Insulin degludec allows for better glycaemic control with a lower risk of hypoglycaemia in patients with chronic kidney disease and type 2 diabetes

2020 ◽  
Vol 162 ◽  
pp. 108094
Author(s):  
María Dolores García de Lucas ◽  
Beatriz Avilés Bueno ◽  
Francisco Rivas Ruiz ◽  
Julián Olalla Sierra
Keyword(s):  
Type 2 Diabetes ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Glycaemic Control ◽  
Lower Risk ◽  
Insulin Degludec

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

Circulation ◽  
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.

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

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.

Evidence-based use of newer agents in type 2 diabetes

2021 ◽  
Vol 3 (6) ◽  
pp. 224-234
Author(s):  
David Morris
Keyword(s):  
Heart Failure ◽  
Type 2 Diabetes ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Glycaemic Control ◽  
Side Effect ◽  
Atherosclerotic Cardiovascular Disease ◽  
Disease Case ◽  
The Impact

The DPP-4 inhibitors, GLP-1 receptor agonists and SGLT-2 inhibitors are newer agents for glycaemic control in type 2 diabetes that can offer additional health benefits. All three treatments carry a low risk of hypoglycaemia. GLP-1 RAs and SGLT-2 inhibitors are associated with weight loss and DPP-4 inhibitors are weight neutral. The GLP-1 RAs and SGLT-2 inhibitors offer protection against cardiovascular events. SGLT-2 inhibitors are the agents of choice to add on to metformin for glycaemic control in chronic kidney disease and heart failure, with GLP-1 RAs an alternative to be considered if SGLT-2 inhibitors are poorly tolerated or contraindicated. DPP-4 inhibitors are very well tolerated. Gastrointestinal side-effects can be problematic with GLP-1 RAs though frequently these settle with time. Genital thrush is a common side-effect with SGLT-2 inhibitors and diabetic ketoacidosis is a rare but serious side-effect. It is important that healthcare professionals with responsibility in diabetes familiarise themselves with these treatments in order to know when and how to safely and effectively deploy them. The selection of newer agents should be based on careful assessment of individual circumstances. Overall, the standpoint has shifted from a largely glucocentric approach to one considering the impact of treatments on weight, risk of hypoglycaemia, and co-morbidities (notably atherosclerotic cardiovascular disease, heart failure and chronic kidney disease). Case histories are used in the article to illustrate the pragmatic use of these agents.

FC 063DAPAGLIFLOZIN DECREASES ALBUMINURIA IN PATIENTS WITH CHRONIC KIDNEY DISEASE WITH AND WITHOUT TYPE 2 DIABETES: INSIGHTS FROM THE DAPA-CKD TRIAL

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Niels Jong ◽  
Glenn Chertow ◽  
Fan Fan Hou ◽  
John McMurray ◽  
Ricardo Correa-Rotter ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Lower Risk ◽  
Urinary Albumin ◽  
Creatinine Ratio ◽  
Once Daily ◽  
Diabetes Status ◽  
Subgroup Analyses

Abstract Background and Aims Reductions in albuminuria are consistently associated with a subsequent lower risk of kidney failure. The sodium glucose co-transporter 2 inhibitor dapagliflozin significantly reduced albuminuria in patients with type 2 diabetes. Whether this effect persist in patients with chronic kidney disease (CKD) with and without diabetes is unknown. We therefore assessed and compared the effects of dapagliflozin on albuminuria in patients with CKD with and without type 2 diabetes from the DAPA-CKD trial. Method We randomized 4304 patients with CKD and an eGFR of 25-75 ml/min/1.73m2 and urinary albumin-to-creatinine ratio (UACR) 200-5000 mg/g to dapagliflozin (10 mg once daily) or placebo. Change in albuminuria was a pre-specified exploratory outcome. We used regression in UACR stage, defined as a transition from macroalbuminuria (≥300 mg/g) to micro- or normoalbuminuria (&lt;300 mg/g), and progression in UACR stage, defined as a transition from non-nephrotic (&lt;3000 mg/g) to nephrotic range albuminuria (≥3000 mg/g), as additional endpoints. Subgroup analyses were performed according to baseline type 2 diabetes status. Results Median (25th to 75th Percentile) UACR was 949 (477-1885) mg/g. In patients with and without type 2 diabetes baseline median UACR was 1017 mg/g and 861 mg/g, respectively. Dapagliflozin, compared to placebo, reduced UACR by 29.3% (95% confidence interval [CI] 25.2, 33.1; p&lt;0.001), with a 35.1% (95%CI 30.6, 39.4) reduction in patients with type 2 diabetes and 14.8% (95%CI 5.9, 22.9) reduction in patients without type 2 diabetes (p for interaction &lt;0.001). Among 3860 patients with UACR ≥300 mg/g at baseline, dapagliflozin significantly increased the likelihood of regression in UACR stage (hazard ratio [HR] 1.81; 95%CI 1.60, 2.05). The corresponding HRs for patients with and without type 2 diabetes were 2.06 (95%CI 1.78, 2.39) and 1.33 (95%CI 1.07, 1.66), respectively (p for interaction 0.001). Among 3820 patients with UACR &lt;3000 mg/g at baseline, dapagliflozin significantly decreased the risk of nephrotic range albuminuria (HR 0.41; 95%CI 0.32, 0.52). The corresponding HRs for patients with and without type 2 diabetes were 0.39 (95%CI 0.29, 0.51) and 0.50 (95%CI 0.30, 0.82), respectively (p for interaction 0.401). Conclusion In patients with CKD with and without type 2 diabetes dapagliflozin significantly reduced albuminuria, with a larger reduction in patients with type 2 diabetes. The similar effects of dapagliflozin on clinical outcomes in patients with or without type 2 diabetes, but different effects on UACR suggest that part of dapagliflozin’s protective effect in patients without diabetes is mediated through pathways unrelated to UACR reduction.

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

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
C Noergaard ◽  
C Torp-Pedersen ◽  
P Vestergaard ◽  
N Wong ◽  
T Gerds ◽  
...  
Keyword(s):  
Heart Failure ◽  
Type 2 Diabetes ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Lower Risk ◽  
Cox Regression ◽  
Receptor Agonists ◽  
All Cause Mortality ◽  
The Absolute

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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