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The Management of Patients with Heart Failure and Diabetes
Published in Andreas P. Kalogeropoulos, Hal A. Skopicki, Javed Butler, Heart Failure, 2023
Canagliflozin was examined in the CANVAS trial and was shown to reduce HF hospitalizations and combined cardiovascular events (cardiovascular mortality, non-fatal myocardial infarction, and non-fatal CVA), as well as to slow the progression of kidney disease. Canagliflozin was, however, associated with an increased incidence of lower limb amputations.30
Decentralized Clinical Trials: A New Paradigm for New Medical Product Development and Digital Therapeutics
Published in Oleksandr Sverdlov, Joris van Dam, Digital Therapeutics, 2023
Isaac R. Rodriguez-Chavez, Greg Licholai
A use case of DCT approaches applied to therapies includes tolterodine which was initially assessed for safety and efficacy to treat overactive bladder in a full DCT (phase 4) (Orri et al., 2014). Another use case is the CHIEF-HT full DCT (phase 2) that tested the efficacy of 12 weeks of canagliflozin for the treatment of heart failure, regardless of ejection fraction or diabetes status, on the reduction of heart failure symptoms (Spertus et al., 2021). Aspirin has been tested in a full DCT to prevent atherosclerotic cardiovascular disease (Jones et al., 2021). DCT approaches have also been deployed in dermatological conditions since skin diseases frequently are not life-threatening and do not often involve complex assessments; they are visual, and it is relatively easy to evaluate skin diseases virtually by making correct diagnoses based on photographs and patient symptomatology (Ali et al., 2020). A topical probiotic spray to treat mild to moderate acne was tested in a hybrid DCT (phase 2b) (Singer et al., 2018). The efficacy and safety of rituximab versus mycophenolate mofetil to treat Pemphigus Vulgaris (a rare autoimmune disease that causes blisters on the skin and mucous membranes throughout the body) have been evaluated in a hybrid DCT (phase 3) (Werth et al., 2021). The impact of missed bolus insulin doses in diabetes has been reported in a hybrid DCT (phase 4).66 Topical patidegib has been evaluated for basal cell carcinomas (Gorlin syndrome).67
Endocrine Disorders, Contraception, and Hormone Therapy during Pregnancy
Published in “Bert” Bertis Britt Little, Drugs and Pregnancy, 2022
No data are available regarding excretion of canagliflozin into breast milk, but in rats the transfer of the drug into milk seems equivalent to maternal serum concentrations. It is an FDA category C drug under the old classification system.
Novel therapeutic agents for the treatment of diabetic kidney disease
Published in Expert Opinion on Investigational Drugs, 2020
Rachel E. Hartman, P.S.S. Rao, Mariann D. Churchwell, Susan J. Lewis
Currently, the most promising available agents for DKD are the SGLT2 inhibitors with their novel mechanism of blocking glucose reuptake in the proximal tubule via SGLT2 that has led to therapies with measurable outcomes in delaying ESKD in patients with DKD. A limitation with SGLT2 inhibitors was that they were not FDA approved for patients with an eGFR < 45 mL/min/1.73 m2 (Table 3), although clinical trials with SGLT2 inhibitors have enrolled patients with an eGFR as low as 20 mL/min/1.73 m2. The CREDENCE trial did not include patients with an eGFR < 30 mL/min/1.73 m2, but hyperkalemia and acute kidney injury were lower in the canagliflozin group. These findings have prompted an examination of dosing recommendations for canagliflozin. DAPA-CKD and EMPA-Kidney trials may expand our understanding of SGLT2 inhibitors in patients with severe CKD as both studies have enrolled patients with eGFR < 30 mL/min/1.73 m2 and UACR ≥ 200 mg/g [39,40,168,169].
An update of SGLT1 and SGLT2 inhibitors in early phase diabetes-type 2 clinical trials
Published in Expert Opinion on Investigational Drugs, 2019
Ernest Adeghate, Sahar Mohsin, Faisal Adi, Fares Ahmed, Ali Yahya, Huba Kalász, Kornelia Tekes, Ernest A. Adeghate
Canagliflozin, developed by Johnson & Johnson, USA, was approved in 2013 by the FDA (USA) for the treatment of T2DM. The CANVAS (Canagliflozin Cardiovascular Assessment Study), a large study spearheaded in Australia involving more than 10,000 patients who were given canagliflozin randomly versus placebo, showed a significantly lower risk of cardiovascular illness coupled with a marked reduction in the rate of hospitalization for heart and kidney failure [35,36]. This study lasted over 4 years, indicating that some of the long-term effects of canagliflozin were also in display. In a similar trend, CREDENCE, a recent randomized controlled study examining the effect of canagliflozin on cardiovascular and renal outcome in patients with T2DM, showed that this SGLT2 inhibitor improves cardiovascular (e.g. rate of heart failure hospitalization, non-fatal myocardial infarction, etc.) and renal outcomes (e.g. kidney failure) [37]. In a recently published double blind, randomized CREDENCE Trial, canagliflozin was reported to reduce the risk of cardiovascular and renal failure in T2DM subjects with renal disease [37,38]. Canagliflozin can be prescribed for oral administration (100–300 mg tablets). Figure 1, Table 1.
Cardiovascular risk in chronic kidney disease: what is new in the pathogenesis and treatment?
Published in Postgraduate Medicine, 2018
Angelika Bazyluk, Jolanta Malyszko, Edyta Zbroch
The EMPA-REG – OUTCOME trial enrolled only patients with established CVD [46], which states a limitation for the study and raises for discussion advisability of conclusions regarding general population. It did not provide data about empagliflozin efficacy in primary prevention of CVD. The CANVAS trial (CANagliflozin cardioVascular Assessment Study), concerning another representative of the SGLT-2 inhibitors drug class canagliflozin, enrolled participants with prior CV events or at least 50 years of age and risk factors for CVD [50]. The results of the study showed comparable effectiveness in lowering the risk for death from CV causes and hospitalization for heart failure. The effects on renal outcomes suggested possible benefit; however, they were not significant on the basis of prespecified statistical methods. The ongoing CREDENCE trial (Evaluation of the Effects of Canagliflozin on Renal and Cardiovascular Outcomes in Participants With Diabetic Nephropathy) will supply reliable data about the influence of canagliflozin on renal function [51]. It is worthy mentioned about specific adverse effects of canagliflozin treatment. The CANVAS trial confirmed previously described risk for fracture events [52] and demonstrated increased incidence of lower limb amputation [50]. Given the fact, the use of canagliflozin in patients with peripheral artery disease should be carefully considered. The data mentioned above suggest advisability of combined therapy with SGLT-2 inhibitors and ACEI/ARB among patients with CKD and DM with high CV risk.