PMID- 35675951 OWN - NLM STAT- MEDLINE DCOM- 20220610 LR - 20221207 IS - 2052-4897 (Electronic) IS - 2052-4897 (Linking) VI - 10 IP - 3 DP - 2022 Jun TI - 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. LID - 10.1136/bmjdrc-2021-002636 [doi] LID - e002636 AB - 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 m(2) 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 m(2). 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 (HbA(1c)) 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 HbA(1c) 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 HbA(1c) levels. Our findings also suggest caution against clinical inertia in the care of diabetes. CI - (c) 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. FAU - Takeuchi, Masato AU - Takeuchi M AUID- ORCID: 0000-0002-2990-2687 AD - Department of Pharmacoepidemiology, Graduate School of Medicine and Public Health, Kyoto University, Kyoto, Japan takeuchi.masato.3c@kyoto-u.ac.jp. FAU - Ogura, Masahito AU - Ogura M AD - Department of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, Japan. FAU - Inagaki, Nobuya AU - Inagaki N AUID- ORCID: 0000-0001-8261-2593 AD - Department of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, Japan. FAU - Kawakami, Koji AU - Kawakami K AD - Department of Pharmacoepidemiology, Graduate School of Medicine and Public Health, Kyoto University, Kyoto, Japan. LA - eng PT - Journal Article PT - Observational Study PT - Research Support, Non-U.S. Gov't PL - England TA - BMJ Open Diabetes Res Care JT - BMJ open diabetes research & care JID - 101641391 RN - 0 (Glycated Hemoglobin A) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - IY9XDZ35W2 (Glucose) SB - IM MH - *Diabetes Mellitus, Type 2/drug therapy MH - Glomerular Filtration Rate MH - Glucose MH - Glycated Hemoglobin MH - Humans MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use PMC - PMC9185419 OTO - NOTNLM OT - Nephrology OT - Pharmacoepidemiology COIS- Competing interests: MT received a consultation fee from Eisai Co., Ltd. MO received research support from Takeda Pharmaceutical Co., Ltd. and speaker honoraria from Takeda Pharmaceutical Co., Ltd., Nippon Boehringer Ingelheim Co., Ltd., Daiichi Sankyo Co., Ltd., Ono Pharmaceutical Co., Ltd, AstraZeneca, MSD K.K., Novo Nordisk Pharma Ltd., Eli Lilly Japan K.K., Sanofi K.K., Mitsubishi Tanabe Pharma Co., Kyowa Hakko Kirin Co., Ltd, Kowa Co., Ltd., Astellas Pharma Inc., Sumitomo Dainippon Pharma Co., Ltd., and Taisho Toyama Pharmaceutical. NI received research funds from Terumo Corp., Drawbridge, Inc., and asken Inc; speaker honoraria from Kowa Co., Ltd., MSD K.K., Astellas Pharma Inc., Novo Nordisk Pharma Ltd., Ono Pharmaceutical Co., Ltd., Nippon Boehringer Ingelheim Co., Ltd., Takeda Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Corp., Sumitomo Dainippon Pharma Co., Ltd., Sanofi K.K., Eli Lilly Japan K.K.; and scholarship grants from Kissei Pharmaceutical Co., Ltd., Sanofi K.K., Daiichi-Sankyo Co., Ltd., Mitsubishi Tanabe Pharma Corp., Takeda Pharmaceutical Co., Ltd., Japan Tobacco Inc., Kyowa Kirin Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd., Astellas Pharma Inc., MSD K.K., Ono Pharmaceutical Co., Ltd., Sanwa Kagaku Kenkyusho Co., Ltd., Nippon Boehringer Ingelheim Co., Ltd., Novo Nordisk Pharma Ltd., Novartis Pharma K.K., and Life Scan Japan K.K. KK received research funds from Eisai Co., Ltd., Kyowa Kirin Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd., Pfizer Inc., Stella Pharma Corporation, CMIC Co., Ltd., Suntory Beverage & Food Ltd., Mitsubishi Corporation, and Real World Data Co., Ltd.; consulting fees from LEBER Inc., JMDC Inc., Shin Nippon Biomedical Laboratories Ltd., Kaken Pharmaceutical Co., Ltd., and Advanced Medical Care Inc.; executive compensation from Cancer Intelligence Care Systems Inc.; and honoraria from Mitsubishi Chemical Holdings Corporation, Mitsubishi Corporation, and Pharma Business Academy; and holds stock in Real World Data Co., Ltd. KK declares no competing interests. EDAT- 2022/06/09 06:00 MHDA- 2022/06/11 06:00 PMCR- 2022/06/08 CRDT- 2022/06/08 20:52 PHST- 2021/10/12 00:00 [received] PHST- 2022/05/24 00:00 [accepted] PHST- 2022/06/08 20:52 [entrez] PHST- 2022/06/09 06:00 [pubmed] PHST- 2022/06/11 06:00 [medline] PHST- 2022/06/08 00:00 [pmc-release] AID - 10/3/e002636 [pii] AID - bmjdrc-2021-002636 [pii] AID - 10.1136/bmjdrc-2021-002636 [doi] PST - ppublish SO - BMJ Open Diabetes Res Care. 2022 Jun;10(3):e002636. doi: 10.1136/bmjdrc-2021-002636.