Effects of canagliflozin are mostly observed at first follow-up, within 6 months of commencement: results for the ABCD canagliflozin audit
DOI:
https://doi.org/10.15277/bjd.2020.258Keywords:
canagliflozin, real-world, observational, HbA1c, follow-upAbstract
Introduction: Canagliflozin was initially approved for use in the UK in March 2013. Randomised control trial evidence has demonstrated multiple beneficial effects. Many of these are present at initial follow-up and within 26 weeks of randomised control trial data. Our aim was to assess whether the beneficial effects of canagliflozin on multiple clinical and biochemical parameters occurred prior to first follow-up and, if so, whether these continued to improve or simply persisted at second follow-up.
Methods: Data were extracted from the ABCD nationwide canagliflozin audit to include a minimum dataset of a baseline value and one (or two) follow-ups for each value.
Results: A total of 1,214 patient datasets were identified and used in the analysis: mean±SD age 60.1±10.6 years; median duration of diabetes 8 (IQR 2.4–12.6 years); baseline HbA1c 75.1±17.4 mmol/mol (9.0±1.59%) and weight 97.8±22.0 kg. 68.3% of the patients were Caucasian where this was known (n=183). At first follow-up (median 0.7 years) from baseline: change in HbA1c −9.3 mmol/mol (95% CI −8.2 to −10.4; p<0.0001), weight −2.3 kg (95% CI −1.9 to −2.5; p<0.0001); BMI −0.7 kg/m2 (95% CI −0.6 to −0.8; p<0.0001); alanine aminotransferase −2 U/L (95% CI −1.3 to −2.7; p<0.0001); eGFR −0.9 mL/min/1.73 m2 (95% CI −0.4 to −1.4; p<0.001); systolic blood pressure (BP) −2.6 mmHg (95% CI −1.6 to −3.5; p<0.0001) and diastolic BP −0.9 mmHg (95% CI −0.2 to −1.6; p<0.001). Significant differences persisted comparing second follow-up (median 1.2 years) to baseline, but no further significant changes were noted between first follow-up and second follow-up other than in weight and BMI with further change in weight −0.65 kg (95% CI −0.2 to −1.1; p=0.047).
Conclusion: The improvements following canagliflozin in this real-world cohort seem to occur within the first 0.7 years of treatment, which is similar to randomised controlled trial data. These improvements seem to be maintained over the next 6 months, with significant further weight loss occurring between 0.7 years and 1.2 years, although the mechanism of this is unclear and might be due to confounders. More evidence on this point is needed.
References
Johnson & Johnson. U.S. FDA approves INVOKANA™ (Canagliflozin) for the treatment of adults with type 2 diabetes. 2013. Available from: https://www.jnj.com/media-center/press-releases/us-fda-approves-invokana-canagliflozin-for-the-treatment-of-adults-with-type-2-diabetes (accessed 13 Jan 2020).
Cefalu WT, Leiter LA, Yoon K-H, et al. 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 2013;382(9896):941–50. https://doi.org/10.1016/S0140-6736(13)60683-2
Forst T, Guthrie R, Goldenberg R, et al. Efficacy and safety of canagliflozin over 52 weeks in patients with type 2 diabetes on background metformin and pioglitazone. Diabetes Obes Metab 2014;16(5):467–77. https://doi.org/10.1111/dom.12273
Lavalle-Gonzalez FJ, Januszewicz A, Davidson J, et al. Efficacy and safety of canagliflozin compared with placebo and sitagliptin in patients with type 2 diabetes on background metformin monotherapy: a randomised trial. Diabetologia 2013;56(12):2582–92. https://doi.org/10.1007/s00125-013-3039-1
Rodbard HW, Peters AL, Slee A, et al. The effect of canagliflozin, a sodium glucose cotransporter 2 inhibitor, on glycemic end points assessed by continuous glucose monitoring and patient-reported outcomes among people with type 1 diabetes. Diabetes Care 2017;40(2):171–80. https://doi.org/10.2337/dc16-1353
Stenlof K, Cefalu WT, Kim K-A, et al. Long-term efficacy and safety of canagliflozin monotherapy in patients with type 2 diabetes inadequately controlled with diet and exercise: findings from the 52-week CANTATA-M study. Curr Med Res Opin 2014;30(2):163–75. https://doi.org/10.1185/03007995.2013.850066
Wilding JP, Charpentier G, Hollander P, et al. Efficacy and safety of canagliflozin in patients with type 2 diabetes mellitus inadequately controlled with metformin and sulphonylurea: a randomised trial. Int J Clin Pract 2013;67(12):1267–82. https://doi.org/10.1111/ijcp.12322
Xiong W, Xiao MY, Zhang M, Chang F. Efficacy and safety of canagliflozin in patients with type 2 diabetes: a meta-analysis of randomized controlled trials. Medicine (Baltimore) 2016;95(48):e5473. https://doi.org/10.1097/MD.0000000000005473
Perkovic V, Jardine MJ, Neal B, et al. Canagliflozin and renal outcomes in type 2 diabetes and nephropathy. N Engl J Med 2019;380(24):2295–306. https://doi.org/10.1056/NEJMoa1811744
Perkovic V, de Zeeuw D, Mahaffey KW, et al. Canagliflozin and renal outcomes in type 2 diabetes: results from the CANVAS program randomised clinical trials. Lancet Diabetes Endocrinol 2018;6(9):691–704. https://doi.org/10.1016/S2213-8587(18)30141-4
Cusi K, Bril F, Barb D, et al. Effect of canagliflozin treatment on hepatic triglyceride content and glucose metabolism in patients with type 2 diabetes. Diabetes Obes Metab 2019;21(4):812–21. https://doi.org/10.1111/dom.13584
Gautam A, Agrawal PK, Doneria J, Nigam A. Effects of canagliflozin on abnormal liver function tests in patients of type 2 diabetes with non-alcoholic fatty liver disease. J Assoc Physicians India 2018;66(8):62–6.
Bajaj HS, Brown RE, Bhullar L, Sohi N, Kalra S, Aronson R. SGLT2 inhibitors and incretin agents: associations with alanine aminotransferase activity in type 2 diabetes. Diabetes Metab 2018;44(6):493–9. https://doi.org/10.1016/j.diabet.2018.08.001
Itani T, Ishihara T. Efficacy of canagliflozin against nonalcoholic fatty liver disease: a prospective cohort study. Obes Sci Pract 2018;4(5):477–82. https://doi.org/10.1002/osp4.294
Leiter LA, Forst T, Polidori D, Balis DA, Xie J, Sha S. Effect of canagliflozin on liver function tests in patients with type 2 diabetes. Diabetes Metab 2016;42(1):25–32. https://doi.org/10.1016/j.diabet.2015.10.003
Published
Issue
Section
License
Publish & Transfer of Copyright Agreement
For the mutual benefit and protection of the Author and the Journal Owner/Publisher it is necessary that the Author provides formal written Consent to Publish and Transfer of Copyright before publication of the Work.