BackgroundEarly glucose lowering intervention in subjects with type 2 diabetes mellitus was demonstrated to be beneficial in terms of micro- and macrovascular risk reduction. However, most of currently ongoing cardiovascular outcome trials are performed in subjects with manifest atherosclerosis and long-standing diabetes. Therefore, the aim of this study is to investigate the effects of the dipeptidylpeptidase-4 inhibitor linagliptin in subjects with coronary artery disease (CAD) but early type 2 diabetes mellitus (T2DM) on a set of cardiovascular surrogate measurements.MethodsIn this randomized, placebo-controlled, double-blind, single-center study, we included subjects with early diabetes (postchallenge diabetes (2 h glucose > 200 mg/dl) or T2DM treated with diet only or on a stable dose of metformin monotherapy and an HbA1c < 75 mmol/mol) and established CAD. Participants were randomized to receive either linagliptin (5 mg) once daily orally or placebo for 12 weeks. The primary outcome was the change in flow mediated dilatation (FMD). The secondary objective was to investigate the effect of linagliptin treatment on arginine bioavailability ratios [Global arginine bioavailability ratio (GABR) and arginine to ornithine ratio (AOR)]. Arginine, ornithine and citrulline were measured in serum samples with a conventional usual amino acid analysis technique, involving separation of amino acids by ion exchange chromatography followed by postcolumn continuous reaction with ninhydrin. GABR was calculated by l-arginine divided by the sum of (l-ornithine plus l-citrulline). The AOR was calculated by dividing l-arginine by l-ornithine levels. Group comparisons were calculated by using a two-sample t-test with Satterthwaite adjustment for unequal variances.ResultsWe investigated 43 patients (21% female) with a mean age of 63.3 ± 8.2 years. FMD at baseline was 3.5 ± 3.1% in the linagliptin group vs. 4.0 ± 2.9% in the placebo group. The change in mean FMD in the linagliptin group was not significantly different compared to the change in the placebo group (0.43 ± 4.84% vs. − 0.45 ± 3.01%; p = 0.486). No significant improvements were seen in the arginine bioavailability ratios (GABR; p = 0.608 and AOR; p = 0.549).ConclusionLinagliptin treatment in subjects with CAD and early T2DM did not improve endothelial function or the arginine bioavailability ratios.Trial registration ClinicalTrials.gov, NCT02350478 (https://clinicaltrials.gov/ct2/show/NCT02350478)Electronic supplementary materialThe online version of this article (10.1186/s12933-018-0716-x) contains supplementary material, which is available to authorized users.
Background: Patients with type 2 diabetes (T2DM) are at increased risk for macrovascular events as well as for microvascular complications. There is evidence that in patients with coronary artery disease (CAD), about 35 % suffer from manifest T2DM. Early glucose-lowering intervention in subjects with T2DM has been demonstrated to be beneficial in terms of cardiovascular risk reduction. But thus far, no data are available regarding investigating the impact of linagliptin treatment in patients with early diabetes on cardiovascular endpoints or surrogate parameters. Therefore, the aim of this study is to investigate the effects of linagliptin in CAD patients with early T2DM on various cardiovascular surrogate measurements including mechanical and biochemical endothelial function assessments.
Background: Short-term effects of alirocumab on vascular function have hardly been investigated. Moreover, there is a scarce of reliable non-invasive methods to evaluate atherosclerotic changes of the vasculature. The ALIROCKS trial was performed to address these issues using standard ultrasound-based procedures and a completely novel magnetic resonance-based imaging technique. Methods: A total of 24 patients with an indication for treatment with PCSK9 antibodies were recruited. There were 2 visits to the study site, the first before initiation of treatment with alirocumab and the second after 10 weeks of treatment. The key outcome measures included the change of carotid vessel wall fractional anisotropy, a novel magnetic resonance-based measure of vascular integrity, and the changes of carotid intima-media thickness and flow-dependent dilatation of the brachial artery measured with ultrasound. Results: A total of 19 patients completed the trial, 2 patients stopped treatment, 3 patients did not undergo the second visit due to the COVID pandemic. All of them had atherosclerotic vascular disease. Their mean (standard deviation) LDL-cholesterol concentration was 154 (85) mg/dL at baseline and was reduced by 76 (44) mg/dL in response to alirocumab treatment (p < 0.001, n = 19). P-selectin and vascular endothelial growth factors remained unchanged. Flow-dependent dilatation of the brachial artery (+41%, p = 0.241, n = 18), carotid intima-media thickness (p = 0.914, n = 18), and fractional anisotropy of the carotid artery (p = 0.358, n = 13) also did not significantly change. Conclusion: Despite a nominal amelioration for flow-dependent dilatation, significant effects of short-term treatment with alirocumab on vascular function were not detectable. More work would be needed to evaluate, whether fractional anisotropy may be useful in clinical atherosclerosis research.
Aims: To investigate the effects of the DPP-4 inhibitor Linagliptin in subjects with coronary artery disease (CAD) and early type 2 diabetes mellitus (T2DM) on a set of cardiovascular surrogate measurements. Materials and Methods: In this randomized, placebo-controlled, double-blind, single-center study, we included subjects with early diabetes (postchallenge diabetes (2h glucose >200mg/dl) or T2DM treated with diet only or on a stable dose of metformin monotherapy, HbA1c<75mmol/mol) and established CAD. Participants were randomized to receive either Linagliptin (5mg) once daily orally or placebo for 12 weeks. The primary outcome was the change in flow mediated dilatation (FMD). Results: We investigated 43 patients with a mean age of 6±8 years. FMD at baseline was 3.5±3.1% in the Linagliptin group vs. 4.0±2.9% in the placebo group. The change in mean FMD in the Linagliptin group (0.4±4.8%) was not significantly different compared to the change in the placebo group (-0.45±3.01%; p=0.486). No significant improvements were seen in the arginine bioavailability ratios (GABR); p=0.6and AOR; p=0.549), body weight, blood pressure and lipid parameters. Of note, HbA1c was significantly reduced in the linagliptin group (-1.5 vs. -0.4; p=0.026). Conclusion: Linagliptin treatment in subjects with CAD and early T2DM did not improve endothelial function or GABR. Disclosure F. Aberer: None. N.J. Tripolt: None. J. Url: None. R. Hödl: None. G. Dimsity: None. F. Aziz: None. R. Riedl: None. F. Hafner: None. D. Strunk: None. T. Stojakovic: None. M. Brodmann: None. H. Sourij: Speaker's Bureau; Self; Boehringer Ingelheim GmbH, Novo Nordisk A/S, Amgen Inc., Sanofi, MSD K.K.. Research Support; Self; AstraZeneca, Boehringer Ingelheim GmbH, MSD K.K., GI Dynamics Inc..
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