Cardiovascular Outcomes In Type Research Articles

Role of endogenous GLP-1 on arterial stiffness and renal haemodynamics following bariatric surgery.

Cardiovascular trials have revealed the positive impact of GLP-1 receptor agonists (GLP-1 RAs) on cardiovascular outcomes in type 2 diabetes (T2D). However, the specific effects of endogenous GLP-1 on arterial stiffness and renal function remain understudied. This study aimed to explore the influence of endogenous GLP-1 response post-bariatric surgery on arterial stiffness and renal haemodynamic. Thirty individuals with morbid obesity and without T2D, scheduled for Roux-en-Y Gastric Bypass (RYGB), were included. Clinical parameters, 3-hour oral glucose tolerance test (OGTT) with serial sampling for glycaemia, GLP-1 and insulin, carotid-femoral pulse wave velocity (cf-PWV), carotid distensibility coefficient (carotid-DC) and renal resistive index (RRI) measurements were conducted pre-surgery and 1-year post-surgery. Participants were categorized into high-response and low-response groups based on their post-surgery increase in GLP-1 (median increase of 104% and 1%, respectively, pre- vs. post-surgery). Post-surgery, high-response group demonstrated a greater reduction in cf-PWV (p = .033) and a greater increase (p = .043) in carotid DC compared to low-response group. These enhancements were observed independently of weight loss or blood pressure changes. High-response group exhibited a reduction in RRI (p = .034), although this association was influenced by improvement in pulse pressure. Finally, a multivariate stepwise regression analysis indicated that the percentage increase of GLP1, Δ-GLP1(AUC)%, was the best predictor of percentage decrease in cf-PWV (p = .014). Elevated endogenous GLP-1 response following RYGB was associated with improved arterial stiffness and renal resistances, suggesting potential cardio-renal benefits. The findings underscore the potential role of endogenous GLP-1 in influencing vascular and renal haemodynamics independent of traditional weight loss.

Association of single-point insulin sensitivity estimator index (SPISE) with future cardiovascular outcomes in patients with type 2 diabetes.

To investigate the association of single-point insulin sensitivity estimator (SPISE) index with future cardiovascular outcomes in patients with type 2 diabetes. SPISE index (= 600 × high-density lipoprotein cholesterol [mg/dL]0.185/triglycerides [mg/dL]0.2 × body mass index [kg/m2]1.338) was calculated in 10 190 participants. Cox proportional hazard regression models were applied to evaluate the association between SPISE index and future cardiovascular outcomes. Restricted cubic spline analyses and two-piecewise linear regression models were employed to explore the nonlinear association and to determine the threshold value. Subgroup and interaction analyses were conducted to test the robustness of the results. After fully adjusting for well-established metabolic confounders, higher SPISE index was significantly associated with lower risk of future cardiovascular outcomes in patients with type 2 diabetes (major adverse cardiovascular event [MACE]): hazard ratio [HR] 0.94, 95% confidence interval [CI] 0.90-0.98, p = 0.0026; overall mortality: HR 0.90, 95% CI 0.86-0.93, p < 0.0001; cardiovascular disease [CVD] mortality: HR 0.85, 95% CI 0.79-0.92, p < 0.0001; congestive heart failure (CHF): HR 0.72, 95% CI 0.67-0.78, p < 0.0001; major coronary events: HR 0.91, 95% CI 0.87-0.95, p < 0.0001. There was a nonlinear association between SPISE index and future cardiovascular outcomes (the threshold value was 5.68 for MACE, 5.71 for overall mortality, 4.64 for CVD mortality, 4.48 for CHF, and 6.09 for major coronary events, respectively). Higher SPISE index was independently associated with lower risk of future cardiovascular outcomes in type 2 diabetes patients after full adjustment for well-established metabolic confounders.

The effect of dapagliflozin use on cardiovascular outcomes in type 2 diabetic patients hospitalized with COVID-19

The effect of dapagliflozin use on cardiovascular outcomes in type 2 diabetic patients hospitalized with COVID-19

Comparison of sodium-glucose co-transporter-2 inhibitors and glucagon-like peptide-1 receptor agonists in myocardial infarction patients with type 2 diabetes

Abstract Background Both sodium–glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP1-RA) have been shown to reduce the risk of adverse cardiovascular outcomes in type 2 diabetes mellitus (T2DM) patients with established atherosclerotic cardiovascular disease. Purpose The aim of this study was to assess the comparative effectiveness of SGLT2i and GLP1-RA in myocardial infarction (MI) patients with T2DM. Methods This observational cohort study included MI patients with T2DM who were treated with SGLT2i or GLP1-RA within 180 days of hospital discharge between 2013 and 2021. Data was acquired from the SWEDEHEART registry, a nationwide quality register. The co-primary endpoints of this study were a composite of MI, ischemic stroke and all-cause mortality (MACE) and a composite of heart failure hospitalisation (HHF) and all-cause mortality. Inverse probability of treatment weighting was used to adjust for differences in baseline covariates between the treatment groups. Results This study consisted of 617 patients who were treated with SGLT2i and 543 patients who were treated with GLP1-RA. We observed no statistically significant differences between SGLT2i and GLP1-RA concerning the risk of MACE (adjusted incidence rate 76 vs. 68 events per 1000 person-years; HR 1.09 [95% CI 0.85 - 1.40]) and the risk of HHF or all-cause mortality (adjusted incidence rate 52 vs. 50 events per 1000 person-years; HR 1.04 [95% CI 0.80 - 1.36]). Similarly, we did not observe any statistically significant differences between the treatment groups concerning the secondary outcomes of MI (adjusted incidence rate 63 vs. 53 events per 1000 person-years; HR 1.08 [95% CI 0.83 - 1.40]), stroke (adjusted incidence rate 7 vs. 6 events per 1000 person-years; HR 1.22 [95% CI 0.57 - 2.87]), HHF (adjusted incidence rate 45 vs. 38 events per 1000 person-years; HR 1.06 [95% CI 0.80 - 1.41]) and all-cause mortality (adjusted incidence rate 11 vs. 15 events per 1000 person-years; HR 1.06 [95% CI 0.63 - 1.82]). Conclusions There were no statistically significant differences between SGLT2i and GLP1-RA concerning the risk of recurrent ischemic events, HHF and all-cause mortality in this cohort of MI patients with T2DM.Cumulative incidence of events

GLP-1 Receptor Agonist Therapy With and Without SGLT2 Inhibitors in Patients With Type 2 Diabetes

BackgroundSodium-glucose cotransporter-2 (SGLT2) inhibitors and GLP-1 receptor agonists (GLP-1 RAs) reduce adverse cardiovascular outcomes in type 2 diabetes (T2D). However, the efficacy of combination therapy is unclear. ObjectivesThe aim of this study was to evaluate the effects of GLP-1 RAs on cardiovascular outcomes in patients with T2D treated with or without SGLT2 inhibitors. MethodsPost hoc analysis of Harmony Outcomes (Albiglutide and Cardiovascular Outcomes in Patients With Type 2 Diabetes and Cardiovascular Disease) evaluating the effect of albiglutide in T2D with cardiovascular disease by background SGLT2 inhibitor use. Additionally, a trial-level meta-analysis of Harmony Outcomes and AMPLITUDE-O (Effect of Efpeglenatide on Cardiovascular Outcomes), which evaluated T2D with cardiovascular or renal disease, was performed, combining the treatment effect estimates according to SGLT2 inhibitor use. ResultsOf the 9,462 participants in Harmony Outcomes, 575 (6.1%) were treated with SGLT2 inhibitors at baseline. The effect of albiglutide on reducing the composite of cardiovascular death, myocardial infarction, or stroke (major adverse cardiovascular events) was consistent with or without SGLT2 inhibitors (P interaction = 0.70). The effect of albiglutide on secondary outcomes and adverse events was not modified by SGLT2 inhibitors. A meta-analysis of Harmony Outcomes and AMPLITUDE-O included 13,538 patients, of whom 1,193 (8.8%) used SGLT2 inhibitors. Compared to placebo, GLP1-RAs reduced major adverse cardiovascular events without effect modification by SGLT2 inhibitor use (HR: 0.77; 95% CI: 0.68-0.87 without SGLT2 inhibitors; and HR: 0.78; 95% CI: 0.49-1.24 with SGLT2 inhibitors) (P for interaction = 0.95) and reduced heart failure hospitalization (HR: 0.72; 95% CI: 0.55-0.92 vs HR: 0.34; 95% CI: 0.12-0.96) (P for interaction = 0.18). ConclusionsIn patients with T2D and cardiovascular disease, GLP-1 RAs reduced cardiovascular events independently of SGLT2 inhibitor use. These findings suggest that the combination of GLP-1 RAs with SGLT2 inhibitors may further reduce cardiovascular risk. Clinical trials with combination therapy are needed.

Comparative cardiovascular outcomes in type 2 diabetes patients taking dapagliflozin versus empagliflozin: a nationwide population-based cohort study

BackgroundSodium-glucose co-transporter-2 inhibitors displayed cardiovascular benefits in type 2 diabetes mellitus in previous studies; however, there were some heterogeneities regarding respective cardiovascular outcomes within the class. Furthermore, their efficacies in Asians, females, and those with low cardiovascular risks were under-represented. Thus, we compared the cardiovascular outcomes between new users of dapagliflozin and empagliflozin in a broad range of patients with type 2 diabetes mellitus using a nationwide population-based real-world cohort from Korea.MethodsKorean National Health Insurance registry data between May 2016 and December 2018 were extracted, and an active-comparator new-user design was applied. The primary outcome was a composite of heart failure (HF)-related events (i.e., hospitalization for HF and HF-related death), myocardial infarction, ischemic stroke, and cardiovascular death. The secondary outcomes were individual components of the primary outcome.ResultsA total of 366,031 new users of dapagliflozin or empagliflozin were identified. After 1:1 nearest-neighbor propensity score matching, 72,752 individuals (mean age approximately 56 years, 42% women) from each group were included in the final analysis, with a follow-up of 150,000 ~ person-years. Approximately 40% of the patients included in the study had type 2 diabetes mellitus as their sole cardiovascular risk factor, with no other risk factors. The risk of the primary outcome was not different significantly between dapagliflozin and empagliflozin users (hazard ratio [HR] 0.93, 95% confidence interval [CI] 0.855–1.006). The risks of secondary outcomes were also similar, with the exception of the risks of HF-related events (HR 0.84, 95% CI 0.714–0.989) and cardiovascular death (HR 0.76, 95% CI 0.618–0.921), which were significantly lower in the dapagliflozin users.ConclusionsThis large-scale nationwide population-based real-world cohort study revealed no significant difference in composite cardiovascular outcomes between new users of dapagliflozin and empagliflozin. However, dapagliflozin might be associated with lower risks of hospitalization or death due to HF and cardiovascular death than empagliflozin in Asian patients with type 2 diabetes mellitus.

Global trends and focuses of GLP-1RA in renal disease: a bibliometric analysis and visualization from 2005 to 2022.

Glucagon-like peptide 1 receptor agonist (GLP-1RA) is a new class of glucose-lowing agents with the kidney benefit effect. This paper aims at finding the current state and hotspots of the research on GLP-1RA in kidney disease by using bibliometric methodologies and visualization maps to analyze publications and provide the direction for future studies on that topic. Literature information was obtained by retrieving the WoSCC database. Then, software like Microsoft Excel, VOSviewer, and CiteSpace was used to analyze and process obtained data. Bibliometric analysis and visualization of nations, authors, organizations, journals, keywords, and references were also done by VOSviewer and CiteSpace. A total of 991 publications written by 4747 authors from 1637 organizations in 75 countries on GLP-1RA in renal disease in Web of Science Core Collection were retrieved. The number of publications and citations kept growing from 2015 to 2022. The USA, Univ Copenhagen, and Rossing Peter are the leading country, organization, and author on this topic, respectively. All literature was published in 346 journals, and DIABETES OBESITY & METABOLISM is the journal with the most contributions. Meanwhile, most references are from DIABETES CARE. "Cardiovascular outcome" is the most frequent keyword in the total publications, and the reference cited most times is "Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes" by Marso SP. The topic of GLP-1RA in renal disease has attracted more and more attention all over the world. Existing studies are mainly about clinical use in patients with diabetes, and studies on the mechanism are lacking.

200-LB: Benefit of Dual Therapy with GLP-1 RA and SGLT2i on Cardiovascular Outcomes in Type 2 Diabetes

Background: Evidence on the cardiovascular benefit of dual glucagon like peptide-1 receptor agonist (GLP-1 RA) and sodium-glucose co-transporter-2 inhibitor (SGLT2i) therapy is lacking. Aim: To compare the benefit of dual GLP-1 RA and SGLT2i therapy to other dual type 2 diabetes therapies with respect to heart failure and major cardiovascular adverse events (MACE). Methods: From 2010-2021 patients from the Danish nationwide registries were followed from start of dual second-line type 2 diabetes treatment. Primary outcome was heart failure, and secondary outcomes were MACE and all-cause death. The estimated risk following 1 of 4 dual therapy combinations was determined using a longitudinal causal inference framework assuming all patients followed one dual therapy for 5 years. Results: A total of 87,201 persons were included (GLP-1 RA and SGLT2i: 14,831, GLP-1 RA and DPP4/SU/TZD: 20,417, SGLT2i and DPP4/SU/TZD: 22,803, dual DPP4/SU/TZD: 29,150). The 5-year risk ratio (95% CI) of dual GLP-1 RA and SGLT2i therapy compared to reference (dual DPP4/SU/TZD) for heart failure was: 0.93 (0.87;1.00), for MACE: 0.91 (0.87;0.95) and for all cause death: 0.78 (0.74;0.82), see Figure. Conclusion: Dual therapy with GLP-1 RA and SGLT2i showed a benefit on heart failure compared to other dual therapies. Dual therapy with GLP-1 RA and SGLT2i showed a benefit on MACE and all-cause death compared to the reference treatment. Disclosure B. Zareini: None. T. A. Gerds: None. K. K. Sørensen: None. K. K. B. Clemmensen: Employee; Novo Nordisk A/S, Stock/Shareholder; Novo Nordisk A/S. K. Kvist: Employee; Novo Nordisk A/S. J. David: Employee; Novo Nordisk A/S, Sanofi. C. Torp-pedersen: Research Support; Novo Nordisk, Bayer Inc.

Cerebrovascular, Cognitive and Cardiac Benefits of SGLT2 Inhibitors Therapy in Patients with Atrial Fibrillation and Type 2 Diabetes Mellitus: Results from a Global Federated Health Network Analysis.

Sodium-glucose co-transporter 2 inhibitors (SGLT2i) are effective anti-diabetic drugs improving cardiovascular outcomes in type 2 diabetes mellitus (T2DM) patients. This study investigated cardiovascular, cerebrovascular and cognitive outcomes of SGLT2i therapy in patients with atrial fibrillation (AF) and T2DM. Observational study using TriNetX, a global health research network of anonymised electronic medical records from real-world patients between January 2018 and December 2019. The network includes healthcare organisations globally but predominately in the United States. AF patients (ICD-10-CM code: I48) with T2DM were divided according to SGLT2i use or not, and balanced using propensity score matching (PSM). Patients were followed-up for 3-years. The primary endpoints were ischaemic stroke/transient ischemic attack (TIA), intracranial haemorrhage (ICH), and incident dementia. Secondary endpoints were incident heart failure and mortality. We identified 89,356 AF patients with T2DM of which 5061 (5.7%) were taking a SGLT2i. After PSM, 5049 patients (mean age 66.7 ± 10.6 years; 28.9% female) were included in each group. At 3-years follow-up, the risk of ischaemic stroke/TIA was higher in patients not receiving SGLT2i (HR 1.12, 95% CI 1.01-1.24) and for ICH (HR 1.57, 95% CI 1.25-1.99) and incident dementia (HR 1.66, 95% CI 1.30-2.12). Incident heart failure (HR 1.50, 95% CI 1.34-1.68) and mortality (HR 1.77, 95% CI 1.58-1.99) risks were increased in AF patients not receiving SGLT2i. In our large 'real world' analysis of patients with concomitant AF and T2DM, SGLT2i reduced the risk of cerebrovascular events, incident dementia, heart failure and death.

Risk of stroke and retinopathy during GLP-1 receptor agonist cardiovascular outcome trials: An eight RCTs meta-analysis.

To explore the risk of stroke (including ischemic and hemorrhagic stroke) in type 2 diabetes mellitus treated with glucagon-like peptide 1 receptor agonist (GLP-1RA) medication according to data from the Cardiovascular Outcome Trials(CVOT). Randomized controlled trials (RCT) on GLP-1RA therapy and cardiovascular outcomes in type 2 diabetics published in full-text journal databases such as Medline (via PubMed), Embase, Clinical Trials.gov, and the Cochrane Library from establishment to May 1, 2022 were searched. We assess the quality of individual studies by using the Cochrane risk of bias algorithm. RevMan 5.4.1 software was use for calculating meta- analysis. A total of 60,081 randomized participants were included in the data of these 8 GLP-1RA cardiovascular outcomes trials. Pooled analysis reported statistically significant effect on total stroke risk[RR=0.83, 95%CI(0.73, 0.95), p=0.005], and its subtypes such as ischemic Stroke [RR=0.83, 95%CI(0.73, 0.95), p=0.008] from treatment with GLP-1RA versus placebo, and have no significant effect on the risk of hemorrhagic stroke[RR=0.83, 95%CI(0.57, 1.20), p=0.31] and retinopathy [RR=1.54, 95%CI(0.74, 3.23), p=0.25]. GLP-1RA significantly reduces the risk of ischemic stroke in type 2 diabetics with cardiovascular risk factors.

Impact of SGLT2 inhibitor on mortality and cardiovascular outcomes in patients with type 2 diabetes mellitus with left main or multivessel coronary artery disease

Abstract Background Sodium-glucose Cotransporter 2 inhibitors (SGLT2-i) have shown improved cardiovascular outcomes in type 2 diabetes mellitus (T2DM) that surpass their hypoglycaemic power. However, the inclusion criteria in the pivotal studies were broad in terms of cardiovascular disease, and there are no specific studies on patients with coronary artery disease (CAD). Purpose To compare, in patients with T2DM and extensive CAD, the hazard ratio (HR) of all-cause death in patients treated with or without SLGT2-I, adjusted by IPTW and treatment (revascularization) strategy. Secondary: To compare the adjusted HR of cardiovascular (CV) death, myocardial infarction (MI), stroke, or heart failure admission (HF) in patients treated with or without SLGT-I. Methods A single-centre retrospective observational study in patients with T2DM, with the first diagnosis of extensive CAD defined by &amp;gt;50% stenosis in LM or 3-vessels, and alive at discharge. The study was approved by the research ethics committee and recruited consecutive patients from 2015 (year of first SLGT2-I approval) to 2020. Patients with prior revascularization, severe renal failure (filtration rate &amp;lt;30 ml/min), less than 6 months of SLGT2-I treatment and less than 1 year of follow-up were excluded. Results We recruited 420 patients with a mean age of 71.2±11.1 years; 78.6% were male, 82.6% had hypertension, 72% hyperlipemia, 50.2% were smokers or former smokers, 52.9% had a history of previous myocardial infarction and 10.7% of stroke. Mean LVEF (%) was 51.5±1.5, creatinine clearance 73.94±22 ml/min and glycated haemoglobin (%) 7.3±1.2. The presentation was acute coronary syndrome in 44.3% (27% ST elevation/73% non-ST elevation). LM was affected in 29%; 3-vessel CAD was found in 86.7%; 2-vessel in 8.3%; 1-vessel in 3.8%, and 1.2% exclusively in the LM. Treatment strategy was PCI + OMT in 48.3%, CABG + OMT 39.8% and OMT only in 21.9%. T2DM treatment, secondary prevention treatment and metabolic control at follow up are presented in Table 1. A total of 104 patients (24.8%) started treatment with SGLT2-I during a mean of 1.6±1 years. At a mean follow-up of 3±1.6 years, mortality was 16.4%, CV mortality was 9.5%, 6.9% had a MI,3.3% had a stroke, and 11.4% had HF admission. Patients treated with SLGT2-I had a lower risk of all-cause death, cardiovascular death and the composite of CV death or HF (Table 2). After IPTW, the risk of all-cause death was persistently lower in the SLGT-I group Conclusion This real-life study found that in T2DM patients with LM or MVD only 1 out of 4 patients was treated with SGLT2-I as a part of their secondary prevention treatment. Those with SGLT2-I had a reduced risk of all-cause death (HR 0.34 [0.12–0.91], p=0,033) after IPTW and treatment (revascularization) strategy adjustment. Funding Acknowledgement Type of funding sources: None.

Time-resolved trajectory of glucose lowering medications and cardiovascular outcomes in type 2 diabetes: a recurrent neural network analysis

AimTreatment algorithms define lines of glucose lowering medications (GLM) for the management of type 2 diabetes (T2D), but whether therapeutic trajectories are associated with major adverse cardiovascular events (MACE) is unclear. We explored whether the temporal resolution of GLM usage discriminates patients who experienced a 4P-MACE (heart failure, myocardial infarction, stroke, death for all causes).MethodsWe used an administrative database (Veneto region, North-East Italy, 2011–2018) and implemented recurrent neural networks (RNN) with outcome-specific attention maps. The model input included age, sex, diabetes duration, and a matrix of GLM pattern before the 4P-MACE or censoring. Model output was discrimination, reported as area under receiver characteristic curve (AUROC). Attention maps were produced to show medications whose time-resolved trajectories were the most important for discrimination.ResultsThe analysis was conducted on 147,135 patients for training and model selection and on 10,000 patients for validation. Collected data spanned a period of ~ 6 years. The RNN model efficiently discriminated temporal patterns of GLM ending in a 4P-MACE vs. those ending in an event-free censoring with an AUROC of 0.911 (95% C.I. 0.904–0.919). This excellent performance was significantly better than that of other models not incorporating time-resolved GLM trajectories: (i) a logistic regression on the bag-of-words encoding all GLM ever taken by the patient (AUROC 0.754; 95% C.I. 0.743–0.765); (ii) a model including the sequence of GLM without temporal relationships (AUROC 0.749; 95% C.I. 0.737–0.761); (iii) a RNN model with the same construction rules but including a time-inverted or randomised order of GLM. Attention maps identified the time-resolved pattern of most common first-line (metformin), second-line (sulphonylureas) GLM, and insulin (glargine) as those determining discrimination capacity.ConclusionsThe time-resolved pattern of GLM use identified patients with subsequent cardiovascular events better than the mere list or sequence of prescribed GLM. Thus, a patient’s therapeutic trajectory could determine disease outcomes.

Effects of GLP-1 receptor agonists on arrhythmias and its subtypes in patients with type 2 diabetes: A systematic review and meta-analysis.

PurposeAn update of a systematic review and meta-analysis of the risk of arrhythmias and their subtypes in type 2 diabetic patients receiving glucagon-like peptide 1 receptor agonist (GLP-1RA) medication according to data from the Cardiovascular Outcome Trial(CVOT).MethodsRandomized controlled trials (RCT) on GLP-1RA therapy and cardiovascular outcomes in type 2 diabetes mellitus patients published in full-text journal databases such as MEDLINE (via PubMed), Embase, Clinical Trials.gov, and the Cochrane Library from establishment to March 1, 2022 were searched. We assessed the quality of individual studies by the Cochrane risk-of-bias algorithm. RevMan 5.4.1 software was use for calculating meta-analysis.ResultsA total of 60,081 randomized participants were included in the data of these 8 GLP-1RA cardiovascular outcomes trials. Pooled analysis reported no significant effect on total arrhythmia [RR=0.96, 95% CI (0.96, 1.05), p =0.36], and its subtypes such as atrial fibrillation [RR=0.96, 95% CI (0.86, 1.07), p =0.43], atrial flutter [RR= 0.82, 95% CI (0.57, 1.19), p =0.30], atrial tachycardia [RR=0.64, 95% CI (0.20, 2.01), p =0.44)], sinoatrial node dysfunction [RR=0.74, 95% CI (0.44, 1.25), p =0.26], ventricular preterm systole [RR=1.42, 95% CI (0.62, 3.26), p =0.41], second degree AV block [RR=0.96, 95% CI (0.53, 1.72), p =0.88], complete AV block [RR=0.75, 95% CI (0.49, 1.17), p =0.21], ventricular fibrillation [RR=1.00, 95% CI (0.50, 2.02), p =1.00], ventricular tachycardia [RR=1.37, 95% CI (0.91, 2.08), p =0.13] from treatment with GLP-1RA versus placebo. However, the risk of hypoglycemia was reduced by about 30% [RR=0.70, 95% CI (0.57, 0.87), p=0.001] and the risk of pneumonia by about 25% [RR=0.85, 95% CI (0.75, 0.97), p=0.01], both statistically significant differences.ConclusionIn type 2 diabetic patients, treatment with GLP-1RA has no significant effect on the risk of major arrhythmias but significantly reduces the risk of hypoglycemia and pneumonia.

Remnant Cholesterol and Its Visit-to-Visit Variability Predict Cardiovascular Outcomes in Patients With Type 2 Diabetes: Findings From the ACCORD Cohort

OBJECTIVERemnant cholesterol (remnant-C) predicts atherosclerotic cardiovascular disease, regardless of LDL-cholesterol (LDL-C) levels. This study assessed the associations between remnant-C and cardiovascular outcomes in type 2 diabetes.RESEARCH DESIGN AND METHODSThis post hoc analysis of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial used patient (type 2 diabetes >3 months) remnant-C and major adverse cardiovascular event (MACE) data from the study database. The associations between remnant-C and MACEs were evaluated using Cox proportional hazards regression analyses. We examined the relative MACE risk in remnant-C versus LDL-C discordant/concordant groups using clinically relevant LDL-C targets by discordance analyses.RESULTSThe baseline analysis included 10,196 participants, with further visit-to-visit variability analysis including 9,650 participants. During follow-up (median, 8.8 years), 1,815 patients (17.8%) developed MACEs. After adjusting for traditional cardiovascular risk factors, each 1-SD increase in remnant-C was associated with a 7% higher MACE risk (hazard ratio [HR] 1.07, 95% CI 1.02–1.12, P = 0.004). In the fully adjusted model, the visit-to-visit remnant-C variability calculated using logSD (HR 1.41, 95% CI 1.18–1.69, P < 0.001) and logARV (HR 1.45, 95% CI 1.22–1.73, P < 0.001) was associated with MACEs. Residual lipid risk (remnant-C ≥31 mg/dL) recognized individuals at a higher MACE risk, regardless of LDL-C concentrations. Within each LDL-C subgroup (>100 or ≤100 mg/dL), high baseline remnant-C was associated with a higher MACE risk (HR 1.37, 95% CI 1.09–1.73, P = 0.007; HR 1.22, 95% CI 1.04–1.41, P = 0.015, respectively).CONCLUSIONSRemnant-C levels were associated with MACEs in patients with type 2 diabetes independent of LDL-C, and visit-to-visit remnant-C variability helped identify those with higher cardiovascular risk.

424-P: Body-Weight Variability and Risk of Cardiovascular Outcomes in Type 1 Diabetes: Results from the DCCT/EDIC Studies

Cardiovascular (CV) complications are a major cause of morbimortality in long-standing type 1 diabetes (T1D) . Excessive weight gain has been associated with higher rates of CV events in the DCCT/EDIC studies. Moreover, fluctuation of body weight has emerged as an independent predictor of increased mortality and risk of CV outcomes, with evidence from the general population, from patients with coronary artery disease, and from patients with type 2 diabetes. We evaluated the association between weight fluctuation and CV events in patients with T1D from the DCCT/EDIC population. Body-weight fluctuation was measured by the average successive variability (ASV: average absolute difference between successive values) over the 9-year period of the DCCT. The primary outcome was a composite of major adverse CV events (MACE: nonfatal myocardial infarctions or cerebrovascular events, CV deaths) occurring during the first 15 years of EDIC follow-up. The risk of outcomes during follow-up was analyzed using adjusted Cox models according to tertiles of ASV. For the primary outcome, 1371 out of 1441 patients fulfilled the inclusion criteria for analysis [males: 52.41%, age: (37.53±6.82) years, mean HbA1c: (8.08±1.35) %, conventional/intensive treatment: 690/681 patients]. The cumulative incidence of MACE was 4.81%, 5.02%, and 6.58% for tertiles 1, 2, and 3, respectively (T1, T2, T3) (p=0.44) during (15.40±6.24) years of follow-up. Cox analysis adjusted for baseline EDIC characteristics (age, sex, treatment group) and time-dependent variables during DCCT (average BMI, CV risk factors, nephropathy) showed a hazard ratio (HR) for MACE of 1. (95% CI 0.58-1.92; p=0.85) for T2 and 1.34 (0.74-2.41; p=0.34) for T3, both compared to T1. For every increase of 1 standard deviation of ASV, the HR for MACE was 1. (0.86-1.42; p=0.44) . Despite a trend for a positive association, body-weight fluctuation was not significantly associated with an increased risk of MACE in patients with T1D. Disclosure I.Petria: None. S.Albuquerque: None. G.Varoquaux: None. J.Vie: None. G.Velho: None. G.Perseghin: Advisory Panel; AstraZeneca, Lilly, Merck Sharp &amp; Dohme Corp., Novo Nordisk, PIKDARE S.p.A., Sanofi. R.Roussel: None. L.Potier: Board Member; Boehringer Ingelheim International GmbH, Lilly, Novo Nordisk, Consultant; AstraZeneca, Sanofi.

Early and ongoing stable glycaemic control is associated with a reduction in major adverse cardiovascular events in people with type 2 diabetes: A primary care cohort study.

AimTo determine whether achieving early glycaemic control, and any subsequent glycaemic variability, was associated with any change in the risk of major adverse cardiovascular events (MACE).Materials and MethodsA retrospective cohort analysis from the Oxford‐Royal College of General Practitioners Research and Surveillance Centre database—a large, English primary care network—was conducted. We followed newly diagnosed patients with type 2 diabetes, on or after 1 January 2005, aged 25 years or older at diagnosis, with HbA1c measurements at both diagnosis and after 1 year, plus five or more measurements of HbA1c thereafter. Three glycaemic bands were created: groups A (HbA1c < 58 mmol/mol [<7.5%]), B (HbA1c ≥ 58 to 75 mmol/mol [7.5%‐9.0%]) and C (HbA1c ≥ 75 mmol/mol [≥9.0%]). Movement between bands was determined from diagnosis to 1 year. Additionally, for data after the first 12 months, a glycaemic variability score was calculated from the number of successive HbA1c readings differing by 0.5% or higher (≥5.5 mmol/mol). Risk of MACE from 1 year postdiagnosis was assessed using time‐varying Cox proportional hazards models, which included the first‐year transition and the glycaemic variability score.ResultsFrom 26 180 patients, there were 2300 MACE. Compared with group A‐>A transition over 1 year, those with C‐>A transition had a reduced risk of MACE (HR 0.75; 95% CI 0.60‐0.94; P = .014), whereas group C‐>C had HR 1.21 (0.81‐1.81; P = .34). Compared with the lowest glycaemic variability score, the greatest variability increased the risk of MACE (HR 1.51; 1.11‐2.06; P = .0096).ConclusionEarly control of HbA1c improved cardiovascular outcomes in type 2 diabetes, although subsequent glycaemic variability had a negative effect on an individual's risk.

Albuminuria screening in children with type 1 diabetes prior to and during the COVID-19 pandemic.

BackgroundAlbuminuria is an important risk factor for adverse renal and cardiovascular outcomes in type 1 diabetes (T1D). We sought to describe: (1) adherence to albuminuria screening prior to and during the COVID-19 pandemic and (2) occurrence of abnormal urine albumin-creatinine ratio (ACR) tests in children with T1D.MethodsThis cohort study involved children aged 18 years or younger with T1D followed in the diabetes clinic at a pediatric tertiary center. Data was collected from 2016 to 2020. Adherence was defined by Diabetes Canada (DC) Guidelines for T1D in Children and Adolescents (2018).ResultsOf the 165 children who met DC criteria for screening; 88 (32%) were male and the median age at diagnosis was 5.8 years. Twenty-eight (17%) children had not completed a single ACR test, and 30 (18%) completed all eligible ACR tests. Test completion decreased from 66% in 2019 to 45% in 2020. Of the 345 ACR tests completed, 40 (11%) were abnormal (>2.5 mg/mmol) and 29 abnormal ACR tests (72%) were not repeated.ConclusionAdherence to albuminuria screening in this pediatric diabetes clinic is suboptimal with deterioration during the COVID-19 pandemic. Patient/physician and program-level strategies to improve adherence will play an important role in quality improvement.Impact Albuminuria screening is an important part of pediatric diabetes care.In our study, pediatric albuminuria screening adherence was suboptimal at 66% in 2019 and deteriorated during the pandemic to 45% in 2020.Program and patient-level adherence to clinical guidelines and barriers to accessing diabetes care during the pandemic merit further study.

Meta-Analysis of the Efficacy and Safety of Finerenone in Diabetic Kidney Disease

Background: The phase III clinical trial of the nonsteroidal mineralocorticoid receptor antagonist finerenone (BAY 94-8862) has been completed, aiming to investigate renal and cardiovascular outcomes in type 2 diabetes (T2D) with chronic kidney disease (CKD). However, the efficacy and safety of finerenone in renal function remain controversial. The purpose of this study was to explore the efficacy and safety of finerenone in treating the patients with diabetic kidney disease (DKD). Methods: Databases of PubMed, Cochrane Library, Embase, and Web of Science were searched for randomized controlled trials (RCTs) on patients with DKD receiving finerenone treatment from inception to September 2021. Data including patient characteristics and interested outcomes were extracted, and the dichotomous data and continuous variables were evaluated using risk ratio (RR) with 95% confidence intervals (CIs) and mean differences (MD) with 95% CIs, respectively. Results: A total of 4 RCTs involving 13,945 patients were included in this meta-analysis. Analysis results demonstrated that patients receiving finerenone showed a significant decrease in changing urinary albumin-to-creatinine ratio (UACR) from baseline (MD: −0.30; 95% CI [−0.33, −0.27], p = 0.46, I² = 0%) (p < 0.05). The number of patients with ≥40% reduction in estimated glomerular filtration rate (eGFR) from baseline in the finerenone group was significantly smaller than that in the placebo group (RR: 0.85; 95% CI [0.78, 0.93], p = 0.60, I² = 0%) (p < 0.05). No difference was found in adverse events between the finerenone and placebo groups (RR: 1.00; 95% CI [0.98, 1.01], p = 0.94, I² = 0%) (p = 0.65). The incidence of hyperkalemia was higher in the finerenone group than that in the placebo group (RR: 2.03; 95% CI [1.83, 2.26], p = 0.95, I² = 0%) (p < 0.05). Conclusion: Finerenone contributes to the reduction of UACR and can ameliorate the deterioration of renal function in patients with T2D and CKD. The higher risk of hyperkalemia was found in the finerenone group compared with placebo; however, there was no difference in the risk of overall adverse events.

Subcutaneous infusion of exenatide and cardiovascular outcomes in type 2 diabetes: a non-inferiority randomized controlled trial.

Glucagon-like peptide 1 receptor agonists (GLP-1RAs) injected periodically have been shown to not increase and, for some members of this class, decrease the risk of cardiovascular events. The cardiovascular safety of delivering a continuous subcutaneous infusion of the GLP-1RA exenatide (ITCA 650) is unknown. Here, we randomly assigned patients with type 2 diabetes with, or at risk for, atherosclerotic cardiovascular disease (ASCVD) to receive ITCA 650 or placebo to assess cardiovascular safety in a pre-approval trial ( NCT01455896 ). The primary outcome was a composite of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke or hospitalization for unstable angina. On the basis of 2008 guidance from the US Food and Drug Administration, a non-inferiority margin of 1.8 for the upper bound of the 95% confidence interval (CI) of the hazard ratio (HR) was used. We randomized 4,156 patients (2,075 assigned to receive ITCA 650 and 2,081 assigned to receive placebo) who were followed for a median of 16 months. The primary outcome occurred in 4.6% (95/2,075) of patients in the ITCA 650 group and 3.8% (79/2,081) of patients in the placebo group, meeting the pre-specified non-inferiority criterion (HR = 1.21, 95% CI, 0.90-1.63, Pnon-inferiority = 0.004). Serious adverse events were similar between the two groups. Adverse events were more frequent in the ITCA 650 group (72%, 1,491/2,074) than in the placebo group (63.9%, 1,325/2,070), mainly due to an increase in gastrointestinal events and disorders while on ITCA 650. In patients with type 2 diabetes with, or at risk for, ASCVD, ITCA 650 was non-inferior to placebo. A larger and longer-duration cardiovascular outcomes trial is needed to define more precisely the cardiovascular effects of ITCA 650 in this population.

Abstract 10401: Uptake and Predictors of SGLT2i in Patients with Type 2 Diabetes and Cardiovascular Disease

Introduction: While sodium glucose cotransporter 2 inhibitors (SGLT2i) improve cardiovascular outcomes in type 2 diabetes (T2D) and cardiovascular disease (CVD), their uptake in clinical practice in this population is unclear. Therefore, we evaluated trends in SGLT2i use and identified predictors of use in patients with concomitant T2D and CVD. Methods: We conducted an observational study using population-based health data in Ontario, Canada from 4/2016-3/2020 of patients ≥65 years old with a first diagnosis of T2D plus CVD. In each yearly cohort, we estimated the prevalent use of SGLT2i (≥1 prescription) within 1 year, including by demographic and comorbidity subgroups. In the overall cohort, we used multivariable logistic regression models to identify factors associated with SGLT2i use. Results: We identified 208,303 patients with T2D and CVD [median age 74.0 years (IQR 68.0-80.0); 63.5% male]. The proportion of patients dispensed an SGLT2i increased over time, from 7.0% in 2016 to 20.1% in 2019. In 2019, use in those ≥75 years was 50% lower than those &lt;75 years (12.9% vs. 28.3%;p&lt;.0001), and use in those without chronic kidney disease (CKD) was 50% higher than those with CKD (22.0% vs. 15.0%;p&lt;.0001); although SGLT2i use increased in all groups over time. Independent factors associated with increased odds of SGLT2i use were HbA1c ≥8 vs. &lt;7 (OR 3.33, 95%CI:3.22-3.46), use of 2+ non-insulin antihyperglycemic agents (OR 2.63, 95%CI:2.56-2.71), and an endocrinologist visit in prior year (OR 1.50, 95%CI:1.45-1.55). Those &gt;75 years (OR 0.39, 95%CI:0.38-0.40), with high frailty score (OR 0.38, 95%CI:0.35-0.42), or serum creatinine 1.4-2mg/dL vs. &lt;1.4 (OR 0.55, 95%CI:0.52-0.57) were less likely to use SGLT2i. Conclusions: In a real-world population of T2D and CVD, only 1 in 5 patients used an SGLT2i, although use increased over time. Markers of worse diabetes control were associated with increased SGLT2i use, while markers of more comorbidity were associated with less use.