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  • 1
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    Saxagliptin and Cardiovascular Outcomes in Patients With Type 2 Diabetes and Moderate or Severe Renal Impairment: Observations From the SAVOR-TIMI 53 Trial
    American Diabetes Association ; 2015
    In:  Diabetes Care Vol. 38, No. 4 ( 2015-04-01), p. 696-705
    Details
    In: Diabetes Care, American Diabetes Association, Vol. 38, No. 4 ( 2015-04-01), p. 696-705
    Abstract: The glycemic management of patients with type 2 diabetes mellitus (T2DM) and renal impairment is challenging, with few treatment options. We investigated the effect of saxagliptin in the Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus (SAVOR)-Thrombolysis in Myocardial Infarction (TIMI) 53 trial according to baseline renal function. RESEARCH DESIGN AND METHODS Patients with T2DM at risk for cardiovascular events were stratified as having normal or mildly impaired renal function (estimated glomerular filtration rate [eGFR] & gt;50 mL/min/1.73 m2; n = 13,916), moderate renal impairment (eGFR 30–50 mL/min/1.73 m2; n = 2,240), or severe renal impairment (eGFR & lt;30 mL/min/1.73 m2; n = 336) and randomized to receive saxagliptin or placebo. The primary end point was cardiovascular death, myocardial infarction, or ischemic stroke. RESULTS After a median duration of 2 years, saxagliptin neither increased nor decreased the risk of the primary and secondary composite end points compared with placebo, irrespective of renal function (all P for interactions ≥0.19). Overall, the risk of hospitalization for heart failure among the three eGFR groups of patients was 2.2% (referent), 7.4% (adjusted hazard ratio [HR] 2.38 [95% CI 1.95–2.91] , P & lt; 0.001), and 13.0% (adjusted HR 4.59 [95% CI 3.28–6.28], P & lt; 0.001), respectively. The relative risk of hospitalization for heart failure with saxagliptin was similar (P for interaction = 0.43) in patients with eGFR & gt;50 mL/min/1.73 m2 (HR 1.23 [95% CI 0.99–1.55]), eGFR 30–50 mL/min/1.73 m2 (HR 1.46 [95% CI 1.07–2.00] ), and in patients with eGFR & lt;30 (HR 0.94 [95% CI 0.52–1.71]). Patients with renal impairment achieved reductions in microalbuminuria with saxagliptin (P = 0.041) that were similar to those of the overall trial population. CONCLUSIONS Saxagliptin did not affect the risk of ischemic cardiovascular events, increased the risk of heart failure hospitalization, and reduced progressive albuminuria, irrespective of baseline renal function.
    Type of Medium: Online Resource
    ISSN: 0149-5992 , 1935-5548
    URL: Article
    DOI: 10.2337/dc14-1850
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2015
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  • 2
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    Relationship between baseline cardiac biomarkers and cardiovascular death or hospitalization for heart failure with and without sodium–glucose co‐transporter 2 inhibitor therapy in DECLARE‐TIMI 58
    Wiley ; 2021
    In:  European Journal of Heart Failure Vol. 23, No. 6 ( 2021-06), p. 1026-1036
    Details
    In: European Journal of Heart Failure, Wiley, Vol. 23, No. 6 ( 2021-06), p. 1026-1036
    Abstract: Dapagliflozin reduced the risk of the composite of cardiovascular (CV) death or hospitalization for heart failure (HHF) in patients with type 2 diabetes mellitus in DECLARE‐TIMI 58. We hypothesized that baseline N‐terminal pro B‐type natriuretic peptide (NT‐proBNP) and high‐sensitivity troponin T (hsTnT) levels would help identify patients who are at higher baseline risk and we describe the treatment effects of dapagliflozin in patients according to their baseline NT‐proBNP and hsTnT levels. Methods and results This was a pre‐specified biomarker study from DECLARE‐TIMI 58, a randomized, double‐blind, placebo‐controlled CV outcomes trial of dapagliflozin. Baseline NT‐proBNP and hsTnT levels were measured in the TIMI Clinical Trials Laboratory in 14 565 patients. Among the included patients, 9143 patients (62.8%) were male, 1464 (10.1%) had a history of heart failure and the mean age was 63.9 years. The median baseline NT‐proBNP and hsTnT levels were 75 pg/mL [interquartile range (IQR) 35–165] and 10.2 pg/mL (IQR 6.9–15.5), respectively. Patients with higher NT‐proBNP and hsTnT quartiles had higher rates of CV death/HHF (Q4 vs. Q1: NT‐proBNP: 4‐year Kaplan–Meier event rates 13.7% vs. 1.0%; hsTnT: 11.8% vs. 1.4%; P ‐trend 〈 0.001). Dapagliflozin consistently reduced the relative risk of CV death/HHF regardless of baseline NT‐proBNP ( P ‐interaction 0.72) or hsTnT quartiles ( P ‐interaction 0.93). Given their higher baseline risk, patients with NT‐proBNP and/or hsTnT levels above the median derived larger absolute risk reductions with dapagliflozin (NT‐proBNP 1.9% vs. 0%, P ‐interaction 0.010; hsTnT 1.8% vs. 0.1%, P ‐interaction 0.026). Conclusion Patients with type 2 diabetes mellitus and higher NT‐proBNP or hsTnT levels are at increased risk of CV death and HHF. Dapagliflozin reduced the relative risk of CV death/HHF irrespective of NT‐proBNP and hsTnT levels, with greater absolute risk reductions seen in patients with higher baseline biomarker levels.
    Type of Medium: Online Resource
    ISSN: 1388-9842 , 1879-0844
    URL: Issue
    URL: Article
    DOI: 10.1002/ejhf.v23.6
    DOI: 10.1002/ejhf.2073
    Language: English
    Publisher: Wiley
    Publication Date: 2021
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  • 3
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    The Effect of Dapagliflozin on Albuminuria in DECLARE-TIMI 58
    American Diabetes Association ; 2021
    In:  Diabetes Care Vol. 44, No. 8 ( 2021-08-01), p. 1805-1815
    Details
    In: Diabetes Care, American Diabetes Association, Vol. 44, No. 8 ( 2021-08-01), p. 1805-1815
    Abstract: 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 & gt;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, & gt;15 to & lt;30, ≥30 to ≤300, and & gt;300 mg/g) by treatment arm. The composite cardiorenal outcome was a ≥40% sustained decline in the estimated glomerular filtration rate (eGFR) to & lt;60 mL/min/1.73 m2, 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 & gt;15 to & lt;30 mg/g, 4,030 (23.93%) with 30–300 mg/g, and 1,169 (6.94%) with & gt;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 & lt; 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 & lt; 0.0001). Cardiorenal outcome was reduced with dapagliflozin for subgroups of UACR ≥30 mg/g (P & lt; 0.0125, Pinteraction = 0.033), and the renal-specific outcome was reduced for all UACR subgroups (P & lt; 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.
    Type of Medium: Online Resource
    ISSN: 0149-5992 , 1935-5548
    URL: Article
    DOI: 10.2337/dc21-0076
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2021
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  • 4
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    Safety of dapagliflozin in a broad population of patients with type 2 diabetes: Analyses from the DECLARE‐TIMI 58 study
    Wiley ; 2020
    In:  Diabetes, Obesity and Metabolism Vol. 22, No. 8 ( 2020-08), p. 1357-1368
    Details
    In: Diabetes, Obesity and Metabolism, Wiley, Vol. 22, No. 8 ( 2020-08), p. 1357-1368
    Abstract: To evaluate comprehensively the safety of dapagliflozin in patients with type 2 diabetes (T2DM), with emphasis placed on potential safety concerns related to the sodium‐glucose co‐transporter‐2 inhibitor class. Methods In the Dapagliflozin Effect on Cardiovascular Events – Thrombolysis in Myocardial Infarction 58 (DECLARE‐TIMI 58) study, 17 160 patients with T2DM were randomized to dapagliflozin or placebo and followed for a median of 4.2 years. Safety was evaluated in 17 143 patients receiving at least one dose of study drug. Results Acute kidney injury occurred less frequently with dapagliflozin, and adverse events suggestive of volume depletion were balanced between treatment groups, both irrespective of baseline estimated glomerular filtration rate, blood pressure, diuretic or loop diuretic use (interaction P values 〉 0.05). Fractures and malignancies were balanced between the groups, irrespective of sex, diabetes duration or smoking (interaction P values 〉 0.05) and fewer cases of bladder cancer occurred in the dapagliflozin versus the placebo group. Diabetic ketoacidosis was very rare, but more frequent with dapagliflozin versus placebo (27 vs. 12 patients with events; P = 0.02), yet signs, symptoms and contributing factors were similar in the two groups. Major hypoglycaemia occurred less frequently with dapagliflozin versus placebo, regardless of baseline use of either insulin or sulphonylureas (interaction P values 〉 0.05). There were more adverse events of genital infections leading to discontinuation of study drug in the dapagliflozin versus the placebo group, but serious genital infections were few and balanced between treatment groups. Urinary tract infections, acute pyelonephritis and urosepsis were also balanced between treatment groups. Conclusions Dapagliflozin was well tolerated. The long duration and large number of patient‐years in DECLARE‐TIMI 58 comprehensively addressed previous safety questions, confirming the robust safety profile of dapagliflozin.
    Type of Medium: Online Resource
    ISSN: 1462-8902 , 1463-1326
    URL: Issue
    URL: Article
    DOI: 10.1111/dom.v22.8
    DOI: 10.1111/dom.14041
    Language: English
    Publisher: Wiley
    Publication Date: 2020
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  • 5
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    Dapagliflozin and Prevention of Kidney Disease Among Patients With Type 2 Diabetes: Post Hoc Analyses From the DECLARE-TIMI 58 Trial
    American Diabetes Association ; 2022
    In:  Diabetes Care Vol. 45, No. 10 ( 2022-10-01), p. 2350-2359
    Details
    In: Diabetes Care, American Diabetes Association, Vol. 45, No. 10 ( 2022-10-01), p. 2350-2359
    Abstract: 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 & lt;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 & lt; 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 & lt; 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.
    Type of Medium: Online Resource
    ISSN: 0149-5992 , 1935-5548
    URL: Article
    DOI: 10.2337/dc22-0382
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2022
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  • 6
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    Dapagliflozin and Cardiovascular Outcomes in Type 2 Diabetes
    Massachusetts Medical Society ; 2019
    In:  New England Journal of Medicine Vol. 380, No. 4 ( 2019-01-24), p. 347-357
    Details
    In: New England Journal of Medicine, Massachusetts Medical Society, Vol. 380, No. 4 ( 2019-01-24), p. 347-357
    Type of Medium: Online Resource
    ISSN: 0028-4793 , 1533-4406
    URL: Article
    DOI: 10.1056/NEJMoa1812389
    RVK:
    XA 10000
    Language: English
    Publisher: Massachusetts Medical Society
    Publication Date: 2019
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  • 7
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    Effect of Dapagliflozin on Heart Failure and Mortality in Type 2 Diabetes Mellitus
    Ovid Technologies (Wolters Kluwer Health) ; 2019
    In:  Circulation Vol. 139, No. 22 ( 2019-05-28), p. 2528-2536
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 139, No. 22 ( 2019-05-28), p. 2528-2536
    Abstract: In DECLARE-TIMI 58 (Dapagliflozin Effect on Cardiovascular Events–Thrombolysis in Myocardial Infarction 58), the sodium-glucose cotransporter 2 inhibitor dapagliflozin reduced the composite end point of cardiovascular death/hospitalization for heart failure (HHF) in a broad population of patients with type 2 diabetes mellitus. However, the impact of baseline left ventricular ejection fraction (EF) on the clinical benefit of sodium-glucose cotransporter 2 inhibition is unknown. Methods: In the DECLARE-TIMI 58 trial, baseline heart failure (HF) status was collected from all patients, and EF was collected when available. HF with reduced EF (HFrEF) was defined as EF 〈 45%. Outcomes of interest were the composite of cardiovascular death/HHF, its components, and all-cause mortality. Results: Of 17 160 patients, 671 (3.9%) had HFrEF, 1316 (7.7%) had HF without known reduced EF, and 15 173 (88.4%) had no history of HF at baseline. Dapagliflozin reduced cardiovascular death/HHF more in patients with HFrEF (hazard ratio [HR], 0.62 [95% CI, 0.45–0.86] ) than in those without HFrEF (HR, 0.88 [95% CI, 0.76–1.02]; P for interaction=0.046), in whom the treatment effect of dapagliflozin was similar in those with HF without known reduced EF (HR, 0.88 [95% CI, 0.66–1.17]) and those without HF (HR, 0.88 [95% CI, 0.74–1.03] ). Whereas dapagliflozin reduced HHF both in those with (HR, 0.64 [95% CI, 0.43–0.95]) and in those without HFrEF (HR, 0.76 [95% CI, 0.62–0.92] ), it reduced cardiovascular death only in patients with HFrEF (HR, 0.55 [95% CI, 0.34–0.90]) but not in those without HFrEF (HR, 1.08 [95% CI, 0.89–1.31] ; P for interaction=0.012). Likewise, dapagliflozin reduced all-cause mortality in patients with HFrEF (HR, 0.59 [95% CI, 0.40–0.88;) but not in those without HFrEF (HR, 0.97 [95% CI, 0.86–1.10]; P for interaction=0.016). Conclusions: In the first sodium-glucose cotransporter 2 inhibitor cardiovascular outcome trial to evaluate patients with type 2 diabetes mellitus stratified by EF, we found that dapagliflozin reduced HHF in patients with and without HFrEF and reduced cardiovascular death and all-cause mortality in patients with HFrEF. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01730534.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/CIRCULATIONAHA.119.040130
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2019
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  • 8
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    Dapagliflozin and Cardiovascular Outcomes in Patients With Type 2 Diabetes Mellitus and Previous Myocardial Infarction : Subanalysis From the DECLARE-TIMI 58 Trial
    Ovid Technologies (Wolters Kluwer Health) ; 2019
    In:  Circulation Vol. 139, No. 22 ( 2019-05-28), p. 2516-2527
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 139, No. 22 ( 2019-05-28), p. 2516-2527
    Abstract: 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.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/CIRCULATIONAHA.119.039996
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2019
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  • 9
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    Effect of Dapagliflozin on Atrial Fibrillation in Patients With Type 2 Diabetes Mellitus : Insights From the DECLARE-TIMI 58 Trial
    Ovid Technologies (Wolters Kluwer Health) ; 2020
    In:  Circulation Vol. 141, No. 15 ( 2020-04-14), p. 1227-1234
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 141, No. 15 ( 2020-04-14), p. 1227-1234
    Abstract: Atrial fibrillation (AF) and atrial flutter (AFL) are associated with both diabetes mellitus and its related comorbidities, including hypertension, obesity, and heart failure (HF). SGLT2 (sodium-glucose cotransporter 2) inhibitors have been shown to lower blood pressure, reduce weight, have salutary effects on left ventricular remodeling, and reduce hospitalization for HF and cardiovascular death in patients with type 2 diabetes mellitus. We therefore investigated whether SGLT2 inhibitors could also reduce the risk of AF/AFL. Methods: DECLARE-TIMI 58 (Dapagliflozin Effect on Cardiovascular Events–Thrombolysis in Myocardial Infarction 58) studied the efficacy and safety of the SGLT2 inhibitor dapagliflozin versus placebo in 17 160 patients with type 2 diabetes mellitus and either multiple risk factors for atherosclerotic cardiovascular disease (n=10 186) or known atherosclerotic cardiovascular disease (n=6974). We explored the effect of dapagliflozin on the first and total number of AF/AFL events in patients with (n=1116) and without prevalent AF/AFL using Cox and negative binomial models, respectively. AF/AFL events were identified by search of the safety database using MedDRA preferred terms (“atrial fibrillation,” “atrial flutter”). Results: Dapagliflozin reduced the risk of AF/AFL events by 19% (264 versus 325 events; 7.8 versus 9.6 events per 1000 patient-years; hazard ratio [HR], 0.81 [95% CI, 0.68–0.95] ; P =0.009). The reduction in AF/AFL events was consistent regardless of presence or absence of a history of AF/AFL at baseline (previous AF/AFL: HR, 0.79 [95% CI, 0.58–1.09]; no AF/AFL: HR, 0.81 [95% CI, 0.67–0.98] ; P for interaction 0.89). Similarly, presence of atherosclerotic cardiovascular disease (HR, 0.83 [95% CI, 0.66–1.04]) versus multiple risk factors (HR, 0.78 [95% CI, 0.62–0.99] ; P for interaction 0.72) or a history of HF (HF: HR, 0.78 [95% CI, 0.55–1.11]; No HF: HR, 0.81 [95% CI, 0.68–0.97] ; P for interaction 0.88) did not modify the reduction in AF/AFL events observed with dapagliflozin. Moreover, there was no effect modification by sex, history of ischemic stroke, glycated hemoglobin A 1c , body mass index, blood pressure, or estimated glomerular filtration rate (all P for interaction 〉 0.20). Dapagliflozin also reduced the total number (first and recurrent) of AF/AFL events (337 versus 432; incidence rate ratio, 0.77 [95% CI, 0.64–0.92]; P =0.005). Conclusions: Dapagliflozin decreased the incidence of reported episodes of AF/AFL adverse events in high-risk patients with type 2 diabetes mellitus. This effect was consistent regardless of the patient’s previous history of AF, atherosclerotic cardiovascular disease, or HF. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01730534.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/CIRCULATIONAHA.119.044183
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2020
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    Efficacy and Safety of Dapagliflozin in the Elderly: Analysis From the DECLARE–TIMI 58 Study
    American Diabetes Association ; 2020
    In:  Diabetes Care Vol. 43, No. 2 ( 2020-02-01), p. 468-475
    Details
    In: Diabetes Care, American Diabetes Association, Vol. 43, No. 2 ( 2020-02-01), p. 468-475
    Abstract: 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 & lt;65 years of age, 6,811 ≥65 to & lt;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 & lt;65, ≥65 to & lt;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 & lt;65, ≥65 to & lt;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 & lt;65, ≥65 to & lt;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.
    Type of Medium: Online Resource
    ISSN: 0149-5992 , 1935-5548
    URL: Article
    DOI: 10.2337/dc19-1476
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2020
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