Effect of semaglutide on major adverse cardiovascular events by baseline kidney parameters in participants with type 2 diabetes and at high risk of cardiovascular disease:SUSTAIN 6 and PIONEER 6 post hoc pooled analysis

Background: Semaglutide is a glucose-lowering treatment for type 2 diabetes (T2D) with demonstrated cardiovascular benefits; semaglutide may also have kidney-protective effects. This post hoc analysis investigated the association between major adverse cardiovascular events (MACE) and baseline kidney parameters and whether the effect of semaglutide on MACE risk was impacted by baseline kidney parameters in people with T2D at high cardiovascular risk.Methods: Participants from the SUSTAIN 6 and PIONEER 6 trials, receiving semaglutide or placebo, were categorised according to baseline kidney function (estimated glomerular filtration rate [eGFR] &lt; 45 and ≥ 45–&lt;60 versus ≥ 60 mL/min/1.73 m2) or damage (urine albumin:creatinine ratio [UACR] ≥ 30–≤300 and &gt; 300 versus &lt; 30 mg/g). Relative risk of first MACE by baseline kidney parameters was evaluated using a Cox proportional hazards model. The same model, adjusted with inverse probability weighting, and a quadratic spline regression were applied to evaluate the effect of semaglutide on risk and event rate of first MACE across subgroups. The semaglutide effects on glycated haemoglobin (HbA1c), body weight (BW) and serious adverse events (SAEs) across subgroups were also evaluated.Results: Independently of treatment, participants with reduced kidney function (eGFR ≥ 45–&lt;60 and &lt; 45 mL/min/1.73 m2: hazard ratio [95% confidence interval]; 1.36 [1.04;1.76] and 1.52 [1.15;1.99]) and increased albuminuria (UACR ≥ 30–≤300 and &gt; 300 mg/g: 1.53 [1.14;2.04] and 2.52 [1.84;3.42]) had an increased MACE risk versus those without. Semaglutide consistently reduced MACE risk versus placebo across all eGFR and UACR subgroups (interaction p value [pINT] &gt; 0.05). Semaglutide reduced HbA1c regardless of baseline eGFR and UACR (pINT&gt;0.05); reductions in BW were affected by baseline eGFR (pINT&lt;0.001) but not UACR (pINT&gt;0.05). More participants in the lower eGFR or higher UACR subgroups experienced SAEs versus participants in reference groups; the number of SAEs was similar between semaglutide and placebo arms in each subgroup.Conclusions: MACE risk was greater for participants with kidney impairment or damage than for those without. Semaglutide consistently reduced MACE risk across eGFR and UACR subgroups, indicating that semaglutide provides cardiovascular benefits in people with T2D and at high cardiovascular risk across a broad spectrum of kidney function and damage.Trial registrations: NCT01720446; NCT02692716.</p

Semaglutide and cardiovascular outcomes by baseline HbA1c in diabetes: the SUSTAIN 6 and PIONEER 6 trials.

No abstract available

Eligibility for dapagliflozin and empagliflozin in a real-world heart failure population

Background: We investigated eligibility for dapagliflozin and empagliflozin in a real-world heart failure (HF) cohort based on selection criteria of DAPA-HF, DELIVER, and EMPEROR trials. Methods and Results: Selection criteria were applied to the Swedish HF registry out-patient population according to three scenarios: (i) a “trial scenario” applying all selection criteria; (ii) a “pragmatic scenario” applying the most clinically relevant criteria; (iii) a “label scenario” following the regulatory agencies labels. Of 49,317 patients, 55% had ejection fraction (EF)&lt;40% and were assessed for eligibility based on DAPA-HF and EMPEROR-Reduced, 45% had EF≥40% and were assessed based on EMPEROR-Preserved and DELIVER. Eligibility using trial, pragmatic and label scenarios was: 35%, 61% and 80% for DAPA-HF; 31%, 55% and 81% for EMPEROR-Reduced; 30%, 61% and 74% for DELIVER; 32%, 59% and 75% for EMPEROR-Preserved. Main selection criteria limiting eligibility were HF duration and NT-proBNP. Eligible patients had more severe HF, more comorbidities, higher use of HF treatments and higher mortality/morbidity. Conclusions: In a real-world HF setting, eligibility for SGLT2i was similar whether selection criteria from DAPA-HF or EMPEROR-Reduced were applied in HFrEF, or EMPEROR-Preserved or DELIVER in HFpEF. These data might help stakeholders assessing the consequences of future trial eligibility

Highlights from 2022 in EHJ Open.

editorial reviewe

Patients with coronary artery disease and diabetes need improved management: a report from the EUROASPIRE IV survey: a registry from the EuroObservational Research Programme of the European Society of Cardiology

BACKGROUND: In order to influence every day clinical practice professional organisations issue management guidelines. Cross-sectional surveys are used to evaluate the implementation of such guidelines. The present survey investigated screening for glucose perturbations in people with coronary artery disease and compared patients with known and newly detected type 2 diabetes with those without diabetes in terms of their life-style and pharmacological risk factor management in relation to contemporary European guidelines. ----- METHODS: A total of 6187 patients (18-80 years) with coronary artery disease and known glycaemic status based on a self reported history of diabetes (previously known diabetes) or the results of an oral glucose tolerance test and HbA1c (no diabetes or newly diagnosed diabetes) were investigated in EUROASPIRE IV including patients in 24 European countries 2012-2013. The patients were interviewed and investigated in order to enable a comparison between their actual risk factor control with that recommended in current European management guidelines and the outcome in previously conducted surveys. ----- RESULTS: A total of 2846 (46%) patients had no diabetes, 1158 (19%) newly diagnosed diabetes and 2183 (35%) previously known diabetes. The combined use of all four cardioprotective drugs in these groups was 53, 55 and 60%, respectively. A blood pressure target of 9.0% (>75 mmol/mol). Of the patients with diabetes 69% reported on low physical activity. The proportion of patients participating in cardiac rehabilitation programmes was low (≈40 %) and only 27% of those with diabetes had attended diabetes schools. Compared with data from previous surveys the use of cardioprotective drugs had increased and more patients were achieving the risk factor treatment targets. ----- CONCLUSIONS: Despite advances in patient management there is further potential to improve both the detection and management of patients with diabetes and coronary artery disease

Myocardial infarction and diabetes mellitus : Studies on glucose lowering therapies and novel risk markers based on observations from the DIGAMI 2 trial

Background Patients with myocardial infarction (MI) and type 2 diabetes (T2DM) and have a poor prognosis. Hyperglycemia is an independent risk predictor. The best tools for glucose control are debated. Important is identification of biomarkers to gain further pathophysiological insights and new therapeutic possibilities. Aims In patients with acute MI and T2DM 1. Explore the prognostic impact of hypoglycemia during hospitalization for MI 2. Study the prognostic impact of glucose lowering treatment 3. Investigate the relation between Copeptin and IGFBP-1 and their prognostic impact 4. Characterize MBL geno- and phenotypes and to investigate their prognostic importance Study population This thesis is based on epidemiological reports from the DIGAMI 2 trial comprising 1253 patients with T2DM and acute MI. DIGAMI 2 was a randomized trial with the primary aim to compare three glucose lowering strategies testing the hypothesis that insulin-based metabolic control reduces mortality. Hypoglycemia during hospitalization for acute MI Hypoglycemic episodes were recorded in 153 patients (symptomatic = 45). Patients with hypoglycemia were older, had a longer duration of T2DM, a lower body weight and more often a history of heart failure. The mortality and cardiovascular morbidity did not differ between patients with or without hypoglycemia besides that patients who were symptomatic were at increased risk of death. This higher risk disappeared after adjustment for confounding factors. Glucose lowering treatment and prognosis During the initial follow-up of 2.3 years the adjusted hazard ratio (HR) for non-fatal MI and stroke, in patients discharged alive (n=1181), was 1.73 (95% CI 1.26 2.37; p =0.0007) with insulin treatment, 0.81 (95% CI 0.57 1.14; p = 0.23) with sulphonylureas and 0.63 (95% CI 0.42 0.95; p = 0.03) with metformin. None of the glucose lowering treatments influenced mortality. The odds ratio for insulin on non-fatal cardiovascular events was 1.90 (95% CI 1.38-2.63; p=<0.0001) without influencing mortality after an extended follow-up period of 4.1 years. Metformin was associated with a lower mortality and a lower risk of death of malignancies. There were no difference in total or cardiovascular mortality between the randomized treatment groups but the risk of dying of malignancies was highest in patients randomized to long-term insulin. Novel risk markers and prognosis Copeptin, a surrogate marker for vasopressin, was associated with IGFBP-1 (r = 0.53; p<0.001) in 393 patients participating in the biochemical program of DIGAMI 2. Both biomarkers were predictors of events (cardiovascular death, MI and stroke) in univariate analyses. In the final statistical model, adjusting for age and renal function, copeptin was the only independent predictor (HR 1.35; 95% CI: 1.16-1.57; p<0.001). Serum (S)-MBL, an activator of the complement system, was determined in 387 and MBL genotypes in 287 patients. Fifty four percent had high coding (median S-MBL=2658 ìg/l; IQR 1715 3829) and 46% low coding MBL genotype (median S-MBL=373ìg/l; IQR 100-765). S-MBL did not predict events. The risk of events was lower in patients with high genotype and S-MBL above median for their genotype (HR 0.49; 95%CI 0.26-0.92; p= 0.026) than among patients with low genotype and S-MBL below median for their genotype. This relation did, however, only reach borderline significance in adjusted analyses. Conclusions Hypoglycemia during hospitalization is not an independent risk factor for mortality and cardiovascular morbidity in patients with T2DM and MI. It is more prevalent in patient at high risk for other reasons. Glucose lowering agents seem to impact cardiovascular morbidity, mortality and deaths from malignancies, a finding that deserves further evaluation. Copeptin may explain at least some of the prognostic impact ofIGFBP-1 in these patients an observation that may open for new therapeutic attempts. MBL did not have a significant impact on prognosis

Pay for disease or invest in health?

To access publisher full text version of this article. Please click on the hyperlink in Additional Links field.Hjärt–kärlsjukdom är den ledande enskilda orsaken till död och ohälsa i vår del av världen. Den medicinska och ekonomiska bördan av dessa sjukdomar är enorm. Även om nyinsjuknandet och dödligheten i tex hjärtinfarkt har minskat i vårt land, liksom i många europeiska länder, är antalet människor som insjuknar i förtid och som lever med resttillstånd efter olika hjärt–kärlsjukdomar snarast i stigande, vilket sammanhänger med att vi lever längre och att överlevnaden efter hjärtinfarkt och slaganfall har ökat. Största delen av dessa sjukdomar liksom av andra kroniska, icke-smittsamma sjukdomar (cancer, lungsjukdom, diabetes osv) sammanhänger med påverkbara, livsstilsrelaterade riskfaktorer. Hälsosamma val, dvs bra mat, fysisk aktivitet, frånvaro av tobaksbruk och undvikande av överkonsumtion av alkohol, kan förhindra eller i vart fall fördröja ett insjuknande. Den medicinska professionen bör ta som sin uppgift att i samverkan med politiker, hälsovårdsadministratörer och medier upplysa allmänheten om dessa enkla fakta. Genom kloka policybeslut kan man underlätta för befolkningen att göra hälsosamma val redan från de tidiga barnaåren och genom hela livscykeln

Will oral semaglutide be a game-changer in the management of type 2 diabetes in primary care?

GLP-1 receptor agonists (GLP-1RAs) are recommended for patients with type 2 diabetes (T2D), particularly those at high cardiovascular risk. Oral semaglutide is the first oral GLP-1RA. In clinical trials, oral semaglutide 14 mg reduced mean HbA1c by approximately 1.1–1.5% and reduced body weight by up to 5 kg. These changes were significantly greater compared with empagliflozin, sitagliptin and liraglutide (p < 0.05 for estimated treatment differences at 52 weeks in patients on treatment without rescue medication use). The most common side effects were gastrointestinal, mainly mild-to-moderate and transient nausea. Oral semaglutide may change the paradigm of T2D treatment in primary care

Copeptin is associated with mortality in elderly people

© 2021 The Authors. European Journal of Clinical Investigation published by John Wiley & Sons Ltd on behalf of Stichting European Society for Clinical Investigation Journal Foundation.BACKGROUND: Elevated copeptin, a marker for vasopressin release, has been associated with impaired prognosis in acute myocardial infarction (MI). The aim was to investigate whether this association extends beyond the acute phase and whether it is related to markers of stress (cortisol) and heart failure (NTproBNP). METHODS: Copeptin, cortisol and NTproBNP were measured in 926 participants (age: 76.0; male: 48.5%) in the ICELAND MI study whereof 246 had a previous MI (91 recognizable (RMI) and 155 previously unrecognizable (UMI) detected by cardiac magnetic resonance imaging). The primary endpoint was cardiovascular events (CVEs), and secondary endpoints were total mortality, heart failure and MI (median follow-up was 9.1 years). The relation between copeptin and prognosis was assessed with the Cox proportional hazard regression (unadjusted, adjusted for cortisol and NTproBNP, respectively, and a multiple model: copeptin, cortisol, NTproBNP, age, sex, serum creatinine, heart failure). RESULTS: Copeptin was higher in participants with MI (8.9 vs. 6.4 pmol/L; P < .01), with no difference between RMI vs. UMI. Increased copeptin correlated with evening cortisol (r = .11; P < .01) and NTproBNP (r = .07; P = .04). Copeptin was associated with CVE and total mortality after adjusting for cortisol and NTproBNP separately, and remained significantly associated with total mortality in the multiple model. CONCLUSIONS: Copeptin was higher in subjects with previous MI regardless whether previously recognized or not. Copeptin correlated weakly with cortisol and NTproBNP, and was independently associated with total mortality. This indicates that the prognostic implications of copeptin are not only mediated by heart failure or stress, supporting the assumption that copeptin is a marker of general vulnerability.Peer reviewe

Risk and management of pre-diabetes

Type 2 diabetes mellitus (T2DM) is associated with a two- to four-fold increased risk of developing cardiovascular disease (CVD) and microvascular complications, which may already be present before diagnosis. It is, therefore, important to detect people with an increased risk of T2DM at an early stage. In order to identify individuals with so-called ‘pre-diabetes’, comprising impaired fasting glucose (IFG) and impaired glucose tolerance (IGT), current guidelines have developed definitions based on fasting plasma glucose, two-hour glucose concentrations and haemoglobin A1c. Subjects with pre-diabetes are at an increased risk of developing T2DM and CVD. This elevated risk seems similar according to the different criteria used to define pre-diabetes. The risk of progression to T2DM or CVD does, however, depend on other risk factors such as sex, body mass index and ethnicity. Based on the risk factors to develop T2DM, many risk assessment models have been developed to identify those at highest risk. These models perform well to identify those at risk and could be used to initiate preventive interventions. Many studies have shown that lifestyle modification and metformin are effective in preventing the development of T2DM, although lifestyle modification seems to have a more sustainable effect. In addition, lifestyle modification seems more effective in those with IGT than those with IFG. In this review, we will describe the different definitions used to define pre-diabetes, progression from pre-diabetes to T2DM or other vascular complications, risk factors associated with progressions and the management of progression to T2DM, ending with clinical recommendations