Heterogeneity of antidiabetic treatment effect on the risk of major adverse cardiovascular events in type 2 diabetes: a systematic review and meta-analysis

Abstract Background We explored whether clinically relevant baseline characteristics of patients with type 2 diabetes can modify the effect of glucagon-like peptide-1 receptor agonists (GLP-1 RA) or sodium-glucose cotransporter-2 inhibitors (SGLT-2i) on the risk of major adverse cardiovascular events (MACE). Methods We investigated Medline and EMBASE through June 2019. We included randomized clinical trials reporting the effect of GLP-1 RA or SGLT-2i on MACE in subgroups of patients with type 2 diabetes, identified through key baseline factors: established cardiovascular disease; heart failure; chronic kidney disease; uncontrolled diabetes; duration of diabetes; hypertension; obesity; age; gender and race. Hazard ratios (HRs) and 95% confidence intervals (CIs) from trials were meta-analyzed using random-effects models. Results Ten trials enrolling 89,790 patients were included in the analyses. Subgroup meta-analyses showed a 14% risk reduction of MACE in patients with established cardiovascular disease [GLP1-RA: HR, 0.86 (95% CI, 0.80–0.93); SGLT-2i: 0.86 (0.80–0.93)], and no effect in at-risk patients without history of cardiovascular events [GLP1-RA: 0.94 (0.82–1.07); SGLT-2i: 1.00 (0.87–1.16)]. We observed a trend toward larger treatment benefits with SGLT-2i among patients with chronic kidney disease [0.82 (0.69–0.97)], and patients with uncontrolled diabetes for both GLP1-RA or SGLT-2i [GLP1-RA: 0.82 (0.71–0.95); SGLT-2i: 0.84 (0.75–0.95)]. Uncontrolled hypertension, obesity, gender, age and race did not appear to modify the effect of these drugs. Conclusions In this exploratory analysis, history of cardiovascular disease appeared to modify the treatment effect of SGLT2i or GLP1-RA on MACE. Chronic kidney disease and uncontrolled diabetes should be further investigated as potential effect modifiers.

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Heterogeneity of antidiabetic treatment effect on the risk of major adverse cardiovascular events in type 2 diabetes: a systematic review and meta-analysis

10.21203/rs.3.rs-30056/v1 ◽

2020 ◽

Author(s):

Elvira D'Andrea ◽

Aaron S. Kesselheim ◽

Jessica M. Franklin ◽

Emily Jung ◽

Spencer Phillips Hey ◽

...

Keyword(s):

Type 2 Diabetes ◽

Cardiovascular Disease ◽

Chronic Kidney Disease ◽

Kidney Disease ◽

Treatment Effect ◽

Cardiovascular Events ◽

Major Adverse Cardiovascular Events ◽

Uncontrolled Diabetes ◽

History Of

Abstract Background We explored whether clinically relevant baseline characteristics of patients with type 2 diabetes can modify the effect of glucagon-like peptide-1 receptor agonists (GLP-1 RA) or sodium-glucose cotransporter-2 inhibitors (SGLT-2i) on the risk of major adverse cardiovascular events (MACE). Methods We investigated Medline and EMBASE through June 2019. We included randomized clinical trials reporting the effect of GLP-1 RA or SGLT-2i on MACE in subgroups of patients with type 2 diabetes, identified through key baseline factors: established cardiovascular disease; heart failure; chronic kidney disease; uncontrolled diabetes; duration of diabetes; hypertension; obesity; age; gender and race. Hazard ratios (HRs) and 95% confidence intervals (CIs) from trials were meta-analyzed using random-effects models. Results Nine trials enrolling 87,143 patients were included in the analyses. Subgroup meta-analyses showed a 14% risk reduction of MACE in patients with established cardiovascular disease [GLP1-RA: HR, 0.86 (95% CI, 0.79–0.94); SGLT-2i: 0.86 (0.80–0.93)], and no effect in at-risk patients without history of cardiovascular events [GLP1-RA: 0.95 (0.83–1.08); SGLT-2i: 1.00 (0.87–1.16)]. We observed a trend toward larger treatment benefits with SGLT-2i among patients with chronic kidney disease [0.82 (0.69–0.97)], and patients with uncontrolled diabetes for both GLP1-RA or SGLT-2i [GLP1-RA: 0.82 (0.71–0.95); SGLT-2i: 0.84 (0.75–0.95)]. Uncontrolled hypertension, obesity, gender, age and race did not appear to modify the effect of these drugs. Conclusions In this exploratory analysis, history of cardiovascular disease appeared to modify the treatment effect of SGLT2i or GLP1-RA on MACE. Chronic kidney disease and uncontrolled diabetes should be further investigated as potential effect modifiers.

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Heterogeneity of antidiabetic treatment effect on the risk of major adverse cardiovascular events in type 2 diabetes: a systematic review and meta-analysis

10.21203/rs.3.rs-30056/v2 ◽

2020 ◽

Author(s):

Elvira D'Andrea ◽

Aaron S. Kesselheim ◽

Jessica M. Franklin ◽

Emily Jung ◽

Spencer Phillips Hey ◽

...

Keyword(s):

Type 2 Diabetes ◽

Cardiovascular Disease ◽

Chronic Kidney Disease ◽

Kidney Disease ◽

Treatment Effect ◽

Cardiovascular Events ◽

Major Adverse Cardiovascular Events ◽

Uncontrolled Diabetes ◽

History Of

Abstract Background We explored whether clinically relevant baseline characteristics of patients with type 2 diabetes can modify the effect of glucagon-like peptide-1 receptor agonists (GLP-1 RA) or sodium-glucose cotransporter-2 inhibitors (SGLT-2i) on the risk of major adverse cardiovascular events (MACE). Methods We investigated Medline and EMBASE through June 2019. We included randomized clinical trials reporting the effect of GLP-1 RA or SGLT-2i on MACE in subgroups of patients with type 2 diabetes, identified through key baseline factors: established cardiovascular disease; heart failure; chronic kidney disease; uncontrolled diabetes; duration of diabetes; hypertension; obesity; age; gender and race. Hazard ratios (HRs) and 95% confidence intervals (CIs) from trials were meta-analyzed using random-effects models. Results Nine trials enrolling 87,143 patients were included in the analyses. Subgroup meta-analyses showed a 14% risk reduction of MACE in patients with established cardiovascular disease [GLP1-RA: HR, 0.86 (95% CI, 0.79-0.94); SGLT-2i: 0.86 (0.80-0.93)], and no effect in at-risk patients without history of cardiovascular events [GLP1-RA: 0.95 (0.83-1.08); SGLT-2i: 1.00 (0.87-1.16)]. We observed a trend toward larger treatment benefits with SGLT-2i among patients with chronic kidney disease [0.82 (0.69-0.97)], and patients with uncontrolled diabetes for both GLP1-RA or SGLT-2i [GLP1-RA: 0.82 (0.71-0.95); SGLT-2i: 0.84 (0.75-0.95)]. Uncontrolled hypertension, obesity, gender, age and race did not appear to modify the effect of these drugs. Conclusions In this exploratory analysis, history of cardiovascular disease appeared to modify the treatment effect of SGLT2i or GLP1-RA on MACE. Chronic kidney disease and uncontrolled diabetes should be further investigated as potential effect modifiers.

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Distribution of cardiovascular disease and retinopathy in patients with type 2 diabetes according to different classification systems for chronic kidney disease: a cross-sectional analysis of the renal insufficiency and cardiovascular events (RIACE) Italian multicenter study

Cardiovascular Diabetology ◽

10.1186/1475-2840-13-59 ◽

2014 ◽

Vol 13 (1) ◽

pp. 59 ◽

Cited By ~ 16

Author(s):

Giuseppe Pugliese ◽

Anna Solini ◽

Enzo Bonora ◽

Emanuela Orsi ◽

Gianpaolo Zerbini ◽

...

Keyword(s):

Type 2 Diabetes ◽

Cardiovascular Disease ◽

Chronic Kidney Disease ◽

Kidney Disease ◽

Renal Insufficiency ◽

Cardiovascular Events ◽

Classification Systems ◽

Cross Sectional ◽

Sectional Analysis

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Letter by Tampakis et al Regarding Article, “Empagliflozin and Clinical Outcomes in Patients With Type 2 Diabetes Mellitus, Established Cardiovascular Disease, and Chronic Kidney Disease”

Circulation ◽

10.1161/circulationaha.117.032720 ◽

2018 ◽

Vol 138 (8) ◽

pp. 848-849 ◽

Cited By ~ 1

Author(s):

Athanasios Tampakis ◽

Ekaterini Christina Tampaki ◽

Lorenz Gürke

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Cardiovascular Disease ◽

Chronic Kidney Disease ◽

Type 2 Diabetes Mellitus ◽

Kidney Disease ◽

Clinical Outcomes

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CL1 ASSOCIATION BETWEEN DIABETES MEDICATION USE AND CARDIOVASCULAR EVENTS AMONG TYPE 2 DIABETES PATIENTS WITH ADVANCED CHRONIC KIDNEY DISEASE: A NATIONWIDE COHORT STUDY.

Value in Health ◽

10.1016/j.jval.2019.09.053 ◽

2019 ◽

Vol 22 ◽

pp. S407

Author(s):

H.C. Chang ◽

H.M. Cheng ◽

P.Y. Chang ◽

C.E. Chiang ◽

Y.W. Tsai

Keyword(s):

Type 2 Diabetes ◽

Chronic Kidney Disease ◽

Cohort Study ◽

Kidney Disease ◽

Cardiovascular Events ◽

Medication Use ◽

Advanced Chronic Kidney Disease ◽

Diabetes Medication ◽

Diabetes Patients

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Effect of Bariatric Surgery on Diagnosed Chronic Kidney Disease and Cardiovascular Events in Patients with Insulin-treated Type 2 Diabetes: a Retrospective Cohort Study from a Large UK Primary Care Database

Obesity Surgery ◽

10.1007/s11695-019-04201-y ◽

2020 ◽

Vol 30 (5) ◽

pp. 1685-1695 ◽

Cited By ~ 2

Author(s):

Mohammed Alkharaiji ◽

Uchenna Anyanwagu ◽

Richard Donnelly ◽

Iskandar Idris

Keyword(s):

Type 2 Diabetes ◽

Bariatric Surgery ◽

Primary Care ◽

Chronic Kidney Disease ◽

Cohort Study ◽

Kidney Disease ◽

Cardiovascular Events ◽

Retrospective Cohort ◽

Care Database

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Finerenone and Cardiovascular Outcomes in Patients with Chronic Kidney Disease and Type 2 Diabetes

Circulation ◽

10.1161/circulationaha.120.051898 ◽

2020 ◽

Cited By ~ 1

Author(s):

Gerasimos Filippatos ◽

Stefan D. Anker ◽

Rajiv Agarwal ◽

Bertram Pitt ◽

Luis M. Ruilope ◽

...

Keyword(s):

Heart Failure ◽

Type 2 Diabetes ◽

Chronic Kidney Disease ◽

Kidney Disease ◽

Renin Angiotensin System ◽

Mineralocorticoid Receptor Antagonist ◽

Angiotensin System ◽

Renin Angiotensin ◽

History Of

Background: The FIDELIO-DKD trial evaluated the effect of the nonsteroidal, selective mineralocorticoid receptor antagonist finerenone on kidney and cardiovascular (CV) outcomes in patients with chronic kidney disease (CKD) and type 2 diabetes (T2D) with optimized renin-angiotensin system blockade. Compared with placebo, finerenone reduced the composite kidney and CV outcomes. We report the effect of finerenone on individual CV outcomes and in patients with and without history of atherosclerotic CV disease (CVD). Methods: This randomized, double-blind, placebo-controlled trial included patients with T2D and urine albumin-to-creatinine ratio 30-5000 mg/g and an estimated glomerular filtration rate (eGFR) ≥25-<75 mL/min/1.73 m 2 , treated with optimized renin-angiotensin system blockade. Patients with a history of heart failure with reduced ejection fraction were excluded. Patients were randomized 1:1 to receive finerenone or placebo. The composite CV outcome included time to CV death, myocardial infarction, stroke, or hospitalization for heart failure. Prespecified CV analyses included analyses of the components of this composite and outcomes according to CVD history at baseline. Results: Between September 2015 and June 2018, 13,911 patients were screened and 5674 were randomized; 45.9% of patients had CVD at baseline. Over a median follow-up of 2.6 years (interquartile range, 2.0-3.4 years), finerenone reduced the risk of the composite CV outcome compared with placebo (hazard ratio [HR], 0.86; 95% confidence interval [CI], 0.75-0.99; P=0.034), with no significant interaction between patients with and without CVD (HR, 0.85; 95% CI, 0.71-1.01 in patients with a history of CVD; HR, 0.86; 95% CI, 0.68-1.08 in patients without a history of CVD; P-value for interaction, 0.85). The incidence of treatment-emergent adverse events was similar between treatment arms, with a low incidence of hyperkalemia-related permanent treatment discontinuation (2.3% with finerenone vs 0.8% with placebo in patients with CVD and 2.2% with finerenone vs 1.0% with placebo in patients without CVD). Conclusions: Among patients with CKD and T2D, finerenone reduced incidence of the composite CV outcome, with no evidence of differences in treatment effect based on pre-existing CVD status. Clinical Trial Registration: URL: https://clinicaltrials.gov Unique Identifier: NCT02540993 (Funded by Bayer AG)

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