409Cardiovascular risk profiles and outcomes in patients with type 2 diabetes - Implications for choice of new diabetes therapies

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
M E Malik ◽  
C A Andersson ◽  
P B Blanche ◽  
C M R Rasmussen ◽  
B Z Zareini ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Ischemic Stroke ◽  
Sglt2 Inhibitors ◽  
Low Risk ◽  
Receptor Agonists ◽  
Risk Of Death ◽  
History Of ◽  
New Onset

Abstract Background Reflecting recent clinical trial findings, updated type 2 diabetes (T2D) guidelines recommend targeting SGLT2 inhibitors at patients at risk of heart failure (HF)-related events and GLP-1 receptor agonists at those at greater risk of atherosclerotic events. However, which cardiovascular disease phenotype in patients with T2D is more predictive of one or other type of these events is unclear. Purpose To estimate the risk of HF-related events and atherosclerotic events, according to background cardiovascular phenotype, in patients with T2D. Methods Patients with T2D and new-onset cardiovascular disease were identified using Danish health care registers (period 1995 to 2015). Patients were divided in four groups based on the primary type of cardiovascular disease: 1) HF, 2) ischemic heart disease (IHD), 3) ischemic stroke, and 4) peripheral artery disease (PAD). The absolute 5-year risks of the subsequent event, either a HF-related event or an atherosclerotic event (IHD, ischemic stroke and PAD), and the associated risk of death, were compared across the four groups. The Aalen-Johansen estimator was used to account for censoring, the competing risk of HF and atherosclerotic events, respectively, and death. Results We included 37,850 patients with T2D and new-onset cardiovascular disease. Median age was 70 years and 40% were female. Patients with HF were at higher risk of readmission for HF (18.1%; 95% confidence interval (CI): 17.2–19.0) than of an atherosclerotic event (14.2%; 13.4–15.0) (Figure). Patients with IHD were at higher risk of a new atherosclerotic event (23.5%; 22.8.-24.2) than of developing HF (9.3%; 8.9–9.8), although the risk of HF was still substantial. Conversely, patients with ischemic stroke were at low risk of HF (3.3%; 2.9–3.8) and higher risk of an atherosclerotic event (16.9%; 95% CI: 16.0–17.7). Patients with PAD had the lowest risk of HF (3.1%; 95% CI: 2.8–3.4) and the highest risk of an atherosclerotic event (35.0%; 95% CI: 33.4–36.7). Compared to a new atherosclerotic event, developing HF was associated with a higher 1-year risk of death (16.0%; 95% CI: 14.7–17.3 versus 33.0%; 95% CI: 31.8–34.2) amongst all patients. Cumulative incidence of first new event Conclusions In T2D, a patient's history of cardiovascular disease was predictive of type of subsequent cardiovascular event. While history of ischemic stroke and PAD were associated with a high risk of future atherosclerotic events, and low risk of HF, patients with IHD were at substantial risk of both types of event. Conversely, while history of HF was most predictive of future HF events, the risk of atherosclerotic events in patients with HF was also high. Our findings may help determine which type of therapy T2D patients with a particular cardiovascular disease history might benefit from – SGLT2 inhibitors, GLP-1 receptor agonists or potentially both. Acknowledgement/Funding Mariam Elmegaard Malik was funded by a research grant from Department of Cardiology, Herlev and Gentofte Hospital.

scholarly journals Bitter sweet: Fournier’s Gangrene and SGLT2 inhibitors

2019 ◽  
Vol 9 (2) ◽  
pp. 52-54
Author(s):  
Coralea Kappel
Keyword(s):  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Diabetes Management ◽  
Fournier’S Gangrene ◽  
Sglt2 Inhibitors ◽  
Adverse Outcomes ◽  
Fournier's Gangrene ◽  
Risk Of Death ◽  
Increased Risk

Diabetes mellitus, especially type 2 is becoming the biggest epidemic of the 21st century affecting more than 415 million adults globally and expected to increase to more than 640 million adults by 2040. Patients with diabetes are at high risk for adverse outcomes, notably cardiovascular disease with an increased risk of death. In fact, the 2018 Canadian Diabetes Association (CDA) guidelines have updated the type 2 diabetes management algorithm; if the patient has clinical cardiovascular disease, an antihyperglycemic agent with demonstrated cardiovascular (CV) benefit should be added. There is a growing armamentarium of therapies with Health Canada-approved CV benefit include two from the sodium-glucose co-transporter 2 (SGLT2) inhibitors class namely Canagliflozin and empagliflozin. Despite their many advantages, the Food and Drug Administration (FDA) issued a black box warning for associated necrotizing fasciitis of the perineum in diabetes treated with SGLT2 inhibitors.  This case report highlights a case of Fournier’s gangrene (FG) in a male treated with empagliflozin for type 2 diabetes.

Visit-to-visit blood pressure variability in patients with type 2 diabetes with and without previous history of cardiovascular disease

2020 ◽  
Vol 38 (9) ◽  
pp. 1737-1744
Author(s):  
Maria Grazia Radaelli ◽  
Stefano Ciardullo ◽  
Silvia Perra ◽  
Rosa Cannistraci ◽  
Eleonora Bianconi ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Blood Pressure Variability ◽  
Previous History ◽  
History Of

Abstract P162: Comparison Of The Clinical Effect Of Empagliflozin On Glycemic And Non-glycemic Parameters In Japanese Patients With Type 2 Diabetes And Cardiovascular Disease Treated With Or Without Baseline Metformin

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Atsushi Tanaka ◽  
Koichi Node
Keyword(s):  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Troponin I ◽  
Treatment Guidelines ◽  
Geometric Mean ◽  
Sglt2 Inhibitors ◽  
Hypoglycemic Agents ◽  
Clinical Parameters ◽  
Diabetes Status

Introduction: Recent treatment guidelines for type 2 diabetes (T2D) recommend sodium-glucose cotransporter 2 (SGLT2) inhibitors to be considered preferentially in patients with T2D at high cardiovascular risk or with cardiovascular disease (CVD), regardless of their diabetes status and prior use of metformin. Hypothesis: We assessed the hypothesis that the therapeutic impact of SGLT2 inhibitors on clinical parameters differs according to the use of metformin. Methods: This was a post hoc analysis of the Effect of Empagliflozin on Endothelial Function in Cardiovascular High Risk Diabetes Mellitus: Multi-Center Placebo-Controlled Double-Blind Randomized (EMBLEM) trial. All participants (n=105; women 31.4%; mean age 64.8 years) had both T2D and DVD and were randomized to either 24 weeks of empagliflozin 10mg daily or placebo. We assessed the effect of empagliflozin on changes from baseline to 24 weeks in glycemic and non-glycemic clinical parameters, according to the baseline use of metformin. Results: Overall, 53 (50.5%) patients received baseline metformin. In the 52 patients treated with empagliflozin (48.1% with baseline metformin), the change from baseline systolic blood pressure was greater in patients receiving metformin, compared to metformin-naïve patients (group difference -8.5 [95%CI -17.7 to 0.6 mmHg], p=0.066). Reduction in body mass index was significantly greater in patients receiving baseline metformin, relative to nonusers (-0.54 [95%CI -1.07 to -0.01] kg/m 2 , p=0.047). The group ratio (baseline metformin users vs. nonusers) of proportional changes in the geometric mean of high-sensitivity Troponin-I was 0.74 (95%CI 0.59 to 0.92, p=0.009). No obvious difference was observed in glycemic parameters, such as fasting plasma glucose and HbA1c, between the baseline metformin users and nonusers. Conclusions: Our findings suggest empagliflozin has a partially different impact on clinical parameters according to whether or not metformin has been used at baseline. As clinical opportunities for prescribing SGLT2 inhibitors are likely to increase, further research is needed to investigate the effect of SGLT2 inhibitors on clinical parameters taking into account the background situation of hypoglycemic agents, such as metformin.

scholarly journals Comparative effects of sodium glucose cotransporter 2 (SGLT2) inhibitors and dipeptidyl peptidase-4 (DPP4) inhibitors on new-onset atrial fibrillation and stroke outcomes

2021 ◽  
Author(s):  
Sharen Lee ◽  
Jiandong Zhou ◽  
Carlin Chang ◽  
Tong Liu ◽  
Dong Chang ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Atrial Fibrillation ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Propensity Score ◽  
Lower Risk ◽  
Sglt2 Inhibitors ◽  
All Cause Mortality ◽  
New Onset

AbstractBackgroundSGLT2I and DPP4I are medications prescribed for type 2 diabetes mellitus patients. However, there are few population-based studies comparing their effects on incident atrial fibrillation or ischemic stroke.MethodsThis was a territory-wide cohort study of type 2 diabetes mellitus patients prescribed SGLT2I or DPP4I between January 1st, 2015 to December 31st, 2019 in Hong Kong. Patients with both DPP4I and SGLT2I use and patients with drug discontinuation were excluded. Patients with prior AF or stroke were excluded for the respective analysis. 1:2 propensity-score matching was conducted for demographics, past comorbidities and medications using nearest-neighbor matching method. Cox models were used to identify significant predictors for new onset heart failure (HF) or myocardial infarction (MI), cardiovascular and all-cause mortality.ResultsThe AF-free cohort included 49108 patients (mean age: 66.48 years old [SD: 12.89], 55.32% males) and the stroke-free cohort included 49563 patients (27244 males [54.96%], mean baseline age: 66.7 years old [SD: 12.97, max: 104.6 years old]). After propensity score matching, SGLT2i use was associated with a lower risk of new onset AF (HR: 0.43[0.28, 0.66]), cardiovascular mortality (HR: 0.79[0.58, 1.09]) and all-cause mortality (HR: 0.69[0.60, 0.79]) in the AF-free cohort. It was also associated with a lower risk of new onset stroke (0.46[0.33, 0.64]), cardiovascular mortality (HR: 0.74[0.55, 1.00]) and all-cause mortality (HR: 0.64[0.56, 0.74]) in the stroke-free cohort.ConclusionsThe novelty of our work si that SGLT2 inhibitors are protective against atrial fibrillation and stroke development for the first time. These findings should be validated in other cohorts.

Abstract 15526: Glucagon-like Peptide-1 Receptor Agonists Reduce Adverse Cardiovascular Disease (CVD) Events in Patients With Type 2 Diabetes: An Assessment of Heterogeneity Among CVD Outcomes and a Meta-regression Analysis

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Simran Grewal ◽  
Ninad Zaman ◽  
Louis Borgatta ◽  
Matthew Nudy ◽  
Brandon Peterson
Keyword(s):  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Cardiovascular Death ◽  
Nonfatal Stroke ◽  
Significant Heterogeneity ◽  
Receptor Agonists ◽  
Meta Regression ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Introduction: Recent evidence suggests glucagon-like peptide-1 receptor agonists (GLP-1 RA) reduce adverse cardiovascular disease (CVD) events. The objective of this study is to analyze randomized controlled trials (RCTs) testing GLP-1 RA’s effects on CVD among participants with type 2 diabetes (T2DM). Methods: RCTs comparing GLP-1 RA versus placebo among participants with T2DM were identified using PubMed and Cochrane databases. The endpoints of this analysis included major adverse cardiovascular events (MACE; a composite of cardiovascular death, nonfatal myocardial infarction (MI), and nonfatal stroke), and the individual components of MACE. The primary analysis calculated risk ratios (RR) and 95% confidence intervals (CI) for each endpoint. Heterogeneity for each endpoint was calculated using Chi 2 and I 2 tests. For any endpoint with significant heterogeneity, a meta-regression was performed using baseline hemoglobin A1C (A1C) in each RCT as the moderator and a R 2 value was calculated. Results: 7 RCTs (N = 56,004) were identified with 174,163 patient years of follow-up. GLP-1 RA reduced MACE [RR 0.89, 95% CI 0.83-0.95], cardiovascular death [RR 0.88, 95% CI 0.81-0.95], and nonfatal stroke [RR 0.85, 95% CI 0.77-0.94]. There was no significant heterogeneity among these RCTs (Figure 1). GLP-1 RA did not reduce nonfatal MI [RR 0.91, 95% CI 0.82-1.02]. However, there was significant heterogeneity among these RCTS (Chi 2 =12.94, p=0.04, I 2 =54%). When accounting for A1C in the regression model, there was no longer significant heterogeneity for this endpoint (p=0.23, I 2 =27%). A relationship between A1C and GLP-1 RA’s effect on nonfatal MI (R 2 =0.64, Figure 1) was observed when performing the meta-regression. Conclusion: GLP-1 RA reduced MACE, cardiovascular death, and nonfatal stroke in patients with T2DM with minimal heterogeneity among RCTs. GLP-1 RA did not reduce nonfatal MI, however there may be an association between A1C and GLP-1 RA’s effect on nonfatal MI.

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

2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Elvira D’Andrea ◽  
Aaron S. Kesselheim ◽  
Jessica M. Franklin ◽  
Emily H. 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 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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