Baseline characteristics of participants enrolled in the empagliflozin cardiovascular outcome trial (EMPA-REG OUTCOME™) in patients with type 2 diabetes

Zinman, B.; Inzucchi, Silvio E.; Lachin, John M.; Wanner, Christoph; Ferrari, Roberto; Fitchett, David; Bluhmki, Erich; Kempthorne‐Rawson, Joan; Newman, Julie; Johansen, OE; Woerle, HJ; Broedl, UC

doi:10.1055/s-0034-1374995

Cited by 8 publications

(9 citation statements)

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“…The changes in fasting LDL and HDL cholesterol are similar to those recently reported in the BI 10773 (Empagliflozin) Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients (EMPA-REG OUTCOME) trial (13), which showed a significant reduction in incident major cardiovascular disease outcomes.…”

Section: Discussionsupporting

confidence: 84%

Shift to Fatty Substrate Utilization in Response to Sodium–Glucose Cotransporter 2 Inhibition in Subjects Without Diabetes and Patients With Type 2 Diabetes

et al. 2016

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Pharmacologically induced glycosuria elicits adaptive responses in glucose homeostasis and hormone release. In type 2 diabetes (T2D), along with decrements in plasma glucose and insulin levels and increments in glucagon release, sodium-glucose cotransporter 2 (SGLT2) inhibitors induce stimulation of endogenous glucose production (EGP) and a suppression of tissue glucose disposal (TGD). We measured fasting and postmeal glucose fluxes in 25 subjects without diabetes using a double glucose tracer technique; in these subjects and in 66 previously reported patients with T2D, we also estimated lipolysis (from [ 2 H 5 ]glycerol turnover rate and circulating free fatty acids, glycerol, and triglycerides), lipid oxidation (LOx; by indirect calorimetry), and ketogenesis (from circulating b-hydroxybutyrate concentrations). In both groups, empagliflozin administration raised EGP, lowered TGD, and stimulated lipolysis, LOx, and ketogenesis. The pattern of glycosuria-induced changes was similar in subjects without diabetes and in those with T2D but quantitatively smaller in the former. With chronic (4 weeks) versus acute (first dose) drug administration, glucose flux responses were attenuated, whereas lipid responses were enhanced; in patients with T2D, fasting b-hydroxybutyrate levels rose from 246 6 288 to 561 6 596 mmol/L (P < 0.01). We conclude that by shunting substantial amounts of carbohydrate into urine, SGLT2-mediated glycosuria results in a progressive shift in fuel utilization toward fatty substrates. The associated hormonal milieu (lower insulin-to-glucagon ratio) favors glucose release and ketogenesis.When large quantities of glucose are pharmacologically forced into urinary excretion, whole-body metabolism undergoes adaptive changes involving glucose fluxes, hormonal responses, fuel selection, and energy expenditure (1,2). In previous work (3), we used empagliflozin to investigate the physiological response to forced glycosuria in patients with type 2 diabetes (T2D). By combining a mixed meal with the double-tracer technique, we found that after acute or chronic empagliflozin administration endogenous glucose production (EGP) rose, tissue glucose disposal (TGD) decreased, and lipid utilization increased. The aims of the present work were to measure the full spectrum of changes in lipolysis, lipid levels, and substrate availability consequent upon empagliflozininduced glycosuria in patients with T2D and to test whether and to what extent these changes occur in subjects without diabetes. RESEARCH DESIGN AND METHODS PopulationSixty-six patients with T2D were recruited into the study; their inclusion criteria are detailed in Ferrannini et al. (3). Twenty-five subjects without diabetes (12 with normal glucose tolerance [NGT] and 13 with impaired glucose tolerance [IGT]) served as control subjects (Supplementary Table 1). The glucose and hormone data for the patients with T2D have been reported (3) and are repeated here for comparison purposes. The study (clinicaltrials.gov identifier NCT01248364; EudraCT number 2010-...

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Section: Discussionsupporting

confidence: 84%

Shift to Fatty Substrate Utilization in Response to Sodium–Glucose Cotransporter 2 Inhibition in Subjects Without Diabetes and Patients With Type 2 Diabetes

et al. 2016

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“…(9,14) In our study, with a relatively small sample size, there was no significant change in LDL-cholesterol from baseline in the canagliflozin 300 mg group.…”

Section: Discussioncontrasting

confidence: 54%

“…(7) In the recently published EMPA-REG study, empagliflozin, an SGLT2 inhibitor, has also been shown to reduce cardiovascular mortality in patients with T2DM at high risk for cardiovascular events. (9) In a more recent publication from the same study, it was reported that empagliflozin was associated with slower progression of kidney disease and lower rates of clinically relevant renal events than placebo when added to standard care. (10) Canagliflozin, the first US Food and Drug Administration (FDA)-approved SGLT2…”

Section: Introductionmentioning

confidence: 99%

Short-term outcomes of patients with Type 2 diabetes mellitus treated with canagliflozin compared with sitagliptin in a real-world setting

Shao

Yee

Koh

et al. 2018

smedj

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“…However, it has been reported that transient increase in urine volume without a change in hematocrit was also observed after initiation of canagliflozin 19 . The mechanism of the increase in hematocrit when using SGLT2 inhibitors is unclear 20 , and there is also no strong relationship to an elevation in risk of CV events 21 . The relationship between CV events, such as cerebral infarction or myocardial infarction, and hydration was also unclear in this PMS.…”

Section: Discussionmentioning

confidence: 99%

Safety and efficacy of canagliflozin in elderly patients with type 2 diabetes mellitus: a 1-year post-marketing surveillance in Japan

Goda

Yamakura

Sasaki

et al. 2017

Current Medical Research and Opinion

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Objective: To evaluate the safety and efficacy of canagliflozin in elderly patients with type 2 diabetes mellitus (T2DM) in clinical settings. Methods: The authors conducted a 1-year post-marketing surveillance (PMS) of canagliflozin in almost all the elderly patients (!65 years old) with T2DM who began taking canagliflozin during the first 3 months after its launch in Japan. The main outcomes included the incidences of adverse drug reactions (ADRs), serious ADRs, and the changes of laboratory tests as well as efficacy variables. Results: An ADR was reported in 9.09% (125 of 1375 patients) in the safety analysis set. The main ADRs were dehydration, constipation, thirst, pollakiuria, dizziness, cystitis, eczema, pruritus, and rash. The incidence of serious ADRs was 1.02% (14 patients), which included urinary tract infection, dehydration, hypoglycemia, and cerebral infarction (two patients each). ADRs of special interest that had been reported in clinical trials of SGLT2 inhibitors, such as hypoglycemia, volume depletion-related events, genital/urinary tract infection, polyuria/pollakiuria, and ketone body increased were also observed in this PMS. The safety profiles were similar to the results of a previous clinical study of canagliflozin, and new safety concerns were not identified in this survey. The mean change in HbA1c was -0.77% after 12 months of treatment in the efficacy analysis set. Conclusion: In this PMS, the safety and efficacy profiles of canagliflozin in elderly patients with T2DM were obtained in the clinical settings in Japan and the drug was well tolerated and effective in improving glycemic control. ARTICLE HISTORY

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Baseline characteristics of participants enrolled in the empagliflozin cardiovascular outcome trial (EMPA-REG OUTCOME™) in patients with type 2 diabetes

Cited by 8 publications

References 0 publications

Shift to Fatty Substrate Utilization in Response to Sodium–Glucose Cotransporter 2 Inhibition in Subjects Without Diabetes and Patients With Type 2 Diabetes

Shift to Fatty Substrate Utilization in Response to Sodium–Glucose Cotransporter 2 Inhibition in Subjects Without Diabetes and Patients With Type 2 Diabetes

Short-term outcomes of patients with Type 2 diabetes mellitus treated with canagliflozin compared with sitagliptin in a real-world setting

Safety and efficacy of canagliflozin in elderly patients with type 2 diabetes mellitus: a 1-year post-marketing surveillance in Japan

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