Initiating SGLT2 inhibitor therapy to improve renal outcomes for persons with diabetes eligible for an intensified glucose-lowering regimen: hypothetical intervention using parametric g-formula modeling.

Abstract

INTRODUCTION:

Sodium-glucose cotransporter 2 (SGLT2) inhibitors are now recommended in guidelines for persons with type 2 diabetes mellitus (T2DM) and at risk of advanced kidney disease as part of the glucose-lowering regimen.

RESEARCH DESIGN AND METHODS:

To explore the optimal threshold at which to initiate SGLT2 inhibitor therapy, we conducted an observational study analyzed under a counterfactual framework. This study used the electronic healthcare database in Japan, comprising data from approximately 20 million patients at approximately 160 medical institutions. Persons with T2DM with an estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73 m2 in April 2014 were eligible. The primary end point was the composite of renal deterioration (>40% decline in eGFR) and the development of eGFR<30 mL/min/1.73 m2. We estimated the risk of the composite end point occurring over 77 months in different scenarios, such as early or delayed intervention with SGLT2 inhibitors for uncontrolled diabetes at different hemoglobin A1c (HbA1c) thresholds. The parametric g-formula was used to estimate the risk of the composite end point, adjusting for time-fixed and time-varying confounders.

RESULTS:

We analyzed data from 36 237 persons (149 346 person-years observation), of whom 4679 started SGLT2 inhibitor therapy (9470 person-years observation). Overall, initiating SGLT2 inhibitor therapy was associated with a 77-month risk reduction in the end point by 1.3-3.7%. The largest risk reduction was observed within 3 months of initiation once the HbA1c level exceeded 6.5% (risk reduction of 3.7% (95% CI 1.6% to 6.7%)) compared with a threshold of 7.0% or higher.

CONCLUSIONS:

Our analyses favored early intervention with SGLT2 inhibitors to reduce the renal end point, even for persons with moderately controlled HbA1c levels. Our findings also suggest caution against clinical inertia in the care of diabetes.

• Authors: Masato Takeuchi, Masahito Ogura, Nobuya Inagaki, Koji Kawakami
• Journal: BMJ open diabetes research & care (BMJ Open Diabetes Res Care) Vol. 10 Issue 3 (06 2022) ISSN: 2052-4897 [Electronic] England
• PMID: 35675951 (Publication Type: Journal Article, Observational Study, Research Support, Non-U.S. Gov't)
• Copyright: © Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Chemical References

• Glycated Hemoglobin A
• Sodium-Glucose Transporter 2 Inhibitors
• Glucose

Topics

• Diabetes Mellitus, Type 2 (drug therapy)
• Glomerular Filtration Rate
• Glucose
• Glycated Hemoglobin
• Humans
• Sodium-Glucose Transporter 2 Inhibitors (therapeutic use)