Canagliflozin Slows Progression of Renal Function Decline Independently of Glycemic Effects - PubMed (original) (raw)
Randomized Controlled Trial
. 2017 Jan;28(1):368-375.
doi: 10.1681/ASN.2016030278. Epub 2016 Aug 18.
Affiliations
- PMID: 27539604
- PMCID: PMC5198289
- DOI: 10.1681/ASN.2016030278
Randomized Controlled Trial
Canagliflozin Slows Progression of Renal Function Decline Independently of Glycemic Effects
Hiddo J L Heerspink et al. J Am Soc Nephrol. 2017 Jan.
Abstract
Sodium-glucose cotransporter 2 inhibition with canagliflozin decreases HbA1c, body weight, BP, and albuminuria, implying that canagliflozin confers renoprotection. We determined whether canagliflozin decreases albuminuria and reduces renal function decline independently of its glycemic effects in a secondary analysis of a clinical trial in 1450 patients with type 2 diabetes receiving metformin and randomly assigned to either once-daily canagliflozin 100 mg, canagliflozin 300 mg, or glimepiride uptitrated to 6-8 mg. End points were annual change in eGFR and albuminuria over 2 years of follow-up. Glimepiride, canagliflozin 100 mg, and canagliflozin 300 mg groups had eGFR declines of 3.3 ml/min per 1.73 m2 per year (95% confidence interval [95% CI], 2.8 to 3.8), 0.5 ml/min per 1.73 m2 per year (95% CI, 0.0 to 1.0), and 0.9 ml/min per 1.73 m2 per year (95% CI, 0.4 to 1.4), respectively (P<0.01 for each canagliflozin group versus glimepiride). In the subgroup of patients with baseline urinary albumin-to-creatinine ratio ≥30 mg/g, urinary albumin-to-creatinine ratio decreased more with canagliflozin 100 mg (31.7%; 95% CI, 8.6% to 48.9%; P=0.01) or canagliflozin 300 mg (49.3%; 95% CI, 31.9% to 62.2%; P<0.001) than with glimepiride. Patients receiving glimepiride, canagliflozin 100 mg, or canagliflozin 300 mg had reductions in HbA1c of 0.81%, 0.82%, and 0.93%, respectively, at 1 year and 0.55%, 0.65%, and 0.74%, respectively, at 2 years. In conclusion, canagliflozin 100 or 300 mg/d, compared with glimepiride, slowed the progression of renal disease over 2 years in patients with type 2 diabetes, and canagliflozin may confer renoprotective effects independently of its glycemic effects.
Keywords: SGLT2; canagliflozin; diabetic nephropathy; renal function.
Copyright © 2016 by the American Society of Nephrology.
Figures
Figure 1.
Canagliflozin slows the progression of eGFR decline in patients with type 2 diabetes compared with glimepiride. (A) Changes in eGFR in the canagliflozin and glimepiride treatment arms in the overall population, and the rate of eGFR decline per year. (B) Changes in eGFR in the canagliflozin and glimepiride treatment arms in patients with UACR≥30 mg/g, and the rate of eGFR decline per year in patients with UACR≥30 mg/g.
Figure 2.
eGFR decline >30% or >40% was generally less frequent with canagliflozin compared with glimepiride.
Figure 3.
Canagliflozin decreases albuminuria compared with glimepiride. (A) Changes in UACR in the canagliflozin and glimepiride treatment arms in the overall population. (B) Changes in UACR in the canagliflozin and glimepiride treatment arms in a subgroup of patients with UACR≥30 mg/g at baseline.
Comment in
- SGLT2 Inhibitors-Sweet Success for Diabetic Kidney Disease?
de Boer IH, Kahn SE. de Boer IH, et al. J Am Soc Nephrol. 2017 Jan;28(1):7-10. doi: 10.1681/ASN.2016060650. Epub 2016 Aug 18. J Am Soc Nephrol. 2017. PMID: 27539605 Free PMC article. No abstract available.
Similar articles
- Glycemic Control and Effects of Canagliflozin in Reducing Albuminuria and eGFR: A Post Hoc Analysis of the CREDENCE Trial.
van der Hoek S, Jongs N, Oshima M, Neuen BL, Stevens J, Perkovic V, Levin A, Mahaffey KW, Pollock C, Greene T, Wheeler DC, Jardine MJ, Heerspink HJL. van der Hoek S, et al. Clin J Am Soc Nephrol. 2023 Jun 1;18(6):748-758. doi: 10.2215/CJN.0000000000000161. Epub 2023 Mar 31. Clin J Am Soc Nephrol. 2023. PMID: 36999981 Free PMC article. Clinical Trial. - Early Change in Albuminuria with Canagliflozin Predicts Kidney and Cardiovascular Outcomes: A Post Hoc Analysis from the CREDENCE Trial.
Oshima M, Neuen BL, Li J, Perkovic V, Charytan DM, de Zeeuw D, Edwards R, Greene T, Levin A, Mahaffey KW, De Nicola L, Pollock C, Rosenthal N, Wheeler DC, Jardine MJ, Heerspink HJL. Oshima M, et al. J Am Soc Nephrol. 2020 Dec;31(12):2925-2936. doi: 10.1681/ASN.2020050723. Epub 2020 Sep 30. J Am Soc Nephrol. 2020. PMID: 32998938 Free PMC article. Clinical Trial. - Efficacy and safety of canagliflozin versus glimepiride in patients with type 2 diabetes inadequately controlled with metformin (CANTATA-SU): 52 week results from a randomised, double-blind, phase 3 non-inferiority trial.
Cefalu WT, Leiter LA, Yoon KH, Arias P, Niskanen L, Xie J, Balis DA, Canovatchel W, Meininger G. Cefalu WT, et al. Lancet. 2013 Sep 14;382(9896):941-50. doi: 10.1016/S0140-6736(13)60683-2. Epub 2013 Jul 12. Lancet. 2013. PMID: 23850055 Clinical Trial. - The kidney and type 2 diabetes mellitus: therapeutic implications of SGLT2 inhibitors.
Weir MR. Weir MR. Postgrad Med. 2016;128(3):290-8. doi: 10.1080/00325481.2016.1147926. Epub 2016 Feb 19. Postgrad Med. 2016. PMID: 26821720 Review. - Renal protection by sodium-glucose cotransporter 2 inhibitors and its underlying mechanisms in diabetic kidney disease.
Mima A. Mima A. J Diabetes Complications. 2018 Jul;32(7):720-725. doi: 10.1016/j.jdiacomp.2018.04.011. Epub 2018 May 5. J Diabetes Complications. 2018. PMID: 29880432 Review.
Cited by
- Empagliflozin's role in early tubular protection for type 2 diabetes patients.
Zhang C, Ren W, Lu X, Feng L, Li J, Zhu B. Zhang C, et al. Mol Med. 2024 Jul 31;30(1):112. doi: 10.1186/s10020-024-00881-0. Mol Med. 2024. PMID: 39085830 Free PMC article. Clinical Trial. - Role of Estimated Glomerular Filtration Rate in Clinical Research: The Never-Ending Matter.
Abenavoli C, Provenzano M, Ksiazek SH, Hu L, Cuna V, Manna G, Comai G, Baraldi O. Abenavoli C, et al. Rev Cardiovasc Med. 2024 Jan 4;25(1):1. doi: 10.31083/j.rcm2501001. eCollection 2024 Jan. Rev Cardiovasc Med. 2024. PMID: 39077647 Free PMC article. Review. - SGLT-2 inhibitors: new horizons for rheumatologists.
Chakrabarti K, McCune WJ. Chakrabarti K, et al. Curr Opin Rheumatol. 2024 Sep 1;36(5):351-359. doi: 10.1097/BOR.0000000000001030. Epub 2024 Jul 24. Curr Opin Rheumatol. 2024. PMID: 39007236 Free PMC article. Review. - Is GFR decline induced by SGLT2 inhibitor of clinical importance?
Günes-Altan M, Bosch A, Striepe K, Bramlage P, Schiffer M, Schmieder RE, Kannenkeril D. Günes-Altan M, et al. Cardiovasc Diabetol. 2024 May 29;23(1):184. doi: 10.1186/s12933-024-02223-0. Cardiovasc Diabetol. 2024. PMID: 38811998 Free PMC article. Clinical Trial. - Sodium-glucose co-transporter protein 2 (SGLT2) inhibitors for people with chronic kidney disease and diabetes.
Natale P, Tunnicliffe DJ, Toyama T, Palmer SC, Saglimbene VM, Ruospo M, Gargano L, Stallone G, Gesualdo L, Strippoli GF. Natale P, et al. Cochrane Database Syst Rev. 2024 May 21;5(5):CD015588. doi: 10.1002/14651858.CD015588.pub2. Cochrane Database Syst Rev. 2024. PMID: 38770818 Review.
References
- American Diabetes Association : Standards of medical care in diabetes–2015. Diabetes Care 38[Suppl]: S1–S93, 2015
- Mudaliar S, Polidori D, Zambrowicz B, Henry RR: Sodium-glucose cotransporter inhibitors: effects on renal and intestinal glucose transport: from bench to bedside. Diabetes Care 38: 2344–2353, 2015 - PubMed
- Cefalu WT, Leiter LA, Yoon KH, Arias P, Niskanen L, Xie J, Balis DA, Canovatchel W, Meininger G: Efficacy and safety of canagliflozin versus glimepiride in patients with type 2 diabetes inadequately controlled with metformin (CANTATA-SU): 52 week results from a randomised, double-blind, phase 3 non-inferiority trial. Lancet 382: 941–950, 2013 - PubMed
- Brewster UC, Setaro JF, Perazella MA: The renin-angiotensin-aldosterone system: cardiorenal effects and implications for renal and cardiovascular disease states. Am J Med Sci 326: 15–24, 2003 - PubMed
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Research Materials
Miscellaneous