Cancer risks of anti-hyperglycemic drugs for type 2 diabetes treatment - a clinical appraisal

AIM: A clinical appraisal of existing scientific literature sought to assess the need for long-term prospective epidemiological studies to investigate an increased cancer risk of anti-hyperglycemic medication in type 2 diabetes. METHOD: A focus statement was formulated as: "With a higher risk of cancers in patients with type 2 diabetes, all anti-hyperglycemic drugs should undergo long-term, prospective epidemiological studies for cancer risks." Field surveys were sent to practicing physicians and endocrinologists to identify the currently prevalent level of acceptance of this statement. Subsequently, a meeting with a six-member panel of key opinion leaders was held to discuss published evidence in support and against the statement. This publication reviews the publications and discussion points brought forth in this meeting and their effect on statement acceptance by the panel. RESULTS: Whereas the majority of field survey responders primarily agreed with the statement, panel members were divided in their statement support. This division remained intact after review of the literature. CONCLUSIONS: While there was evidence that type 2 diabetes is associated with an increased risk of cancer, existing studies seemed insufficient to definitively demonstrate a link between cancer risk and use of specific anti-hyperglycemic therapies

Uric acid and the cardio-renal effects of SGLT2 inhibitors

Sodium/glucose co‐transporter‐2 (SGLT2) inhibitors, which lower blood glucose by increasing renal glucose elimination have been shown to reduce the risk of adverse cardiovascular (CV) and renal events in type 2 diabetes. This has been ascribed in part to haemodynamic changes, body weight reduction and several possible effects on myocardial, endothelial and tubulo‐glomerular functions as well as reduced glucotoxicity. This review evaluates evidence that an effect of SGLT2 inhibitors to lower uric acid may also contribute to reduced cardio‐renal risk. Chronically raised circulating uric acid concentrations are associated with increased risk of hypertension, CV disease and chronic kidney disease (CKD). The extent to which uric acid contributes to these conditions either as a cause or aggravating factor remains unclear, but interventions that reduce urate production or increase urate excretion in hyperuricaemic patients have consistently improved cardio‐renal prognoses. Uric acid concentrations are often raised in type 2 diabetes, contributing to the ‘metabolic syndrome’ of CV risk. Treating type 2 diabetes with an SGLT2 inhibitor increases uric acid excretion, reduces circulating uric acid and improves parameters of CV and renal function. This raises the possibility that the lowering of uric acid by SGLT2 inhibition may assist in reducing adverse CV events and slowing progression of CKD in type 2 diabetes. SGLT2 inhibition might also be useful in the treatment of gout and gouty arthritis, especially when co‐existent with diabetes

Impact of Cardio-Renal-Metabolic Comorbidities on Cardiovascular Outcomes and Mortality in Type 2 Diabetes Mellitus

BACKGROUND: We evaluated the incremental contribution of chronic kidney disease (CKD) to the risk of major adverse cardiovascular (CV) events (MACE), heart failure (HF), and all-cause mortality (ACM) in type 2 diabetes mellitus (T2DM) patients and its importance relative to the presence of other cardio-renal-metabolic (CaReMe) comorbidities. METHODS: Patients (≥40 years) were identified at the time of T2DM diagnosis from US (Humedica/Optum) and UK (Clinical Practice Research Datalink) databases. Patients were monitored post-diagnosis for modified MACE (myocardial infarction, stroke, ACM), HF, and ACM. Adjusted hazard ratios were obtained using Cox proportional-hazards regression to evaluate the relative risk of modified MACE, HF, and ACM due to CKD. Patients were stratified by the presence or absence of atherosclerotic CV disease (ASCVD) and age. RESULTS: Between 2011 and 2015, of 227,224 patients identified with incident T2DM, 40,063 (17.64%) had CKD. Regardless of prior ASCVD, CKD was associated with higher risk of modified MACE, HF, and ACM; this excess hazard was more pronounced in older patients with prior ASCVD. In time-to-event analyses in the overall cohort, patients with T2DM + CKD or T2DM + CKD + hypertension + hyperlipidemia had increased risks for modified MACE, HF, and ACM versus patients with T2DM and no CaReMe comorbidities. Patients with CKD had higher risks for and shorter times to modified MACE, HF, and ACM than those without CKD. CONCLUSION: In T2DM patients, CKD presence was associated with higher risk of modified MACE, HF, and ACM. This may have risk-stratification implications for T2DM patients based on background CKD and highlights the potential importance of novel renoprotective strategies

Report from the CVOT Summit 2020: new cardiovascular and renal outcomes

The 6th Cardiovascular Outcome Trial (CVOT) Summit “Cardiovascular and Renal Outcomes 2020” was the first to be held virtually on October 29–30, 2020. As in previous years, this summit served as reference meeting for in-depth discussions on the topic of recently completed and presented major outcome trials. This year, focus was placed on the outcomes of VERTIS-CV, EMPEROR-Reduced, DAPA-CKD, and FIDELIO-DKD. Trial implications for diabetes management and the impact on new treatment algorithms were highlighted for diabetologists, cardiologists, endocrinologists, nephrologists, and general practitioners. Discussion evolved from major outcome trials using SGLT-2 inhibitors for treatment and prevention of heart failure and chronic kidney disease in people with and without diabetes, to additional therapy options for chronic kidney disease with a novel mineralocorticoid receptor antagonist. Furthermore, challenges in diabetes management like COVID-19 and obesity, as well as novel treatment strategies and guidelines, were discussed. The 7th Cardiovascular Outcome Trial Summit will be held virtually on November, 18–19, 2021 (http://www.cvot.org)

Trends in the Prevalence of Acute Kidney Injury in Patients with Acute Myocardial Infarction

Comparative Medicine - OneHealth and Comparative Medicine Poster SessionIntroduction: Acute kidney injury (AKI) is common in patients (pts) with acute myocardial infarction (AMI), and associated with permanent renal impairment and death. While guidelines increasingly emphasize the importance of AKI prevention, whether the rates of AKI changed over time is unknown. Methods: We studied 35,425 pts hospitalized with AMI in 66 U.S. centers from 2000-08 using Health Facts, a national database with detailed information on in-hospital renal function. AKI was defined as absolute creatinine increase of ≥ 0.3 mg/dL or relative increase of ≥50%. Temporal trends in AKI during the 9-year study period were evaluated using hierarchical logistic regression, adjusting for secular changes in baseline creatinine and other known AKI predictors. Results: From 2000-08, mean age increased (66.9 vs 68.8 yrs), as did baseline creatinine (1.4 vs 1.5 mg/dL), rate of cardiogenic shock (5.1 vs 6.3%), diabetes (30.4 vs 35.8%), coronary angiography (57 vs 68%), and PCI (30.2 vs 45.2%, P<0.001 for all comparisons). Despite increase in AKI risk factors, the rates of AKI declined steadily (Figure). The trend of decreasing AKI rates persisted after multivariable adjustment (P=0.01). Conclusions: While AKI still affects nearly 1 in 4 AMI pts, the rates of AKI declined significantly from 2000-08, despite the aging population and rising prevalence of AKI risk factors. These findings may reflect the impact of increased clinician awareness, better risk stratification, and AKI prevention efforts during this time period

Hospital Variability in Use of Anticoagulant Strategies During Acute Myocardial Infarction Treated With an Early Invasive Strategy

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/139118/1/jah31000.pd

Effects of dapagliflozin on mortality in patients with chronic kidney disease: a pre-specified analysis from the DAPA-CKD randomized controlled trial

AIMS : Mortality rates from chronic kidney disease (CKD) have increased in the last decade. In this pre-specified analysis of the DAPA-CKD trial, we determined the effects of dapagliflozin on cardiovascular and non-cardiovascular causes of death. METHODS AND RESULTS : DAPA-CKD was an international, randomized, placebo-controlled trial with a median of 2.4 years of follow-up. Eligible participants were adult patients with CKD, defined as a urinary albumin-to-creatinine ratio (UACR) 200-5000 mg/g and an estimated glomerular filtration rate (eGFR) 25-75 mL/min/1.73 m2. All-cause mortality was a key secondary endpoint. Cardiovascular and non-cardiovascular death was adjudicated by an independent clinical events committee. The DAPA-CKD trial randomized participants to dapagliflozin 10 mg/day (n = 2152) or placebo (n = 2152). The mean age was 62 years, 33% were women, the mean eGFR was 43.1 mL/min/1.73 m2, and the median UACR was 949 mg/g. During follow-up, 247 (5.7%) patients died, of whom 91 (36.8%) died due to cardiovascular causes, 102 (41.3%) due to non-cardiovascular causes, and in 54 (21.9%) patients, the cause of death was undetermined. The relative risk reduction for all-cause mortality with dapagliflozin (31%, hazard ratio [HR] [95% confidence interval (CI)] 0.69 [0.53, 0.88]; P = 0.003) was consistent across pre-specified subgroups. The effect on all-cause mortality was driven largely by a 46% relative risk reduction of non-cardiovascular death (HR [95% CI] 0.54 [0.36, 0.82]). Deaths due to infections and malignancies were the most frequently occurring causes of non-cardiovascular deaths and were reduced with dapagliflozin vs. placebo. CONCLUSION : In patients with CKD, dapagliflozin prolonged survival irrespective of baseline patient characteristics. The benefits were driven largely by reductions in non-cardiovascular death

Methods and rationale of the DISCOVER CKD global observational study

Background: Real-world data for patients with chronic kidney disease (CKD), specifically pertaining to clinical management, metabolic control, treatment patterns, quality of life (QoL) and dietary patterns, are limited. Understanding these gaps using real-world, routine care data will improve our understanding of the challenges and consequences faced by patients with CKD, and will facilitate the long-term goal of improving their management and prognosis. Methods: DISCOVER CKD follows an enriched hybrid study design, with both retrospective and prospective patient cohorts, integrating primary and secondary data from patients with CKD from China, Italy, Japan, Sweden, the UK and the USA. Data will be prospectively captured over a 3-year period from >1000 patients with CKD who will be followed up for at least 1 year via electronic case report form entry during routine clinical visits and also via a mobile/tablet-based application, enabling the capture of patient-reported outcomes (PROs). In-depth interviews will be conducted in a subset of ∼100 patients. Separately, secondary data will be retrospectively captured from >2 000 000 patients with CKD, extracted from existing datasets and registries. Results: The DISCOVER CKD program captures and will report on patient demographics, biomarker and laboratory measurements, medical histories, clinical outcomes, healthcare resource utilization, medications, dietary patterns, physical activity and PROs (including QoL and qualitative interviews). Conclusions: The DISCOVER CKD program will provide contemporary real-world insight to inform clinical practice and improve our understanding of the epidemiology and clinical and economic burden of CKD, as well as determinants of clinical outcomes and PROs from a range of geographical regions in a real-world CKD setting