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  1. Oshima M, Jardine MJ, Agarwal R, Bakris G, Cannon CP, Charytan DM, et al.
    Kidney Int, 2021 04;99(4):999-1009.
    PMID: 33316282 DOI: 10.1016/j.kint.2020.10.042
    Canagliflozin slows the progression of chronic kidney disease in patients with type 2 diabetes and induces a reversible acute drop in estimated glomerular filtration rate (eGFR), believed to be a hemodynamic effect. Predictors of the initial drop and its association with long-term eGFR trajectories and safety outcomes are unknown. To assess this, we performed a post-hoc analysis of 4289 participants in the CREDENCE trial with type 2 diabetes and chronic kidney disease equally split into treatment and placebo groups who had eGFR measured at both baseline and week three. The eGFR was categorized at week three as greater than a 10% decline; between 0 and 10% decline; and no decline. Long-term eGFR trajectories and safety outcomes were estimated in each category of acute eGFR change by linear mixed effects models and Cox regression after adjustment for baseline characteristics and medications use. Significantly more participants in the canagliflozin (45%) compared to the placebo (21%) group experienced an acute drop in eGFR over 10%. An over 30% drop occurred infrequently (4% of participants with canagliflozin and 2% with placebo). The odds ratio for a drop in eGFR over 10% with canagliflozin compared to placebo was significant at 3.03 (95% confidence interval 2.65, 3.47). Following the initial drop in eGFR, multivariable adjusted long-term eGFR trajectories, as well as overall and kidney safety profiles, in those treated with canagliflozin were similar across eGFR decline categories. Thus, although acute drops in eGFR over 10% occurred in nearly half of all participants following initiation of canagliflozin, the clinical benefit of canagliflozin was observed regardless. Additionally, safety outcomes were similar among subgroups of acute eGFR drop.
    Matched MeSH terms: Canagliflozin/adverse effects
  2. Thanapairoje K, Junsiritrakhoon S, Wichaiyo S, Osman MA, Supharattanasitthi W
    J Basic Clin Physiol Pharmacol, 2023 May 01;34(3):277-289.
    PMID: 36631934 DOI: 10.1515/jbcpp-2022-0242
    Ageing is the process generated by senescent cells, free radicals, inflammation and other relevant factors. Ageing contributes to age-related diseases that affect the quality of life. People are interested in anti-ageing intervention and many scientists attempt to search for anti-ageing medicines. This review focused on describing in vivo anti-ageing activity of US-FDA-approved drugs and found that alogliptin, canagliflozin and metformin might produce anti-ageing activity via AMPK activation. Rapamycin and canagliflozin are capable to inhibit mTOR to promote lifespan. Atracurium, carnitine and statins act as DAF-16 activators, which potentially contribute to anti-ageing activity. Hydralazine, lisinopril, rosiglitazone and zidovudine may help stabilize genomic integrity to prolong life expectancy. Other indirect mechanisms, including insulin-lowering effect by acarbose and calcium channel blocking activity by verapamil may also promote longevity. Interestingly, some drugs (i.e., canagliflozin, metformin, rapamycin and acarbose) are likely to demonstrate a lifespan-promoting effect predominantly in male animals. These pre-clinical data might provide mechanistic and phenotypic perspectives to better understand the targets of anti-ageing interventions.
    Matched MeSH terms: Canagliflozin
  3. Lim LL, Tan AT, Moses K, Rajadhyaksha V, Chan SP
    J Diabetes Complications, 2017 Feb;31(2):494-503.
    PMID: 27866701 DOI: 10.1016/j.jdiacomp.2016.10.008
    The burden of type 2 diabetes (T2DM) in East Asia is alarming. Rapid modernization and urbanization have led to major lifestyle changes and a tremendous increase in the prevalence of obesity, metabolic syndrome, and diabetes mellitus. The development of T2DM at a younger age, with lower body mass index, higher visceral adiposity, and more significant pancreatic beta-cell dysfunction compared to Caucasians are factors responsible for the increased prevalence of T2DM in East Asians. Sodium-glucose Cotransporter-2 (SGLT2) inhibitors (canagliflozin, dapaglifozin, empagliflozin, etc.) reduce renal glucose reabsorption, leading to favorable effects on glycemic, blood pressure, and weight control. The insulin-independent mechanism enables their use as monotherapy or combination therapy with insulin and other oral antidiabetic agents. The role of SGLT2 inhibitors in the management of T2DM among East Asians is an interesting area of research, given that East Asians have been proven to be uniquely different from Caucasians. This review provides comprehensive coverage of the available literature not only on the efficacy and safety, but also on the recent cardiovascular and renal outcomes of SGLT2 inhibitors, focusing among East Asians.
    Matched MeSH terms: Canagliflozin/adverse effects; Canagliflozin/therapeutic use
  4. Wada T, Mori-Anai K, Kawaguchi Y, Katsumata H, Tsuda H, Iida M, et al.
    J Diabetes Investig, 2022 Jan;13(1):54-64.
    PMID: 34212533 DOI: 10.1111/jdi.13624
    AIMS/INTRODUCTION: The sodium-glucose cotransporter 2 inhibitor, canagliflozin, reduced kidney failure and cardiovascular events in the Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) trial. We carried out a post-hoc analysis to evaluate the efficacy and safety of canagliflozin in a subgroup of participants in East and South-East Asian (EA) countries who are at high risk of renal complications.

    MATERIALS AND METHODS: Participants with an estimated glomerular filtration rate of 30 to <90 mL/min/1.73 m2 and urinary albumin-to-creatinine ratio of >300-5,000 mg/g were randomized to 100 mg of canagliflozin or a placebo. The effects of canagliflozin treatment on pre-specified efficacy and safety outcomes were examined using Cox proportional hazards regression between participants from EA countries (China, Japan, Malaysia, the Philippines, South Korea and Taiwan) and the remaining participants.

    RESULTS: Of 4,401 participants, 604 (13.7%) were from EA countries; 301 and 303 were assigned to the canagliflozin and placebo groups, respectively. Canagliflozin lowered the risk of primary outcome (composite of end-stage kidney disease, doubling of serum creatinine level, or renal or cardiovascular death) in EA participants (hazard ratio 0.54, 95% confidence interval 0.35-0.84). The effects of canagliflozin on renal and cardiovascular outcomes in EA participants were generally similar to those of the remaining participants. Safety outcomes were similar between the EA and non-EA participants.

    CONCLUSIONS: In the CREDENCE trial, the risk of renal and cardiovascular events was safely reduced in participants from EA countries at high risk of renal events.

    Matched MeSH terms: Canagliflozin/therapeutic use*
  5. Ji L, Han P, Liu Y, Yang G, Dieu Van NK, Vijapurkar U, et al.
    Diabetes Obes Metab, 2015 Jan;17(1):23-31.
    PMID: 25175734 DOI: 10.1111/dom.12385
    To evaluate the efficacy and safety of canagliflozin, a sodium glucose co-transporter 2 inhibitor, in Asian patients with type 2 diabetes mellitus (T2DM) inadequately controlled by metformin or metformin in combination with sulphonylurea.
    Matched MeSH terms: Canagliflozin
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