194SGLT-2 inhibitors versus GLP-1 receptor agonists and risk of mortality, chronic kidney disease and hospitalisation for heart failure in patients with type 2 diabetes

Abstract Background Two promising classes of second-line glucose-lowering drugs, the sodium-glucose cotransporter-2 inhibitors (SGLT-2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA), have both been shown to lower the risk of cardiovascular (CV) outcomes in patients with type 2 diabetes, however no head-to-head comparisons exist. Purpose The aim of this study was to examine the risk of CV and all-cause mortality, incident chronic kidney disease (CKD) and hospitalisation for heart failure (HF) in association with SGLT-2i versus GLP-1RA use. Methods New users of SGLT-2i and GLP-1RA, with no prior use of drugs from the comparison class, were identified between 2012–2016, using individual-level linkage of Danish nationwide registries. The absolute risk of CV was calculated using the Aalen-Johansen Estimator with non-CV mortality as competing risk. The hazard ratios (HR) of CV and all-cause mortality, incident CKD and hospitalisation for HF were estimated using Cox regression and adjusted for age, sex, diabetes duration and other outcome specific risk factors. Results The study included a total of 8,304 SGLT-2i users (median age: 63 years [interquartile range (IQR): 54–70], males: 63%, dapagliflozin: 60.5%, empagliflozin: 36.5%) and 13,318 GLP-1RA users (median age: 60 years [IQR: 50–68], males: 54%, liraglutide: 97.4%) with a median follow-up time of 2.0 [(IQR): 1.5–2.9] years and 3.6 [IQR: 2.1–5.0] years, respectively. At baseline 29% of SGLT-2i and 30% of GLP-1RA users had CV disease. The absolute risks are shown in Figure 1. Compared with GLP-1RA, initiation of SGLT-2i was in adjusted analyses associated with a lower risk of CV mortality (HR: 0.49 [confidence interval (CI): 0.37–0.65]), all-cause mortality [HR: 0.79 [CI: 0.68–0.93], incident CKD (HR: 0.42 [CI: 0.34–0.53] and hospitalisation for HF (HR: 0.68 [CI: 0.59–0.78]). Figure 1 Conclusion SGLT-2i use was associated with a significantly lower risk of CV and all-cause mortality, incident CKD and hospitalisation for HF in comparison with GLP-1RA use. Acknowledgement/Funding The Danish Heart Foundation (18-R125-A8381-22082)

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Finerenone Reduces Risk of Incident Heart Failure in Patients With Chronic Kidney Disease and Type 2 Diabetes: Analyses from the FIGARO-DKD Trial

Circulation ◽

10.1161/circulationaha.121.057983 ◽

2021 ◽

Author(s):

Gerasimos Filippatos ◽

Stefan D. Anker ◽

Rajiv Agarwal ◽

Luis M. Ruilope ◽

Peter Rossing ◽

...

Keyword(s):

Heart Failure ◽

Type 2 Diabetes ◽

Chronic Kidney Disease ◽

Kidney Disease ◽

Lower Risk ◽

Cardiovascular Death ◽

History Of ◽

The Impact ◽

New Onset

Background: Chronic kidney disease (CKD) and type 2 diabetes (T2D) are independently associated with heart failure (HF), a leading cause of morbidity and mortality. In the FIDELIO-DKD and FIGARO DKD trials, finerenone (a selective, nonsteroidal mineralocorticoid receptor antagonist) improved cardiovascular outcomes in patients with albuminuric CKD and T2D. These prespecified analyses from FIGARO-DKD assessed the impact of finerenone on clinically important HF outcomes. Methods: Patients with T2D and albuminuric CKD (urine albumin-to-creatinine ratio [UACR] ≥30 to <300 mg/g and estimated glomerular filtration rate [eGFR] ≥25 to ≤90 ml/min/1.73 m 2 , or UACR ≥300 to ≤5000 mg/g and eGFR ≥60 ml/min/1.73 m 2 ,), without symptomatic HF with reduced ejection fraction, were randomized to finerenone or placebo. Time-to-first event outcomes included: new-onset HF (first hospitalization for HF [HHF] in patients without a history of HF at baseline); cardiovascular death or first HHF; HF-related death or first HHF; first HHF; cardiovascular death or total (first or recurrent) HHF; HF-related death or total HHF; and total HHF. Outcomes were evaluated in the overall population and in prespecified subgroups categorized by baseline HF history (as reported by the investigators). Results: Overall, 7352 patients were included in these analyses; 571 (7.8%) had a history of HF at baseline. New-onset HF was significantly reduced with finerenone versus placebo (1.9% versus 2.8%; hazard ratio [HR], 0.68 [95% CI 0.50-0.93]; P =0.0162). In the overall population, the incidences of all HF outcomes analyzed were significantly lower with finerenone than placebo, including a 18% lower risk of cardiovascular death or first HHF (HR, 0.82 [95% CI 0.70-0.95]; P =0.011), a 29% lower risk of first HHF (HR, 0.71 [95% CI 0.56-0.90]; P =0.0043) and a 30% lower rate of total HHF (rate ratio, 0.70 [95% CI, 0.52- 0.94]). The effects of finerenone on improving HF outcomes were not modified by a history of HF. The incidence of treatment-emergent adverse events was balanced between treatment groups. Conclusions: The results from these FIGARO-DKD analyses demonstrate that finerenone reduces new-onset HF and improves other HF outcomes in patients with CKD and T2D, irrespective of a history of HF.

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Glycaemic Control in Diabetes

10.1007/164_2021_537 ◽

2021 ◽

Author(s):

D. Müller-Wieland ◽

J. Brandts ◽

M. Verket ◽

N. Marx ◽

K. Schütt

Keyword(s):

Heart Failure ◽

Type 2 Diabetes ◽

Chronic Kidney Disease ◽

Blood Glucose ◽

Kidney Disease ◽

Treatment Guidelines ◽

Glucose Lowering ◽

Receptor Agonists ◽

Cardiovascular Endpoint

AbstractReduction of glucose is the hallmark of diabetes therapy proven to reduce micro- and macro-vascular risk in patients with type 1 diabetes. However glucose-lowering efficacy trials in type 2 diabetes didn’t show major cardiovascular benefit. Then, a paradigm change in the treatment of patients with type 2 diabetes has emerged due to the introduction of new blood glucose-lowering agents. Cardiovascular endpoint studies have proven HbA1c-independent cardioprotective effects for GLP-1 receptor agonists and SGLT-2 inhibitors. Furthermore, SGLT-2 inhibitors reduce the risk for heart failure and chronic kidney disease. Mechanisms for these blood glucose independent drug target-related effects are still an enigma. Recent research has shown that GLP-1 receptor agonists might have anti-inflammatory and plaque stabilising effects whereas SGLT-2 inhibitors primarily reduce pre- and after-load of the heart and increase work load efficiency of the heart. In addition, reduction of intraglomerular pressure, improved energy supply chains and water regulation appear to be major mechanisms for renoprotection by SGLT-2 inhibitors. These studies and observations have led to recent changes in clinical recommendations and treatment guidelines for type 2 diabetes. In patients with high or very high cardio-renal risk, SGLT-2 inhibitors or GLP-1 receptor agonists have a preferred recommendation independent of baseline HbA1c levels due to cardioprotection. In patients with chronic heart failure, chronic kidney disease or at respective risks SGLT-2 inhibitors are the preferred choice. Therefore, the treatment paradigm of glucose control in diabetes has changed towards using diabetes drugs with evidence-based organ protection improving clinical prognosis.

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Cardiovascular and mortality benefits of sodium–glucose co-transporter-2 inhibitors in patients with type 2 diabetes mellitus: CVD-Real Catalonia

Cardiovascular Diabetology ◽

10.1186/s12933-021-01323-5 ◽

2021 ◽

Vol 20 (1) ◽

Author(s):

Jordi Real ◽

Bogdan Vlacho ◽

Emilio Ortega ◽

Joan Antoni Vallés ◽

Manel Mata-Cases ◽

...

Keyword(s):

Heart Failure ◽

Type 2 Diabetes ◽

Chronic Kidney Disease ◽

Kidney Disease ◽

Propensity Score ◽

Lower Risk ◽

Previous History ◽

Incidence Rates ◽

Real World Data

Abstract Background Evidence from prospective cardiovascular (CV) outcome trials in type 2 diabetes (T2DM) patients supports the use of sodium–glucose co-transporter-2 inhibitors (SGLT2i) to reduce the risk of CV events. In this study, we compared the risk of several CV outcomes between new users of SGLT2i and other glucose-lowering drugs (oGLDs) in Catalonia, Spain. Methods CVD-REAL Catalonia was a retrospective cohort study using real-world data routinely collected between 2013 and 2016. The cohorts of new users of SGLT2i and oGLDs were matched by propensity score on a 1:1 ratio. We compared the incidence rates and hazard ratio (HR) for all-cause death, hospitalization for heart failure, chronic kidney disease, and modified major adverse CV event (MACE; all-cause mortality, myocardial infarction, or stroke). Results After propensity score matching, 12,917 new users were included in each group. About 27% of users had a previous history of CV disease. In the SGLT2i group, the exposure time was 60% for dapagliflozin, 26% for empagliflozin and 14% for canagliflozin. The use of SGLT2i was associated with a lower risk of heart failure (HR: 0.59; 95% confidence interval [CI] 0.47–0.74; p < 0.001), all-cause death (HR = 0.41; 95% CI 0.31–0.54; p < 0.001), all-cause death or heart failure (HR = 0.55; 95% CI 0.47–0.63; p < 0.001), modified MACE (HR = 0.62; 95% CI 0.52–0.74; p < 0.001), and chronic kidney disease (HR = 0.66; 95% CI 0.54–0.80; p < 0.001). Conclusions In this large, retrospective observational study of patients with T2DM from a Catalonia, initiation of SGLT-2i was associated with lower risk of mortality, as well as heart failure and CKD.

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Metformin Use and Clinical Outcomes Among Patients With Diabetes Mellitus With or Without Heart Failure or Kidney Dysfunction

Circulation ◽

10.1161/circulationaha.119.040144 ◽

2019 ◽

Vol 140 (12) ◽

pp. 1004-1014 ◽

Cited By ~ 17

Author(s):

Brian A. Bergmark ◽

Deepak L. Bhatt ◽

Darren K. McGuire ◽

Avivit Cahn ◽

Ofri Mosenzon ◽

...

Keyword(s):

Diabetes Mellitus ◽

Heart Failure ◽

Type 2 Diabetes ◽

Chronic Kidney Disease ◽

Type 2 Diabetes Mellitus ◽

Kidney Disease ◽

Cardiovascular Death ◽

Inverse Probability ◽

All Cause Mortality

Background: Metformin is first-line therapy for type 2 diabetes mellitus, although its effects on the cardiovascular system are unproved. Methods: In this post hoc analysis, patients in SAVOR-TIMI 53 (Saxagliptin and Cardiovascular Outcomes in Patients With Type 2 Diabetes Mellitus) with baseline biomarker samples (n=12 156) were classified as ever versus never taking metformin during the trial period. Associations between metformin exposure and outcomes were estimated with inverse probability of treatment weighting Cox modeling for the composite end point of cardiovascular death, myocardial infarction, or ischemic stroke, as well as cardiovascular death and all-cause mortality, with biomarkers included as covariates. Additional sensitivity analyses included propensity score matching and Cox multivariable models. Results: Of the 12 156 patients with baseline biomarker samples, 8971 (74%) had metformin exposure, 1611 (13%) had prior heart failure, and 1332 (11%) had at least moderate chronic kidney disease (estimated glomerular filtration rate ≤45 mL·min −1 ·1.73 m −2 ). Metformin use was associated with no difference in risk for the composite end point (hazard ratio for inverse probability of treatment weighting, 0.92 [95% CI, 0.76–1.11]) but lower risk of all-cause mortality (hazard ratio for inverse probability of treatment weighting, 0.75 [95% CI, 0.59–0.95]). There was no significant relationship between metformin use and these end points in patients with prior heart failure or moderate to severe chronic kidney disease. Conclusions: In a cohort of 12 156 patients with type 2 diabetes mellitus and high cardiovascular risk, metformin use was associated with lower rates of all-cause mortality, including after adjustment for clinical variables and biomarkers, but not lower rates of the composite end point of cardiovascular death, myocardial infarction, or ischemic stroke. This association was most apparent in patients without prior heart failure or moderate to severe chronic kidney disease. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01107886.

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