23 results on '"Gause-Nilsson, Ingrid A. M."'
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2. Effects of dapagliflozin on development and progression of kidney disease in patients with type 2 diabetes: an analysis from the DECLARE–TIMI 58 randomised trial
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Mosenzon, Ofri, Wiviott, Stephen D, Cahn, Avivit, Rozenberg, Aliza, Yanuv, Ilan, Goodrich, Erica L, Murphy, Sabina A, Heerspink, Hiddo J L, Zelniker, Thomas A, Dwyer, Jamie P, Bhatt, Deepak L, Leiter, Lawrence A, McGuire, Darren K, Wilding, John P H, Kato, Eri T, Gause-Nilsson, Ingrid A M, Fredriksson, Martin, Johansson, Peter A, Langkilde, Anna Maria, Sabatine, Marc S, and Raz, Itamar
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- 2019
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3. Efficacy and Safety of Dapagliflozin According to Background Use of Cardiovascular Medications in Patients With Type 2 Diabetes
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Oyama, Kazuma, primary, Raz, Itamar, additional, Cahn, Avivit, additional, Goodrich, Erica L., additional, Bhatt, Deepak L., additional, Leiter, Lawrence A., additional, McGuire, Darren K., additional, Wilding, John P. H., additional, Gause-Nilsson, Ingrid A. M., additional, Mosenzon, Ofri, additional, Sabatine, Marc S., additional, and Wiviott, Stephen D., additional
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- 2022
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4. Association of Baseline HbA1c With Cardiovascular and Renal Outcomes: Analyses From DECLARE-TIMI 58
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Cahn, Avivit, primary, Wiviott, Stephen D., primary, Mosenzon, Ofri, primary, Murphy, Sabina A., primary, Goodrich, Erica L., primary, Yanuv, Ilan, primary, Rozenberg, Aliza, primary, Bhatt, Deepak L., primary, Leiter, Lawrence A., primary, McGuire, Darren K., primary, Wilding, John P.H., primary, Gause-Nilsson, Ingrid A. M., primary, Langkilde, Anna Maria, primary, Sabatine, Marc S., primary, and Raz, Itamar, primary
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- 2022
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5. Obesity and effects of dapagliflozin on cardiovascular and renal outcomes in patients with type 2 diabetes mellitus in the DECLARE–TIMI 58 trial
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Oyama, Kazuma, primary, Raz, Itamar, additional, Cahn, Avivit, additional, Kuder, Julia, additional, Murphy, Sabina A, additional, Bhatt, Deepak L, additional, Leiter, Lawrence A, additional, McGuire, Darren K, additional, Wilding, John P H, additional, Park, Kyong Soo, additional, Goudev, Assen, additional, Diaz, Rafael, additional, Špinar, Jindřich, additional, Gause-Nilsson, Ingrid A M, additional, Mosenzon, Ofri, additional, Sabatine, Marc S, additional, and Wiviott, Stephen D, additional
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- 2021
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6. The Effect of Dapagliflozin on Albuminuria in DECLARE-TIMI 58
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Mosenzon, Ofri, primary, Wiviott, Stephen D, primary, Heerspink, Hiddo H J, primary, Dwyer, Jamie P, primary, Cahn, Avivit, primary, Goodrich, Erica L, primary, Rozenberg, Aliza, primary, Schechter, Meir, primary, Yanuv, Ilan, primary, Murphy, Sabina A, primary, Zelniker, Thomas A, primary, Gause-Nilsson, Ingrid A M, primary, Langkilde, Anna Maria, primary, Fredriksson, Martin, primary, Johansson, Peter A, primary, Bhatt, Deepak L, primary, Leiter, Lawrence A, primary, McGuire, Darren K, primary, Wilding, John P H, primary, Sabatine, Marc S, primary, and Raz, Itamar, primary
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- 2021
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7. Obesity and effects of dapagliflozin on cardiovascular and renal outcomes in patients with type 2 diabetes mellitus in the DECLARE–TIMI 58 trial.
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Oyama, Kazuma, Raz, Itamar, Cahn, Avivit, Kuder, Julia, Murphy, Sabina A, Bhatt, Deepak L, Leiter, Lawrence A, McGuire, Darren K, Wilding, John P H, Park, Kyong Soo, Goudev, Assen, Diaz, Rafael, Špinar, Jindřich, Gause-Nilsson, Ingrid A M, Mosenzon, Ofri, Sabatine, Marc S, and Wiviott, Stephen D
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TYPE 2 diabetes ,SODIUM-glucose cotransporter 2 inhibitors ,DAPAGLIFLOZIN ,ATRIAL flutter ,DISEASE risk factors - Abstract
Aims We investigated the associations between obesity, cardiorenal events, and benefits of dapagliflozin in patients with type 2 diabetes mellitus (T2DM). Methods and results DECLARE–TIMI 58 randomized patients with T2DM and either atherosclerotic cardiovascular (CV) disease or multiple risk factors to dapagliflozin vs. placebo. Patients were stratified by body mass index (BMI, kg/m
2 ): normal (18.5 to <25), overweight (25 to <30), moderately obese (30 to <35), severely obese (35 to <40), and very-severely obese (≥40). Outcomes analysed were CV death, hospitalization for heart failure (HHF), renal-specific composite outcome, and atrial fibrillation or flutter (AF/AFL). Of 17 134 patients, 9.0% had a normal BMI, 31.5% were overweight, 32.4% were moderately, 17.2% severely, and 9.8% were very-severely obese. Higher BMI was associated with a higher adjusted risk of HHF and AF/AFL (hazard ratio 1.30 and 1.28, respectively, per 5 kg/m2 ; P < 0.001 for all). Dapagliflozin reduced body weight by similar relative amounts consistently across BMI categories (percent difference: −1.9 to −2.4%). Although relative risk reductions in CV and renal-specific composite outcomes with dapagliflozin did not significantly differ across the range of BMI (P for interaction ≥0.20 for all outcomes), obese patients (BMI ≥ 30 kg/m2 ) tended to derive greater absolute risk reduction in HHF and AF/AFL (P for interaction 0.02 and 0.09, respectively) than non-obese patients. Conclusions In DECLARE–TIMI 58, patients with T2DM and higher BMI were more likely to have HHF and AF/AFL. Whereas relative risk reductions in CV and renal outcomes with dapagliflozin were generally consistent across the range of BMI, absolute risk reduction in obesity-related outcomes including HHF and AF/AFL tended to be larger in obese patients with T2DM. Clinical trial registration URL: https://www.clinicaltrials.gov. Unique identifiers: NCT01730534. [ABSTRACT FROM AUTHOR]- Published
- 2022
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8. Association of Baseline HbA1c With Cardiovascular and Renal Outcomes: Analyses From DECLARE-TIMI 58.
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Cahn, Avivit, Wiviott, Stephen D., Mosenzon, Ofri, Goodrich, Erica L., Murphy, Sabina A., Yanuv, Ilan, Rozenberg, Aliza, Bhatt, Deepak L., Leiter, Lawrence A., McGuire, Darren K., Wilding, John P. H., Gause-Nilsson, Ingrid A. M., Langkilde, Anna Maria, Sabatine, Marc S., and Raz, Itamar
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BENZENE ,RESEARCH ,RESEARCH methodology ,CARDIOVASCULAR diseases ,EVALUATION research ,TYPE 2 diabetes ,CARDIOVASCULAR system ,COMPARATIVE studies ,HEART failure ,DISEASE complications - Abstract
Objective: Current guidelines recommend prescribing SGLT2 inhibitors to patients with type 2 diabetes and established or at high risk for atherosclerotic cardiovascular disease (ASCVD), irrespective of HbA1c levels. We studied the association of HbA1c with cardiovascular and renal outcomes and whether the benefit of dapagliflozin varies by baseline HbA1c.Research Design and Methods: In the Dapagliflozin Effect on Cardiovascular Events trial (DECLARE-TIMI 58), 17,160 patients with type 2 diabetes were randomly assigned to dapagliflozin or placebo for a median follow-up of 4.2 years. Cardiovascular and renal outcomes by baseline HbA1c in the overall population and with dapagliflozin versus placebo in HbA1c subgroups were studied by Cox regression models.Results: In the overall population, higher baseline HbA1c was associated with a higher risk of cardiovascular death or hospitalization for heart failure (HHF); major adverse cardiovascular events (MACE), including cardiovascular death, myocardial infarction, and ischemic stroke; and cardiorenal outcomes (adjusted hazard ratios 1.12 [95% CI 1.06-1.19], 1.08 [1.04-1.13], and 1.17 [1.11-1.24] per 1% higher level, respectively). Elevated HbA1c was associated with a greater increased risk for MACE and cardiorenal outcomes in patients with multiple risk factors (MRF) than in established ASCVD (P-interaction = 0.0064 and 0.0093, respectively). Compared with placebo, dapagliflozin decreased the risk of cardiovascular death/HHF, HHF, and cardiorenal outcomes, with no heterogeneity by baseline HbA1c (P-interaction > 0.05).Conclusions: Higher HbA1c levels were associated with greater cardiovascular and renal risk, particularly in the MRF population, yet the benefits of dapagliflozin were observed in all subgroups irrespective of baseline HbA1c, including patients with HbA1c <7%. [ABSTRACT FROM AUTHOR]- Published
- 2022
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9. Cardiovascular, Renal, and Metabolic Outcomes of Dapagliflozin Versus Placebo in a Primary Cardiovascular Prevention Cohort: Analyses From DECLARE-TIMI 58
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Cahn, Avivit, primary, Raz, Itamar, primary, Leiter, Lawrence A., primary, Mosenzon, Ofri, primary, Murphy, Sabina A., primary, Goodrich, Erica L., primary, Yanuv, Ilan, primary, Rozenberg, Aliza, primary, Bhatt, Deepak L., primary, McGuire, Darren K., primary, Wilding, John P.H., primary, Gause-Nilsson, Ingrid A. M., primary, Langkilde, Anna Maria, primary, Sabatine, Marc S., primary, and Wiviott, Stephen D., primary
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- 2021
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10. Cardiorenal outcomes with dapagliflozin by baseline glucose‐lowering agents: Post hoc analyses from DECLARE‐TIMI 58
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Cahn, Avivit, primary, Wiviott, Stephen D., additional, Mosenzon, Ofri, additional, Murphy, Sabina A., additional, Goodrich, Erica L., additional, Yanuv, Ilan, additional, Rozenberg, Aliza, additional, Wilding, John P. H., additional, Leiter, Lawrence A., additional, Bhatt, Deepak L., additional, McGuire, Darren K., additional, Litwak, Leon, additional, Kooy, Adriaan, additional, Gause‐Nilsson, Ingrid A. M., additional, Fredriksson, Martin, additional, Langkilde, Anna Maria, additional, Sabatine, Marc S., additional, and Raz, Itamar, additional
- Published
- 2020
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11. Safety of dapagliflozin in a broad population of patients with type 2 diabetes: Analyses from the DECLARE‐TIMI 58 study
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Cahn, Avivit, primary, Raz, Itamar, additional, Bonaca, Marc, additional, Mosenzon, Ofri, additional, Murphy, Sabina A., additional, Yanuv, Ilan, additional, Rozenberg, Aliza, additional, Wilding, John P. H., additional, Bhatt, Deepak L., additional, McGuire, Darren K., additional, Gause‐Nilsson, Ingrid A. M., additional, Fredriksson, Martin, additional, Johansson, Peter A., additional, Jermendy, Gyorgy, additional, Hadjadj, Samy, additional, Langkilde, Anna Maria, additional, Sabatine, Marc S., additional, Wiviott, Stephen D., additional, and Leiter, Lawrence A., additional
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- 2020
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12. Cardiovascular and renal benefits of dapagliflozin in patients with short and long‐standing type 2 diabetes: Analysis from the DECLARE‐TIMI 58 trial
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Bajaj, Harpreet S., primary, Raz, Itamar, additional, Mosenzon, Ofri, additional, Murphy, Sabina A., additional, Rozenberg, Aliza, additional, Yanuv, Ilan, additional, Bhatt, Deepak L., additional, Leiter, Lawrence A., additional, McGuire, Darren K., additional, Wilding, John P. H., additional, Gause‐Nilsson, Ingrid A. M., additional, Sabatine, Marc S., additional, Wiviott, Stephen D., additional, and Cahn, Avivit, additional
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- 2020
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13. Cardiorenal outcomes with dapagliflozin by baseline glucose‐lowering agents: Post hoc analyses from DECLARE‐TIMI 58.
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Cahn, Avivit, Wiviott, Stephen D., Mosenzon, Ofri, Murphy, Sabina A., Goodrich, Erica L., Yanuv, Ilan, Rozenberg, Aliza, Wilding, John P. H., Leiter, Lawrence A., Bhatt, Deepak L., McGuire, Darren K., Litwak, Leon, Kooy, Adriaan, Gause‐Nilsson, Ingrid A. M., Fredriksson, Martin, Langkilde, Anna Maria, Sabatine, Marc S., and Raz, Itamar
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DAPAGLIFLOZIN ,EXENATIDE ,GLUCAGON-like peptide-1 receptor ,TYPE 2 diabetes ,GLUCAGON-like peptide-1 agonists ,MYOCARDIAL infarction ,CARDIOVASCULAR disease related mortality - Abstract
Aim: To assess the associations between baseline glucose‐lowering agents (GLAs) and cardiorenal outcomes with dapagliflozin versus placebo in the DECLARE‐TIMI 58 study. Materials and methods: DECLARE‐TIMI 58 assessed the cardiorenal outcomes of dapagliflozin versus placebo in patients with type 2 diabetes. This post hoc analysis elaborates the efficacy and safety outcomes by baseline GLA for treatment effect and GLA‐based treatment interaction. Results: At baseline, 14 068 patients (82.0%) used metformin, 7322 (42.7%) sulphonylureas, 2888 (16.8%) dipeptidyl peptidase‐4 inhibitors, 750 (4.4%) glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs) and 7013 (40.9%) insulin. Dapagliflozin reduced the composite of cardiovascular death (CVD) and hospitalization for heart failure (HHF) versus placebo regardless of baseline GLA, with greater benefit in the small group of patients with baseline use of GLP‐1 RAs (HR [95% CI] 0.37 [0.18, 0.78] vs. 0.86 [0.75, 0.98] in GLP‐1 RA users vs. non‐users, Pinteraction =.03). The overall HR for major adverse cardiovascular events (CVD, myocardial infarction or ischaemic stroke) was 0.93 (95% CI 0.84, 1.03) with dapagliflozin versus placebo, with no interaction by baseline GLA (Pinteraction >.05). The renal‐specific outcome was reduced with dapagliflozin versus placebo in the overall cohort (HR [95%CI] 0.53[0.43‐0.66]), with no interaction by baseline GLA (Pinteraction >.05). All of these outcomes were similar in those with versus those without baseline metformin use. Conclusions: The effects of dapagliflozin on cardiorenal outcomes were generally consistent regardless of baseline GLA, with consistent benefits regardless of baseline metformin use. The potential clinical benefit of combining sodium‐glucose co‐transporter‐2 inhibitors with GLP‐1 RAs, given some evidence of cardiovascular risk reduction with both classes, should be explored further. [ABSTRACT FROM AUTHOR]
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- 2021
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14. Efficacy and Safety of Dapagliflozin in the Elderly: Analysis From the DECLARE-TIMI 58 Study.
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Cahn, Avivit, Mosenzon, Ofri, Wiviott, Stephen D., Rozenberg, Aliza, Yanuv, Ilan, Goodrich, Erica L., Murphy, Sabina A., Bhatt, Deepak L., Leiter, Lawrence A., McGuire, Darren K., Wilding, John P. H., Gause-Nilsson, Ingrid A. M., Fredriksson, Martin, Johansson, Peter A., Langkilde, Anna Maria, Sabatine, Marc S., and Raz, Itamar
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DAPAGLIFLOZIN ,URINARY tract infections ,DIABETIC acidosis ,ACUTE kidney failure ,TREATMENT effectiveness - Abstract
Objective: Data regarding the effects of sodium-glucose cotransporter 2 inhibitors in the elderly (age ≥65 years) and very elderly (age ≥75 years) are limited.Research Design and Methods: The Dapagliflozin Effect on Cardiovascular Events (DECLARE)-TIMI 58 assessed cardiac and renal outcomes of dapagliflozin versus placebo in patients with type 2 diabetes. Efficacy and safety outcomes were studied within age subgroups for treatment effect and age-based treatment interaction.Results: Of the 17,160 patients, 9,253 were <65 years of age, 6,811 ≥65 to <75 years, and 1,096 ≥75 years. Dapagliflozin reduced the composite of cardiovascular death or hospitalization for heart failure consistently, with a hazard ratio (HR) of 0.88 (95% CI 0.72, 1.07), 0.77 (0.63, 0.94), and 0.94 (0.65, 1.36) in age-groups <65, ≥65 to <75, and ≥75 years, respectively (interaction P value 0.5277). Overall, dapagliflozin did not significantly decrease the rates of major adverse cardiovascular events, with HR 0.93 (95% CI 0.81, 1.08), 0.97 (0.83, 1.13), and 0.84 (0.61, 1.15) in age-groups <65, ≥65 to <75, and ≥75 years, respectively (interaction P value 0.7352). The relative risk reduction for the secondary prespecified cardiorenal composite outcome ranged from 18% to 28% in the different age-groups with no heterogeneity. Major hypoglycemia was less frequent with dapagliflozin versus placebo, with HR 0.97 (95% CI 0.58, 1.64), 0.50 (0.29, 0.84), and 0.68 (0.29, 1.57) in age-groups <65, ≥65 to <75, and ≥75 years, respectively (interaction P value 0.2107). Safety outcomes, including fractures, volume depletion, cancer, urinary tract infections, and amputations were balanced with dapagliflozin versus placebo, and acute kidney injury was reduced, all regardless of age. Genital infections that were serious or led to discontinuation of the study drug and diabetic ketoacidosis were uncommon, yet more frequent with dapagliflozin versus placebo, without heterogeneity (interaction P values 0.1058 and 0.8433, respectively).Conclusions: The overall efficacy and safety of dapagliflozin are consistent regardless of age. [ABSTRACT FROM AUTHOR]- Published
- 2020
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15. DECLARE‐TIMI 58: Participants’ baseline characteristics
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Raz, Itamar, primary, Mosenzon, Ofri, additional, Bonaca, Marc P., additional, Cahn, Avivit, additional, Kato, Eri T., additional, Silverman, Michael G., additional, Bhatt, Deepak L., additional, Leiter, Lawrence A., additional, McGuire, Darren K., additional, Wilding, John P. H., additional, Gause‐Nilsson, Ingrid A. M., additional, Langkilde, Anna M., additional, Johansson, Peter A., additional, Sabatine, Marc S., additional, and Wiviott, Stephen D., additional
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- 2018
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16. Efficacy and Safety of Dapagliflozin by Baseline Insulin Regimen and Dose: Post Hoc Analyses From DECLARE-TIMI 58.
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Pollack R, Raz I, Wiviott SD, Goodrich EL, Murphy SA, Yanuv I, Rozenberg A, Mosenzon O, Langkilde AM, Gause-Nilsson IAM, Bhatt DL, Leiter LA, McGuire DK, Wilding JPH, Sabatine MS, and Cahn A
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- Humans, Insulin therapeutic use, Glucosides adverse effects, Benzhydryl Compounds adverse effects, Insulin, Regular, Human therapeutic use, Diabetes Mellitus, Type 2, Sodium-Glucose Transporter 2 Inhibitors therapeutic use
- Abstract
Objective: The cardiorenal benefits of adding sodium-glucose cotransporter 2 (SGLT2) inhibitor therapy for patients on insulin, particularly those on intensive regimens that include short-acting (SA) insulin, have not been explored., Research Design and Methods: In Dapagliflozin Effect on Cardiovascular Events trial (DECLARE-TIMI 58), 17,160 patients with type 2 diabetes were randomized to dapagliflozin or placebo for a median follow-up of 4.2 years. Cardiovascular (CV), renal, metabolic, and safety outcomes with dapagliflozin versus placebo by insulin dose and regimen were studied with Cox regression models., Results: The study included 7,013 insulin users at baseline, with 4,650 (66.3%) patients on regimens including SA insulin. Insulin doses varied, with 2,443 (34.8%) patients receiving <0.5 IU/kg, 2,795 (39.9%) 0.5 to ≤1 IU/kg, and 1,339 (19.1%) >1 IU/kg. Dapagliflozin reduced CV death/hospitalization for heart failure among overall insulin users (hazard ratio [HR] 0.82 [95% CI 0.69-0.97]) and consistently in patients on insulin regimens with or without SA insulin (0.83 [0.67-1.03] and 0.78 [0.57-1.07], respectively, Pinteraction = 0.75). No heterogeneity was observed by insulin dose (Pinteraction = 0.43). The HR for major adverse CV events with dapagliflozin among insulin users (0.84 [0.74-0.97]) was similar irrespective of regimen or dose (Pinteraction = 0.75 and 0.07). Dapagliflozin reduced the rate of adverse renal outcomes overall and consistently across subgroups of insulin users. Decreases in HbA1c, weight, and systolic blood pressure with dapagliflozin were seen regardless of insulin dose or regimen. The known safety profile of dapagliflozin was unchanged in patients on intensive insulin regimens., Conclusions: The benefits and safety of dapagliflozin were maintained in high-risk patients receiving high-dose or intensive insulin regimens including SA insulin., (© 2022 by the American Diabetes Association.)
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- 2023
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17. Dapagliflozin and Prevention of Kidney Disease Among Patients With Type 2 Diabetes: Post Hoc Analyses From the DECLARE-TIMI 58 Trial.
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Mosenzon O, Raz I, Wiviott SD, Schechter M, Goodrich EL, Yanuv I, Rozenberg A, Murphy SA, Zelniker TA, Langkilde AM, Gause-Nilsson IAM, Fredriksson M, Johansson PA, Wilding JPH, McGuire DK, Bhatt DL, Leiter LA, Cahn A, Dwyer JP, Heerspink HJL, and Sabatine MS
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- Benzhydryl Compounds pharmacology, Glomerular Filtration Rate, Glucose pharmacology, Glucosides, Humans, Sodium, Diabetes Mellitus, Type 2 complications, Diabetes Mellitus, Type 2 drug therapy, Diabetic Nephropathies etiology, Myocardial Infarction complications, Sodium-Glucose Transporter 2 Inhibitors adverse effects
- Abstract
Objective: In patients with moderate to severe albuminuric kidney disease, sodium-glucose cotransporter 2 inhibitors reduce the risk of kidney disease progression. These post hoc analyses assess the effects of dapagliflozin on kidney function decline in patients with type 2 diabetes (T2D), focusing on populations with low kidney risk., Research Design and Methods: In the Dapagliflozin Effect on Cardiovascular Events-Thrombolysis in Myocardial Infarction 58 (DECLARE-TIMI 58) trial, patients with T2D at high cardiovascular risk were randomly assigned to dapagliflozin versus placebo. Outcomes were analyzed by treatment arms, overall, and by Kidney Disease: Improving Global Outcomes (KDIGO) risk categories. The prespecified kidney-specific composite outcome was a sustained decline ≥40% in the estimated glomerular filtration rate (eGFR) to <60 mL/min/1.73 m2, end-stage kidney disease, and kidney-related death. Other outcomes included incidence of categorical eGFR decline of different thresholds and chronic (6 month to 4 year) or total (baseline to 4 year) eGFR slopes., Results: Most participants were in the low-moderate KDIGO risk categories (n = 15,201 [90.3%]). The hazard for the kidney-specific composite outcome was lower with dapagliflozin across all KDIGO risk categories (P-interaction = 0.97), including those at low risk (hazard ratio [HR] 0.54, 95% CI 0.38-0.77). Risks for categorical eGFR reductions (≥57% [in those with baseline eGFR ≥60 mL/min/1.73 m2], ≥50%, ≥40%, and ≥30%) were lower with dapagliflozin (HRs 0.52, 0.57, 0.55, and 0.70, respectively; P < 0.05). Slopes of eGFR decline favored dapagliflozin across KDIGO risk categories, including the low KDIGO risk (between-arm differences of 0.87 [chronic] and 0.55 [total] mL/min/1.73 m2/year; P < 0.0001)., Conclusions: Dapagliflozin mitigated kidney function decline in patients with T2D at high cardiovascular risk, including those with low KDIGO risk, suggesting a role of dapagliflozin in the early prevention of diabetic kidney disease., (© 2022 by the American Diabetes Association.)
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- 2022
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18. The Effect of Dapagliflozin on Albuminuria in DECLARE-TIMI 58.
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Mosenzon O, Wiviott SD, Heerspink HJL, Dwyer JP, Cahn A, Goodrich EL, Rozenberg A, Schechter M, Yanuv I, Murphy SA, Zelniker TA, Gause-Nilsson IAM, Langkilde AM, Fredriksson M, Johansson PA, Bhatt DL, Leiter LA, McGuire DK, Wilding JPH, Sabatine MS, and Raz I
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- Albuminuria drug therapy, Benzhydryl Compounds therapeutic use, Glomerular Filtration Rate, Glucosides therapeutic use, Humans, Diabetes Mellitus, Type 2 complications, Diabetes Mellitus, Type 2 drug therapy, Sodium-Glucose Transporter 2 Inhibitors therapeutic use
- Abstract
Objective: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) improve albuminuria in patients with high cardiorenal risk. We report albuminuria change in the Dapagliflozin Effect on Cardiovascular Events (DECLARE-TIMI 58) cardiovascular outcome trial, which included populations with lower cardiorenal risk., Research Design and Methods: DECLARE-TIMI 58 randomized 17,160 patients with type 2 diabetes, creatinine clearance >60 mL/min, and either atherosclerotic cardiovascular disease (CVD; 40.6%) or risk-factors for CVD (59.4%) to dapagliflozin or placebo. Urinary albumin-to-creatinine ratio (UACR) was tested at baseline, 6 months, 12 months, and yearly thereafter. The change in UACR over time was measured as a continuous and categorical variable (≤15, >15 to <30, ≥30 to ≤300, and >300 mg/g) by treatment arm. The composite cardiorenal outcome was a ≥40% sustained decline in the estimated glomerular filtration rate (eGFR) to <60 mL/min/1.73 m
2 , end-stage kidney disease, and cardiovascular or renal death; specific renal outcome included all except cardiovascular death., Results: Baseline UACR was available for 16,843 (98.15%) participants: 9,067 (53.83%) with ≤15 mg/g, 2,577 (15.30%) with >15 to <30 mg/g, 4,030 (23.93%) with 30-300 mg/g, and 1,169 (6.94%) with >300 mg/g. Measured as a continuous variable, UACR improved from baseline to 4.0 years with dapagliflozin, compared with placebo, across all UACR and eGFR categories (all P < 0.0001). Sustained confirmed ≥1 category improvement in UACR was more common in dapagliflozin versus placebo (hazard ratio 1.45 [95% CI 1.35-1.56], P < 0.0001). Cardiorenal outcome was reduced with dapagliflozin for subgroups of UACR ≥30 mg/g ( P < 0.0125, Pinteraction = 0.033), and the renal-specific outcome was reduced for all UACR subgroups ( P < 0.05, Pinteraction = 0.480)., Conclusions: In DECLARE-TIMI 58, dapagliflozin demonstrated a favorable effect on UACR and renal-specific outcome across baseline UACR categories, including patients with normal albumin excretion. The results suggest a role for SGLT2i also in the primary prevention of diabetic kidney disease., (© 2021 by the American Diabetes Association.)- Published
- 2021
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19. Cardiovascular, Renal, and Metabolic Outcomes of Dapagliflozin Versus Placebo in a Primary Cardiovascular Prevention Cohort: Analyses From DECLARE-TIMI 58.
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Cahn A, Raz I, Leiter LA, Mosenzon O, Murphy SA, Goodrich EL, Yanuv I, Rozenberg A, Bhatt DL, McGuire DK, Wilding JPH, Gause-Nilsson IAM, Langkilde AM, Sabatine MS, and Wiviott SD
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- Benzhydryl Compounds therapeutic use, Glucosides adverse effects, Humans, Primary Prevention, Treatment Outcome, Cardiovascular Diseases prevention & control, Diabetes Mellitus, Type 2 drug therapy, Heart Failure
- Abstract
Objective: International guidelines propose prescribing sodium-glucose cotransporter 2 (SGLT2) inhibitors to patients with type 2 diabetes (T2D) as secondary prevention in patients with established atherosclerotic cardiovascular disease (ASCVD) or for primary prevention of cardiovascular events in high-risk patients with multiple risk factors (MRF) for ASCVD. The current analyses expand on the cardiovascular renal and metabolic effects of SGLT2 inhibitors in MRF patients., Research Design and Methods: In DECLARE-TIMI 58, 17,160 patients with T2D and MRF (59.4%) or established ASCVD (40.6%) were randomized to dapagliflozin versus placebo; patients were followed for a median of 4.2 years. The cardiovascular and renal outcomes in the MRF cohort were studied across clinically relevant subgroups for treatment effect and subgroup-based treatment interaction., Results: Among patients with MRF, the reduction with dapagliflozin in risk of cardiovascular death or hospitalization for heart failure (CVD/HHF) (hazard ratio [HR] 0.84, 95% CI 0.67-1.04) and the renal-specific outcome (HR 0.51, 95% CI 0.37-0.69) did not differ from that for patients with ASCVD ( P 0.99 and 0.72, respectively). The effect on CVD/HHF was entirely driven by a reduction in HHF (HR 0.64, 95% CI 0.46-0.88). The benefits of dapagliflozin on HHF and on the renal-specific outcome, among the subset with MRF, were directionally consistent across clinically relevant subgroups. At 48 months, HbA
interaction 0.99 and 0.72, respectively). The effect on CVD/HHF was entirely driven by a reduction in HHF (HR 0.64, 95% CI 0.46-0.88). The benefits of dapagliflozin on HHF and on the renal-specific outcome, among the subset with MRF, were directionally consistent across clinically relevant subgroups. At 48 months, HbA1c , weight, systolic blood pressure, and urinary albumin-to-creatinine ratio were lower with dapagliflozin versus placebo and estimated glomerular filtration rate was higher ( P < 0.001)., Conclusions: In patients with T2D and MRF, dapagliflozin reduced the risk of HHF and adverse renal outcomes regardless of baseline characteristics. These analyses support the benefit of dapagliflozin for important outcomes in a broad primary prevention population., (© 2021 by the American Diabetes Association.)- Published
- 2021
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20. The cost-effectiveness of dapagliflozin in treating high-risk patients with type 2 diabetes mellitus: An economic evaluation using data from the DECLARE-TIMI 58 trial.
- Author
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McEwan P, Morgan AR, Boyce R, Bergenheim K, Gause-Nilsson IAM, Bhatt DL, Leiter LA, Johansson PA, Mosenzon O, Cahn A, and Wilding JPH
- Subjects
- Benzhydryl Compounds therapeutic use, Cost-Benefit Analysis, Glucosides therapeutic use, Humans, Diabetes Mellitus, Type 2 drug therapy, Diabetes Mellitus, Type 2 epidemiology
- Abstract
Aim: To undertake a cost-effectiveness analysis of dapagliflozin in treating high-risk patients with type 2 diabetes mellitus (T2DM), using both directly observed events in the DECLARE-TIMI 58 trial and surrogate risk factors to predict endpoints not captured within the trial., Methods: An established T2DM model was adapted to integrate survival curves derived from the DECLARE-TIMI 58 trial, and extrapolated over a lifetime for all-cause mortality, hospitalization for heart failure, stroke, myocardial infarction, hospitalization for unstable angina, and end-stage kidney disease. The economic analysis considered the overall DECLARE trial population, as well as reported patient subgroups. Total and incremental costs, life-years and quality-adjusted life-years associated with dapagliflozin versus placebo were estimated from the perspective of the UK healthcare payer., Results: In the UK setting, treatment with dapagliflozin compared to placebo was estimated to be dominant, with an expected increase in quality-adjusted life-years from 10.43 to 10.48 (+0.06) and a reduction in lifetime total costs from £39 451 to £36 899 (-£2552). Across all patient subgroups, dapagliflozin was estimated to be dominant, with the greatest absolute benefit in the prior heart failure subgroup (incremental lifetime costs -£4150 and quality-adjusted life-years +0.11)., Conclusions: The results of this study demonstrate that dapagliflozin compared to placebo appears to be cost-effective, when considering evidence reported from the DECLARE-TIMI 58 trial, at established UK willingness-to-pay thresholds. The findings highlight the potential of dapagliflozin to have a meaningful impact in reducing the economic burden of T2DM and its associated complications across a broad T2DM population., (© 2020 Health Economics and Outcomes Research Ltd. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)
- Published
- 2021
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21. Dapagliflozin and Cardiac, Kidney, and Limb Outcomes in Patients With and Without Peripheral Artery Disease in DECLARE-TIMI 58.
- Author
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Bonaca MP, Wiviott SD, Zelniker TA, Mosenzon O, Bhatt DL, Leiter LA, McGuire DK, Goodrich EL, De Mendonca Furtado RH, Wilding JPH, Cahn A, Gause-Nilsson IAM, Johanson P, Fredriksson M, Johansson PA, Langkilde AM, Raz I, and Sabatine MS
- Subjects
- Aged, Female, Humans, Kidney blood supply, Male, Middle Aged, Benzhydryl Compounds administration & dosage, Diabetes Mellitus, Type 2 drug therapy, Diabetes Mellitus, Type 2 mortality, Diabetes Mellitus, Type 2 physiopathology, Extremities blood supply, Glucosides administration & dosage, Kidney Diseases mortality, Kidney Diseases physiopathology, Kidney Diseases prevention & control, Myocardial Infarction mortality, Myocardial Infarction physiopathology, Myocardial Infarction prevention & control, Peripheral Arterial Disease drug therapy, Peripheral Arterial Disease mortality, Peripheral Arterial Disease physiopathology, Stroke mortality, Stroke physiopathology, Stroke prevention & control
- Abstract
Background: Patients with peripheral artery disease (PAD) are at heightened risk of cardiovascular complications. The sodium-glucose cotransporter 2 inhibitor dapagliflozin reduces the risk for hospitalization for heart failure (HHF) and kidney events in patients with type 2 diabetes mellitus. An increased risk of amputation has been observed with canagliflozin in 1 previous trial. We examined cardiovascular and kidney efficacy and the risk of limb-related events in patients with and without PAD in an exploratory analysis., Methods: A total of 17 160 patients with type 2 diabetes mellitus, including 1025 (6%) with PAD, were randomized. Key efficacy outcomes were MACE (cardiovascular [CV] death, myocardial infarction, stroke), CV death/HHF, and progression of kidney disease. Amputations, peripheral revascularization, and limb ischemic adverse events were site-reported and categorized by a blinded reviewer., Results: Patients in the placebo arm with PAD versus those without tended to have higher adjusted risk of CV death, myocardial infarction, or stroke (adjusted hazard ratio [HR], 1.23 [95% CI, 0.97-1.56], P =0.094) and significantly higher adjusted risk of CV death/HHF (adjusted HR, 1.60 [95% CI, 1.21-2.12], P =0.0010) and progression of kidney disease (adjusted HR, 1.51 [95% CI, 1.13 - 2.03], P =0.0058), and limb adverse events (adjusted HR, 8.37, P <0.001). The relative risk reductions with dapagliflozin for CV death/HHF (HR, 0.86, PAD; HR, 0.82, no-PAD; P -interaction=0.79) and progression of kidney disease (HR, 0.78, PAD; HR, 0.76, no-PAD; P -interaction=0.84) were consistent regardless of PAD. There were 560 patients who had at least 1 limb ischemic event, 454 patients with at least 1 peripheral revascularization, and 236 patients with at least 1 amputation, with a total of 407 amputations reported. Overall, there were no significant differences in any limb outcome with dapagliflozin versus placebo including limb ischemic adverse events (HR, 1.07 [95% CI, 0.90-1.26]) and amputation (HR, 1.09 [95% CI, 0.84-1.40]), with no significant interactions by a history of PAD versus not ( P -interactions=0.30 and 0.093, respectively)., Conclusions: Patients with versus without PAD are at a higher risk of CV death of CV death, HHF, and kidney outcomes, and have a consistent benefits for CV death/HHF and progression of kidney disease with dapagliflozin. Patients with PAD had a higher risk of limb events, with no consistent pattern of incremental risk observed with dapagliflozin. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01730534.
- Published
- 2020
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22. Dapagliflozin and Cardiovascular Outcomes in Patients With Type 2 Diabetes Mellitus and Previous Myocardial Infarction.
- Author
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Furtado RHM, Bonaca MP, Raz I, Zelniker TA, Mosenzon O, Cahn A, Kuder J, Murphy SA, Bhatt DL, Leiter LA, McGuire DK, Wilding JPH, Ruff CT, Nicolau JC, Gause-Nilsson IAM, Fredriksson M, Langkilde AM, Sabatine MS, and Wiviott SD
- Subjects
- Aged, Benzhydryl Compounds adverse effects, Brain Ischemia diagnosis, Brain Ischemia mortality, Cause of Death, Diabetes Mellitus, Type 2 diagnosis, Diabetes Mellitus, Type 2 mortality, Disease Progression, Double-Blind Method, Female, Glucosides adverse effects, Heart Failure diagnosis, Heart Failure mortality, Humans, Male, Middle Aged, Myocardial Infarction diagnosis, Myocardial Infarction mortality, Recurrence, Risk Assessment, Risk Factors, Sodium-Glucose Transporter 2 Inhibitors adverse effects, Stroke diagnosis, Stroke mortality, Time Factors, Treatment Outcome, Benzhydryl Compounds therapeutic use, Brain Ischemia epidemiology, Diabetes Mellitus, Type 2 drug therapy, Glucosides therapeutic use, Heart Failure therapy, Hospitalization, Myocardial Infarction epidemiology, Sodium-Glucose Transporter 2 Inhibitors therapeutic use, Stroke epidemiology
- Abstract
Background: Sodium glucose transporter-2 inhibitors reduce the risk of major adverse cardiovascular events (MACE) in patients with type 2 diabetes mellitus and a history of atherosclerotic cardiovascular disease. Because of their baseline risk, patients with previous myocardial infarction (MI) may derive even greater benefit from sodium glucose transporter-2 inhibitor therapy., Methods: DECLARE-TIMI 58 (Dapagliflozin Effect on Cardiovascular Events-Thrombolysis in Myocardial Infarction 58) randomized 17 160 patients with type 2 diabetes mellitus and either established atherosclerotic cardiovascular disease (n=6974) or multiple risk factors (n=10 186) to dapagliflozin versus placebo. The 2 primary end points were composite of MACE (cardiovascular death, MI, or ischemic stroke) and the composite of cardiovascular death or hospitalization for heart failure. Those with previous MI (n=3584) made up a prespecified subgroup of interest., Results: In patients with previous MI (n=3584), dapagliflozin reduced the relative risk of MACE by 16% and the absolute risk by 2.6% (15.2% versus 17.8%; hazard ratio [HR], 0.84; 95% CI, 0.72-0.99; P=0.039), whereas there was no effect in patients without previous MI (7.1% versus 7.1%; HR, 1.00; 95% CI, 0.88-1.13; P=0.97; P for interaction for relative difference=0.11; P for interaction for absolute risk difference=0.048), including in patients with established atherosclerotic cardiovascular disease but no history of MI (12.6% versus 12.8%; HR, 0.98; 95% CI, 0.81-1.19). There seemed to be a greater benefit for MACE within 2 years after the last acute event ( P for interaction trend=0.007). The relative risk reductions in cardiovascular death/hospitalization for heart failure were more similar, but the absolute risk reductions tended to be greater: 1.9% (8.6% versus 10.5%; HR, 0.81; 95% CI, 0.65-1.00; P=0.046) and 0.6% (3.9% versus 4.5%; HR, 0.85; 95% CI, 0.72-1.00; P=0.055) in patients with and without previous MI, respectively ( P interaction for relative difference=0.69; P interaction for absolute risk difference=0.010)., Conclusions: Patients with type 2 diabetes mellitus and previous MI are at high risk of MACE and cardiovascular death/hospitalization for heart failure. Dapagliflozin appears to robustly reduce the risk of both composite outcomes in these patients. Future studies should aim to confirm the large clinical benefits with sodium glucose transporter-2 inhibitors we observed in patients with previous MI., Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01730534.
- Published
- 2019
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23. Dapagliflozin and Cardiovascular Outcomes in Type 2 Diabetes.
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Wiviott SD, Raz I, Bonaca MP, Mosenzon O, Kato ET, Cahn A, Silverman MG, Zelniker TA, Kuder JF, Murphy SA, Bhatt DL, Leiter LA, McGuire DK, Wilding JPH, Ruff CT, Gause-Nilsson IAM, Fredriksson M, Johansson PA, Langkilde AM, and Sabatine MS
- Subjects
- Aged, Benzhydryl Compounds adverse effects, Cardiovascular Diseases etiology, Cardiovascular Diseases mortality, Diabetes Mellitus, Type 2 complications, Female, Glucosides adverse effects, Heart Failure epidemiology, Hospitalization statistics & numerical data, Humans, Male, Middle Aged, Sodium-Glucose Transporter 2 Inhibitors adverse effects, Benzhydryl Compounds therapeutic use, Cardiovascular Diseases prevention & control, Diabetes Mellitus, Type 2 drug therapy, Glucosides therapeutic use, Sodium-Glucose Transporter 2 Inhibitors therapeutic use
- Abstract
Background: The cardiovascular safety profile of dapagliflozin, a selective inhibitor of sodium-glucose cotransporter 2 that promotes glucosuria in patients with type 2 diabetes, is undefined., Methods: We randomly assigned patients with type 2 diabetes who had or were at risk for atherosclerotic cardiovascular disease to receive either dapagliflozin or placebo. The primary safety outcome was a composite of major adverse cardiovascular events (MACE), defined as cardiovascular death, myocardial infarction, or ischemic stroke. The primary efficacy outcomes were MACE and a composite of cardiovascular death or hospitalization for heart failure. Secondary efficacy outcomes were a renal composite (≥40% decrease in estimated glomerular filtration rate to <60 ml per minute per 1.73 m
2 of body-surface area, new end-stage renal disease, or death from renal or cardiovascular causes) and death from any cause., Results: We evaluated 17,160 patients, including 10,186 without atherosclerotic cardiovascular disease, who were followed for a median of 4.2 years. In the primary safety outcome analysis, dapagliflozin met the prespecified criterion for noninferiority to placebo with respect to MACE (upper boundary of the 95% confidence interval [CI], <1.3; P<0.001 for noninferiority). In the two primary efficacy analyses, dapagliflozin did not result in a lower rate of MACE (8.8% in the dapagliflozin group and 9.4% in the placebo group; hazard ratio, 0.93; 95% CI, 0.84 to 1.03; P=0.17) but did result in a lower rate of cardiovascular death or hospitalization for heart failure (4.9% vs. 5.8%; hazard ratio, 0.83; 95% CI, 0.73 to 0.95; P=0.005), which reflected a lower rate of hospitalization for heart failure (hazard ratio, 0.73; 95% CI, 0.61 to 0.88); there was no between-group difference in cardiovascular death (hazard ratio, 0.98; 95% CI, 0.82 to 1.17). A renal event occurred in 4.3% in the dapagliflozin group and in 5.6% in the placebo group (hazard ratio, 0.76; 95% CI, 0.67 to 0.87), and death from any cause occurred in 6.2% and 6.6%, respectively (hazard ratio, 0.93; 95% CI, 0.82 to 1.04). Diabetic ketoacidosis was more common with dapagliflozin than with placebo (0.3% vs. 0.1%, P=0.02), as was the rate of genital infections that led to discontinuation of the regimen or that were considered to be serious adverse events (0.9% vs. 0.1%, P<0.001)., Conclusions: In patients with type 2 diabetes who had or were at risk for atherosclerotic cardiovascular disease, treatment with dapagliflozin did not result in a higher or lower rate of MACE than placebo but did result in a lower rate of cardiovascular death or hospitalization for heart failure, a finding that reflects a lower rate of hospitalization for heart failure. (Funded by AstraZeneca; DECLARE-TIMI 58 ClinicalTrials.gov number, NCT01730534 .).- Published
- 2019
- Full Text
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