Clinical potential of canagliflozin in cardiovascular risk reduction in patients with type 2 diabetes

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Term Occurence Count Dictionary
metformin 3 endocrinologydiseasesdrugs
sitagliptin 12 endocrinologydiseasesdrugs
type 2 diabetes mellitus 3 endocrinologydiseases
dapagliflozin 7 endocrinologydiseasesdrugs
diabetes mellitus 5 endocrinologydiseases
diabetic foot 1 endocrinologydiseases
hyperglycemia 1 endocrinologydiseases
hypoglycemia 1 endocrinologydiseases

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Select Drug Character Offset Drug Term Instance
dapagliflozin 4439 selective for SGLT2. Canagliflozin has a selectivity ratio of approximately 160–410 for SGLT2 over SGLT1, dapagliflozin a ratio of 1,200 and empagliflozin 2,600.[11] Due to canagliflozin’s lesser SGLT2 to SGLT1 selectivity,
dapagliflozin 17248 included in this study who were taking an SGLT2 inhibitor, 53% were taking canagliflozin, 42% were taking dapagliflozin , and 5% were taking empagliflozin.[15]An additional study comparing canagliflozin to other AHAs was
dapagliflozin 24684 and nonfatal stroke was still demonstrated. The recently completed DECLARE-TIMI 58 trial evaluating dapagliflozin compared with placebo in patients with T2DM and high CVD risk found dapagliflozin to be non-inferior
dapagliflozin 24766 trial evaluating dapagliflozin compared with placebo in patients with T2DM and high CVD risk found dapagliflozin to be non-inferior for major cardiovascular AEs and demonstrated a statistically significant reduction
dapagliflozin 25247 of SGLT2 inhibitors specifically in kidney disease, including CREDENCE (canagliflozin) and DAPA-CKD ( dapagliflozin ). It should be noted that while these cardiovascular and renal endpoint trials are informative, they
dapagliflozin 26464 higher incidence of any amputation among patients with DM (0.32%) compared to empagliflozin (0.09%) and dapagliflozin (0%).[43] There are a few possible mechanisms whereby amputation risk could have been increased in the
dapagliflozin 35244 components of CV eventsCVD-REAL[15]Retrospective cohortSGLT2 inhibitor (canagliflozin, empagliflozin, or dapagliflozin ) or other oral or injectable glucose lowering agentn=262,339 (including 132,572 canagliflozin)Mean age
metformin 5713 American Diabetes Association recommends the addition of canagliflozin to lifestyle management and metformin among those with T2DM and atherosclerotic CVD to reduce major adverse cardiovascular events (MACE).[1]
metformin 9527 experienced similar BP lowering effects.[20] When canagliflozin was evaluated as add-on therapy to metformin and a sulfonylurea, canagliflozin provided significant reductions in SBP and DBP compared to placebo.[20]
metformin 36218 high-density lipoprotein cholesterol; HF, heart failure; HTN, hypertension; MC, multi-center; MET, metformin ; MI, myocardial infarction; NT-proBNP, N-terminal pro-brain natriuretic peptide; NYHA, New York Heart
sitagliptin 6505 patients with T2DM studied the effects of canagliflozin in comparison to placebo or other AHAs, such as sitagliptin , glimepiride, DPP4 inhibitors (DPP4-Is), GLP-1 receptor-agonists, and insulin. Key study endpoints included
sitagliptin 9693 reductions in SBP and DBP compared to placebo.[20] Several clinical trials compared canagliflozin to sitagliptin 100 mg, a DPP-4 inhibitor, to assess efficacy and safety. Canagliflozin 100 mg and 300 mg were associated
sitagliptin 9866 Canagliflozin 100 mg and 300 mg were associated with significant reductions in SBP and DBP compared to sitagliptin 100 mg across all three published trials.[21]–[23] Additionally, minimal changes in pulse rate were
sitagliptin 10037 Additionally, minimal changes in pulse rate were observed between both doses of canagliflozin compared to sitagliptin .Body weight reductionsObesity and sedentary lifestyle contribute to the progression of T2DM and increase
sitagliptin 10982 with significant weight loss seen in the canagliflozin treatment groups.[17] In the trials that used sitagliptin 100 mg as an active control, canagliflozin was associated with significant body weight reductions compared
sitagliptin 11104 an active control, canagliflozin was associated with significant body weight reductions compared to sitagliptin (P<0.001).[21]–[23] One 52-week trial reported weight loss from canagliflozin to have occurred more
sitagliptin 11431 study, canagliflozin resulted in significant weight loss in all studied regimens compared to placebo and sitagliptin 100 mg (P<0.001).[24]Changes in renal functionRenal function decline is a frequent complication of T2DM
sitagliptin 20696 intravascular volume reduction was low and similar in canagliflozin and placebo.[7],[14],[17],[19],[20] In the sitagliptin -controlled studies, incidence of postural dizziness and hypotension were low across all groups. In the
sitagliptin 20962 higher incidence of intra-vascular volume reduction AEs compared to canagliflozin 300 mg and placebo/ sitagliptin .[21]–[23] The events of postural dizziness and hypotension that did occur with canagliflozin were
sitagliptin 21453 AEs compared to placebo.[7],[14],[17],[19],[20] In the Phase 3 studies that compared canagliflozin to sitagliptin , canagliflozin resulted in a higher incidence of osmotic diuresis AEs.[21]–[23] The majority of reported
sitagliptin 22143 Several trials reported that canagliflozin caused an increase in hemoglobin and hematocrit, whereas sitagliptin and placebo caused a decrease in both values.[7],[18]–[23]Discussion/clinical considerationsThe class
sitagliptin 36461 placebo-controlled trial; QoL, quality of life; R, randomized; SBP, systolic blood pressure; SITA, sitagliptin ; T2DM, type 2 diabetes mellitus; TG, triglyceride.Table 2Reported cardiovascular clinical endpoint dataStudyCanagliflozin
Select Disease Character Offset Disease Term Instance
diabetes mellitus 481 12/2018AbstractCardiovascular disease is the leading cause of morbidity and mortality among patients with diabetes mellitus , as well as the leading diabetes-associated health care cost. The prevalence and associated impact of
diabetes mellitus 1100 identified and included within the review. Overall these studies demonstrate that among patients with type 2 diabetes mellitus , canagliflozin results in decreased systolic and diastolic blood pressure, lower body weight, and also
diabetes mellitus 2098 reduction.IntroductionCardiovascular disease (CVD) is the leading cause of morbidity and mortality among individuals with diabetes mellitus (DM) and comprises the largest component of direct and indirect health care costs associated with DM.[1],[2]
diabetes mellitus 3036 (AHAs), the SGLT2 inhibitors, has been developed. These agents are approved for the treatment of type 2 diabetes mellitus (T2DM), and have shown an estimated reduction in HbA1c by 0.5% to 1%.[4] Based on the mechanism of action,
diabetes mellitus 36487 QoL, quality of life; R, randomized; SBP, systolic blood pressure; SITA, sitagliptin; T2DM, type 2 diabetes mellitus ; TG, triglyceride.Table 2Reported cardiovascular clinical endpoint dataStudyCanagliflozin doseNumber
diabetic foot 26734 unknown. The overall amputation rate in patients with T2DM has declined over the last few decades, but diabetic foot disease (DFD) remains prevalent, increasing risk of lower-extremity amputation in itself.[43],[44] In
hyperglycemia 17905 evaluate the underlying effect of these agents on vascular function and cardiac function. It is known that hyperglycemia -related arterial stiffness can contribute to new-onset or worsening hypertension.[30] Empagliflozin
hypoglycemia 20092 to placebo. Such pre-specified AEs included: urinary tract infections, genital mycotic infections, hypoglycemia , and events related to osmotic diuresis.Safety evaluations related to cardiovascular endpoints included
type 2 diabetes mellitus 1093 identified and included within the review. Overall these studies demonstrate that among patients with type 2 diabetes mellitus , canagliflozin results in decreased systolic and diastolic blood pressure, lower body weight, and also
type 2 diabetes mellitus 3029 agents (AHAs), the SGLT2 inhibitors, has been developed. These agents are approved for the treatment of type 2 diabetes mellitus (T2DM), and have shown an estimated reduction in HbA1c by 0.5% to 1%.[4] Based on the mechanism of action,
type 2 diabetes mellitus 36480 trial; QoL, quality of life; R, randomized; SBP, systolic blood pressure; SITA, sitagliptin; T2DM, type 2 diabetes mellitus ; TG, triglyceride.Table 2Reported cardiovascular clinical endpoint dataStudyCanagliflozin doseNumber

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