Can canagliflozin improve renal outcome and associated nephropathy in patients with

DM2 and CKD?

Background

Diabetes mellitus type 2 (DM2) disease is a leading killer disease in the world. This disease has been associated with a number of health conditions, including kidney failure. Chronic kidney disease (CKD) is a common condition associated with diabetes mellitus type 2 can also contribute to an increased risk of mortality as a result of cardiovascular conditions.

The prevalence of diabetes type has been on the rise in recent times, with the disease being the major cause of kidney failure It us predicted that by the year 2035, a tune of up to 6 million people will be diagnosed with kidney failure as a result of diabetes mellitus type 21. Canagliflozin, which is an oral SGLT2 inhibitor, has been tested in a number of studies as to whether it can contribute positively to the health status of patients with DM2 and CKD. Trials of canagliflozin have been done, and it is supposed that canagliflozin can improve renal outcomes amongst patients with CKD and DM22.

Literature Search Strategy:

In a study carried out by (Perkovic et al 2019)3, selected patients with DM 2 and CKD were sampled to be administered with canagliflozin. A randomized research method was used, whereby each patient was to be given canagliflozin of 100 mg daily. Before the actual study was conducted, every patient was treated with a system blockade.

Additionally, as another requirement in preparing the patients, each one of them was to receive a stable dosage of an inhibitor that converts angiotensin, also called angiotensin-receptor blockade. The blockade was to be received at least four weeks before the process of randomization would start. Patients who were suspected to have kidney failure that was not related to diabetes type 2 disease, or who had initially been treated for kidney disease using immunosuppression, or had those that undergone kidney transplant procedures were not included in the study.  

Results/Literature Analysis:

The outcomes of this study was expected to be as follows: severe kidney damage that would include a 30 days dialysis process, kidney transplant, augmenting the level of serum creatinine, death from cardiovascular disease or renal problems. Apart from these, all other outcomes were considered exploratory4

To ensure safety during the process of the study, health and safety independent committees were formed to oversee the whole process. Evaluations for safety included carrying out an assessment of volatile situations and carrying out laboratory tests. Renal and cardiovascular safety considerations were overseen by another independent safety and health committee whose members were oblivious of the assignments of each group5.

A promising study was carried out to establish the effect of canagliflozin on the renal outcome in patients with DM2 and CKD.  However, due to safety concerns, the study was halted early, according as the committee in charge of health and safety planned it. Only patients with diabetes mellitus type 2 disease and with hemoglobin presence of 7 % to 12 % (severe kidney failure conditions) were considered.

The participants who were enjoined in this study included both males and females of a median age of 30. A total of 4401 patients took part in the study. There were two trial groups; the canagliflozin group and the placebo group.

The approximated risk for the primary expectations was 30 % in the placebo group. Event rates for the canagliflozin group were 43.2, while those of the placebo group were 61.2. In the placebo group, the death risk from renal causes was observed to be 34% lower than it was observed with the group. The approximated death risk from acute kidney failure was observed to be lower by 32%. At the same time, the canagliflozin group exhibited a lower prevalence of cardiovascular problems, and consequently, lower hospitalizations. For amputations of fractures, both groups were observed to be similar, with very small difference margins6

Recommendations/Summary:

Amongst the patients with DM 2 and CKD, the canagliflozin group was observed to exhibit a lower risk of cardiovascular problems (43.2 per 1000 patient – years) while with the placebo group the risk was (61.2 per 1000 patient-years). The risk of getting the cardiovascular disease and kidney problems was observed to be a little higher with the placebo group.

For the secondary outcomes, patients in the canagliflozin class exhibited a reduced risk as deaths resulting from cardiovascular problems, stroke death, or hospitalization. The general risk for acute kidney problems and doubling of serum creatinine or death as a result of kidney failure was observed to have reduced by 34 % in the canagliflozin group compared with the placebo group. With the risk of cardiovascular problems, there was but an insignificant difference between the two groups. The risk of death from any cause was 0.83. 

Due to the lower risk associated with taking of canagliflozin, it is strongly recommended for patients with cardiovascular problems as a result of diabetes mellitus type 2 and acute kidney failure. According to the evidence that has been presented above, I would recommend to Dr. Wilson that he addscanagliflozin to his regimen as evidence has shown that it will do his patients only good. Indeed, canagliflozin can improve renal outcomes that are associated with nephropathy in patients having DM2 and CKD.

Closing:

I would like to take this chance to appreciate everybody who positively contributed to the success of this study. More especially, I thank all the patients, safety committee members, trial teams and statistical officers for being caring enough to expend their precious time in this study.

References

  1. Jardine, M. J., Mahaffey, K. W., Neal, B., Agarwal, R., Bakris, G. L., Brenner, B. M., & Edwards, R. (2017). The Canagliflozin and Renal Endpoints in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) study rationale, design, and baseline characteristics. American journal of nephrology, 46(6), 462-472.
  • Penno, G., Garofolo, M., & Del Prato, S. (2016). Dipeptidyl peptidase-4 inhibition in chronic kidney disease and potential for protection against diabetes-related renal injury. Nutrition, Metabolism and Cardiovascular Diseases, 26(5), 361-373.
  • V. Perkovic, M.J. Jardine, B. Neal, S. Bompoint, H.J.L. Heerspink, D.M. Charytan, R. Edwards, R. Agarwal, G. Bakris, S. Bull, C.P. Cannon, G. Capuano, P.-L. Chu, D. de Zeeuw, T. Greene, A. Levin, C. Pollock, D.C. Wheeler, Y. Yavin, H. Zhang, B. Zinman, G. Meininger, B.M. Brenner, and K.W. Mahaffey, (2019)Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy. vol. 380
  • Perkovic, V., de Zeeuw, D., Mahaffey, K. W., Fulcher, G., Erondu, N., Shaw, W., …& Neal, B. (2018). Canagliflozin and renal outcomes in type 2 diabetes: results from the CANVAS Program randomised clinical trials. The Lancet Diabetes & Endocrinology, 6(9), 691-704.
  • Perkovic, V., Jardine, M., Vijapurkar, U., &Meininger, G. (2015). Renal effects of canagliflozin in type 2 diabetes mellitus. Current medical research and opinion, 31(12), 2219-2231.
  • Weir, M. R. (2016). The kidney and type 2 diabetes mellitus: therapeutic implications of SGLT2 inhibitors. Postgraduate medicine, 128(3), 290-298
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