An evidence-based practice-oriented review focusing on canagliflozin in the management of type 2 diabetes.

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Term Occurence Count Dictionary
diabetes mellitus 4 endocrinologydiseases
pioglitazone 1 endocrinologydiseasesdrugs
type 1 diabetes mellitus 1 endocrinologydiseases
Fanconi syndrome 1 endocrinologydiseases
dapagliflozin 13 endocrinologydiseasesdrugs
renal glycosuria 1 endocrinologydiseases
sitagliptin 5 endocrinologydiseasesdrugs
hypoglycemia 8 endocrinologydiseases
obesity 1 endocrinologydiseases
type 2 diabetes mellitus 2 endocrinologydiseases
diabetic ketoacidosis 1 endocrinologydiseases
hyperglycemia 6 endocrinologydiseases
hyperphosphatemia 1 endocrinologydiseases
metformin 8 endocrinologydiseasesdrugs

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Review

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Select Drug Character Offset Drug Term Instance
dapagliflozin 8505 was the first FDA-approved agent in class in the US market in 2013. Others have followed, including dapagliflozin (FDA approved in January 2014) and empagliflozin (FDA approved in July 2014), with others in development.Studies
dapagliflozin 19561 is in line with what is observed in FRG.To investigate the diuretic properties of SGLT2 inhibitors, dapagliflozin was compared with placebo and hydrochlorothiazide in a randomized, double-blind trial.[36] It revealed
dapagliflozin 19708 hydrochlorothiazide in a randomized, double-blind trial.[36] It revealed that the 24-h BP decrease for dapagliflozin was intermediate between the other two arms of the study with a decrease of −0.9 mmHg (95% confidence
dapagliflozin 19946 −4.2, +2.4), −3.3 mmHg (95% CI: −6.8, +0.2), and −6.6 mmHg (95% CI: −9.9, −3.2) for placebo, dapagliflozin , and hydrochlorothiazide, respectively. Curiously, office BP recordings were the lowest for dapagliflozin.
dapagliflozin 20052 dapagliflozin, and hydrochlorothiazide, respectively. Curiously, office BP recordings were the lowest for dapagliflozin . The authors believed this to be secondary to BP recordings being taken during the daytime hours. Subgroup
dapagliflozin 20444 erythrocytes and 125I-labeled human serum albumin. Changes from baseline in plasma volume for placebo, dapagliflozin , and hydrochlorothiazide groups were +5.2% (−2.5 to +8.7), −7.3% (−12.4 to −4.8), and +2.8%
dapagliflozin 20808 However, the study also revealed a paradoxical slight increase in brain natriuretic peptide in the dapagliflozin arm. The authors attributed this potentially to increased erythropoietin, which has been linked to elevated
dapagliflozin 22453 triglycerides were mildly reduced under SGLT2 inhibition. LDL was increased from 1.8% to 4.4% with dapagliflozin versus 0.4% with placebo. Triglycerides were slightly reduced by –2.4% to –6.2% and by 2.1% with
dapagliflozin 22568 versus 0.4% with placebo. Triglycerides were slightly reduced by –2.4% to –6.2% and by 2.1% with dapagliflozin and placebo, respectively.[53] It is unclear if these small perturbations are clinically relevant.[54]
dapagliflozin 25151 and fracture riskIn a randomized, double-blind study, 252 patients were assigned to either low-dose dapagliflozin , high-dose dapagliflozin, or placebo. It was found that 13 patients receiving dapagliflozin incurred
dapagliflozin 25176 randomized, double-blind study, 252 patients were assigned to either low-dose dapagliflozin, high-dose dapagliflozin , or placebo. It was found that 13 patients receiving dapagliflozin incurred a bone fracture, whereas
dapagliflozin 25243 low-dose dapagliflozin, high-dose dapagliflozin, or placebo. It was found that 13 patients receiving dapagliflozin incurred a bone fracture, whereas no patients receiving placebo experienced a bone fracture.[58] Seven
dapagliflozin 26120 respectively. These changes occurred while taking SGLT2 inhibitors at expected pharmacological dosing. Both dapagliflozin and canagliflozin have been shown to increase levels of bone formation biomarkers, corroborating increased
metformin 3965 loss and exercise feature prominently.[10] Among the pharmaceutical approaches other than insulin, metformin has been consistently recommended as a useful agent in T2DM in part because it does not promote weight
metformin 9908 glycated HbA1C compared with placebo on the order of 0.9–1.2%.[20],[21] When used in combination with metformin , the reductions in HbA1C are typically ~0.6%. When used with metformin and a sulfonylurea, reductions
metformin 9979 When used in combination with metformin, the reductions in HbA1C are typically ~0.6%. When used with metformin and a sulfonylurea, reductions of ~0.7% are noted. The combination of canagliflozin to metformin plus
metformin 10076 with metformin and a sulfonylurea, reductions of ~0.7% are noted. The combination of canagliflozin to metformin plus thiazolidinedione is attended by ~0.9% HbA1C reduction.[22]–[25] Compared with glimepiride, reductions
metformin 10297 in HbA1C with canagliflozin add-on therapy (decrease of 0.8–0.9%) in patients already treated with metformin were similar to glimepiride (decrease of 0.8%) at 52 weeks.[26] These changes in HbA1C remained persistent
metformin 10456 52 weeks.[26] These changes in HbA1C remained persistent for 2 years.[27] In patients treated with metformin plus a sulfonylurea, reductions in HbA1C with 300 mg canagliflozin daily (1.0%) were similar to sitagliptin
metformin 16150 reduces urinary albumin excretion compared with other antihyperglycemics in diabetic patients already on metformin .[42] The magnitude of urine ACR reduction appears to be time dependent and is ~25% after 1 year, dropping
metformin 40617 http://www.tandfonline.com).[70]Abbreviations: CANA, canagliflozin; GLIM, glimepiride; PBO, placebo; SITA, sitagliptin; MET, metformin ; SU, sulfonylurea; NA, not applicable; NT, not tested; PIO, pioglitazone; A1C%, Hemoglobin A1C concentration.Table
pioglitazone 40687 placebo; SITA, sitagliptin; MET, metformin; SU, sulfonylurea; NA, not applicable; NT, not tested; PIO, pioglitazone ; A1C%, Hemoglobin A1C concentration.Table 2Major ongoing trials using canagliflozinAge (years)Treatment
sitagliptin 10562 metformin plus a sulfonylurea, reductions in HbA1C with 300 mg canagliflozin daily (1.0%) were similar to sitagliptin (0.7%) at 52 weeks.[28] As monotherapy, or in combination regimens, canagliflozin is an effective antihyperglycemic
sitagliptin 23713 colonization, and of those who were initially negative, 31% of canagliflozin cohort and 14% of the placebo/ sitagliptin subjects had conversion to positive urine tests by week 12 (odds ratio [OR], 2.8; 95% CI, 1.0–7.3
sitagliptin 23854 positive urine tests by week 12 (odds ratio [OR], 2.8; 95% CI, 1.0–7.3 for canagliflozin vs placebo/ sitagliptin ). This conversion placed subjects at increased risk for VVAEs, including candidiasis, cervicitis, furuncle,
sitagliptin 24120 candidiasis, vulvovaginal mycotic infection, vulvovaginal pruritus, and vulvovaginitis. Two placebo/ sitagliptin (3%) and 16 canagliflozin subjects (10%) experienced VVAE. Notably, these infections did not require
sitagliptin 40599 http://www.tandfonline.com).[70]Abbreviations: CANA, canagliflozin; GLIM, glimepiride; PBO, placebo; SITA, sitagliptin ; MET, metformin; SU, sulfonylurea; NA, not applicable; NT, not tested; PIO, pioglitazone; A1C%, Hemoglobin
Select Disease Character Offset Disease Term Instance
Fanconi syndrome 6447 excessive urinary excretion of amino acids, phosphate, bicarbonate, and other solutes, the diagnosis of Fanconi syndrome is likely present. If glucosuria is isolated, without hyperglycemia, this corroborates familial renal
diabetes mellitus 474 USAPublication date (collection): /2017Publication date (epub): 2/2017AbstractCaring for patients with type 2 diabetes mellitus (T2DM) has entered an era with many recent additions to the regimens used to clinically control their
diabetes mellitus 2101 this new group of antidiabetic agents.BackgroundScope of problems in managing the patients with type 2 diabetes mellitus (T2DM)The obesity epidemic has had multiple effects on public health, including an increase in blood
diabetes mellitus 26691 In one review of 13 patients by Peters et al,[62] they described the complication in 7 with type 1 diabetes mellitus and two with T2DM. The altered physiology under SGLT2 inhibition can explain this via several mechanisms.
diabetes mellitus 36276 requiring participants to be in the age group of ≥50 years and to have two of the following: duration of diabetes mellitus (DM) for >10 years; SBP >140 mmHg or at least one BP medication; current smoker; albuminuria above normal
diabetic ketoacidosis 22007 the placebo group.[49] Significant acute kidney injury seems to occur during episodes of euglycemic diabetic ketoacidosis (DKA), which are less common events. This suggests that the risk of acute kidney injury is minimal under
hyperglycemia 594 (T2DM) has entered an era with many recent additions to the regimens used to clinically control their hyperglycemia . The most recent class of agents approved by the Food and Drug Administration (FDA) for T2DM is the
hyperglycemia 3522 diagnosis of diabetes.[8] Such findings support the clinical concept that tissue damage associated with hyperglycemia develops before the clinical symptoms and signs are manifest.[9]Evolution of therapies for diabetesThe
hyperglycemia 3653 the clinical symptoms and signs are manifest.[9]Evolution of therapies for diabetesThe management of hyperglycemia in diabetic patients has fostered the development of an impressive array of lifestyle and pharmaceutical
hyperglycemia 6518 other solutes, the diagnosis of Fanconi syndrome is likely present. If glucosuria is isolated, without hyperglycemia , this corroborates familial renal glucosuria (FRG) as the diagnosis. FRG is linked to mutation in the
hyperglycemia 14615 treated with phlorizin revealed improved antioxidant enzyme activity and attenuated end effects of hyperglycemia . Diabetes is associated with increased tyrosine nitration in the renal cortex and medulla. Nitrotyrosine
hyperglycemia 27165 concerning phenomena with euglycemic DKA is the uncoupling of the clinical presentation from symptoms of hyperglycemia . Only 32% of the patients reviewed by Peters et al presented with vomiting. Thus, these patients are
hyperphosphatemia 25780 which increases cotransport of sodium and phosphate through their respective protein. This leads to hyperphosphatemia and subsequently increased parathyroid hormone levels.[60] The effects on 1,25-dihydroxyvitamin D is
hypoglycemia 4086 consistently recommended as a useful agent in T2DM in part because it does not promote weight gain or hypoglycemia , unlike sulfonylurea agents and insulin, which typically do.[11] In recent years, a number of new classes
hypoglycemia 17322 important to cast a wide net in this section and cover the entire class.HypoglycemiaAlthough the risk of hypoglycemia with SGLT2 inhibitors is greater than placebo,[46] it is in fact lower when compared with sulfonylureas.
hypoglycemia 17484 placebo,[46] it is in fact lower when compared with sulfonylureas. Dapagliflozin was found to have episodes of hypoglycemia at a rate of 11.8%, which was marginally increased over placebo at 7.0%.[47] Protection from significant
hypoglycemia 17602 rate of 11.8%, which was marginally increased over placebo at 7.0%.[47] Protection from significant hypoglycemia occurs secondary to the insulin-independent mechanism of SGLT2 inhibitors, hepatic gluconeogenesis,
hypoglycemia 18092 between placebo and empagliflozin at different doses and that empagliflozin in fact had less incidence of hypoglycemia requiring assistance.[49] Overall, episodes of hypoglycemia occur at a similar rate as placebo and should
hypoglycemia 18152 empagliflozin in fact had less incidence of hypoglycemia requiring assistance.[49] Overall, episodes of hypoglycemia occur at a similar rate as placebo and should not limit the use of SGLT2 inhibitors.Interestingly, recent
hypoglycemia 18551 provides another compelling argument for the therapeutic potency of SGLT2 inhibitors.[50]The risk of hypoglycemia is increased when SGLT2 inhibitors are combined with hypoglycemic agents (sulfonylureas or insulin)
hypoglycemia 24897 fastidious bathroom habits, and do not outweigh the significant improvements in glucose control without hypoglycemia . In addition, one can further minimize infection risks by advising patients to drink more fluids –
obesity 2129 agents.BackgroundScope of problems in managing the patients with type 2 diabetes mellitus (T2DM)The obesity epidemic has had multiple effects on public health, including an increase in blood pressure (BP) and
renal glycosuria 8892 such as canagliflozin, did not affect amino acid excretion and appeared to model a disorder known as renal glycosuria , an autosomal dominant heritable condition.[15]Clinical profile of canagliflozinClinical effects of
type 1 diabetes mellitus 26684 inhibitor use. In one review of 13 patients by Peters et al,[62] they described the complication in 7 with type 1 diabetes mellitus and two with T2DM. The altered physiology under SGLT2 inhibition can explain this via several mechanisms.
type 2 diabetes mellitus 467 USAPublication date (collection): /2017Publication date (epub): 2/2017AbstractCaring for patients with type 2 diabetes mellitus (T2DM) has entered an era with many recent additions to the regimens used to clinically control their
type 2 diabetes mellitus 2094 of this new group of antidiabetic agents.BackgroundScope of problems in managing the patients with type 2 diabetes mellitus (T2DM)The obesity epidemic has had multiple effects on public health, including an increase in blood

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