epub 2021 Feb 1.

Abstract

Aims/introduction: Large-scale clinical trials have reported that, in patients with type 2 diabetes mellitus, sodium-glucose cotransporter 2 (SGLT2) inhibitor treatment affords favorable renal outcomes; the underlying mechanisms, however, remain unclear. Thus, this study investigated how SGLT2 inhibitor-induced changes in the mean arterial pressure (MAP; denoted as ΔMAP) are associated with renal outcomes in type 2 diabetes mellitus patients with chronic kidney disease (CKD).

Materials and methods: We retrospectively assessed the data of 624 Japanese type 2 diabetes mellitus patients with CKD who had been using SGLT2 inhibitors for >1 year. For propensity score matching (1:1 nearest neighbor match, with caliper value = 0.053, no replacement), patients were categorized into two groups based on the ΔMAP (>-4 mmHg [n = 329] and ≤-4.0 mmHg [n = 295]). Composite albuminuria progression or a ≥15% annual reduction in the estimated glomerular filtration rate was regarded as the end-point.

Results: Per group, 173 propensity-matched patients were compared. Patients with ΔMAP ≤-4 mmHg had a significantly lower incidence of composite renal outcomes than those with ΔMAP ≥-4 mmHg (5.8% [n = 10] vs 15.6% [n = 27], P = 0.003). Although the between-group differences in the estimated glomerular filtration rates were non-significant, patients with a ΔMAP ≤-4 mmHg had significantly larger reductions in the logarithmic urine albumin-to-creatinine ratio (P = 0.005).

Conclusions: The degree of blood pressure reduction after SGLT2 inhibitor treatment influenced renal composite outcomes in Japanese type 2 diabetes mellitus patients with CKD, confirming the importance of blood pressure management in type 2 diabetes mellitus patients with CKD, even when they are under SGLT2 inhibitor treatment.

Keywords: Blood pressure; Chronic kidney disease; Sodium-glucose cotransporter 2 inhibitors.

MeSH terms

  • Aged
  • Arterial Pressure / drug effects*
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetic Nephropathies
  • Female
  • Glomerular Filtration Rate
  • Humans
  • Hypoglycemic Agents / therapeutic use*
  • Japan
  • Kidney Function Tests
  • Male
  • Middle Aged
  • Models, Statistical
  • Propensity Score
  • Renal Insufficiency, Chronic / complications
  • Renal Insufficiency, Chronic / drug therapy*
  • Retrospective Studies
  • Sodium-Glucose Transporter 2 Inhibitors / therapeutic use*
  • Treatment Outcome

Substances

  • Hypoglycemic Agents
  • Sodium-Glucose Transporter 2 Inhibitors