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

Saving time by replacing the standardised two-hour oral glucose tolerance test with a one-hour test : validation of a new screening algorithm in patients with coronary artery disease from the ESC-EORP EUROASPIRE V registry

Aims: An oral glucose tolerance test (OGTT) combining fasting (FPG) and 2-hour plasma glucose (2hPG) is the most sensitive method for detecting type 2 diabetes (T2DM). Since it is considered time-consuming, we aim at validating a previously proposed screening algorithm based on a 1-hour plasma glucose (1hPG) with a 12 mmol/L threshold. Methods: Nine-hundred-eighteen patients with coronary artery disease (CAD) without known T2DM from the EUROASPIRE V cross-sectional survey underwent an OGTT. The reference for T2DM was 2hPG > 11.1 mmol/L. T2DM diagnosis by HbA1c > 6.5%(48 mmol/mol), FPG > 7.0 mmol/L, and 1hPG > 12 mmol/L were compared with the outcome of 2hPG. Results: Mean FPG, HbA1c and 2hPG were 6.1 mmol/L, 5.6%(38 mmol/mol) and 7.8 mmol/L respectively. Ninety-six patients (10%) were diagnosed with T2DM according to 2hPG. Using this definition, in the group with FPG 8.0 mmol/L and 1hPG > 15.0 mmol/L were identified as having T2DM. According to the algorithm, in 79% of patients T2DM could be excluded by combining FPG < 6.5 mmol/L and 1hPG < 12 mmol/L. Conclusions: T2DM Screening by means of an algorithm combining FPG and 1hPG limits the demand of a 2hOGTT in 79% of CAD patients without known T2DM. HbA1c did not add to the information derived from this algorithm. (c) 2021 Published by Elsevier B.V

The haemoglobin glycation index as predictor of diabetes-related complications in the AleCardio trial

The haemoglobin glycation index (HGI) quantifies the interindividual variation in the propensity for glycation and is a predictor of diabetes complications and adverse effects of intensive glucose lowering. We investigated the relevance of HGI as independent predictor of complications by using data of the AleCardio trial. The AleCardio trial randomized 7226 type 2 diabetes patients with an acute coronary syndrome to aleglitazar or placebo. From 6458 patients with baseline glycated haemoglobin (HbA(1c)) and fasting plasma glucose (FPG), a linear regression equation, HbA(1c) (%)=5.45+0.0158 * FPG (mg/dl), was used to calculate predicted HbA(1c) and derive HGI (= observed - predicted HbA(1c)). With multivariate Cox regression we examined the association with major adverse cardiac events, cardiovascular mortality, total mortality and hypoglycaemia, irrespective of treatment allocation, using HGI subgroups (low, intermediate and high) and HGI as continuous variable. Patients with high HGI were younger, more often non-Caucasian, had a longer duration of diabetes, showed more retinopathy and used insulin more often. Hypoglycaemia occurred less often in the low HGI subgroup, but this difference disappeared after adjustment for duration of diabetes, insulin and sulphonylurea use. Low HGI patients were at lower risk for cardiovascular mortality (hazard ratio 0.64; 95% confidence interval 0.44-0.93, p=0.020) and total mortality (hazard ratio 0.69; 95% confidence interval 0.50-0.95, p = 0.025), as compared with high HGI patients. Every percentage increase in HGI was associated with a 16% increase in the risk for cardiovascular mortality (p=0.005). The association between HGI and mortality disappeared with additional adjustment for HbA(1c). HGI predicts mortality in diabetes patients with acute coronary syndromes, but no better than HbA(1c

Post-Discharge Worsening Renal Function in Patients with Type 2 Diabetes and Recent Acute Coronary Syndrome

BACKGROUND: Worsening renal function during hospitalization for an acute coronary syndrome is strongly predictive of in-hospital and long-term outcome. However, the role of post-discharge worsening renal function has never been investigated in this setting. METHODS: We considered the placebo cohort of the AleCardio trial comparing aleglitazar with standard medical therapy among patients with type 2 diabetes mellitus and a recent acute coronary syndrome. Patients who had died or had been admitted to hospital for heart failure before the 6-month follow-up, as well as patients without complete renal function data, were excluded, leaving 2776 patients for the analysis. Worsening renal function was defined as a >20% reduction in estimated glomerular filtration rate from discharge to 6 months, or progression to macroalbuminuria. The Cox regression analysis was used to determine the prognostic impact of 6-month renal deterioration on the composite of all-cause death and hospitalization for heart failure. RESULTS: Worsening renal function occurred in 204 patients (7.34%). At a median follow-up of 2 years the estimated rates of death and hospitalization for heart failure per 100 person-years were 3.45 (95% confidence interval [CI], 2.46-6.36) for those with worsening renal function, versus 1.43 (95% CI, 1.14-1.79) for patients with stable renal function. At the adjusted analysis worsening renal function was associated with the composite endpoint (hazard ratio 2.65; 95% CI, 1.57-4.49; P <.001). CONCLUSIONS: Post-discharge worsening renal function is not infrequent among patients with type 2 diabetes and acute coronary syndromes with normal or mildly depressed renal function, and is a strong predictor of adverse cardiovascular events