glucagon-like-peptide-1 and Coronary-Artery-Disease

To investigate the potential mechanism of once-weekly glucagon-like peptide-1 receptor agonists (GLP-1 RA) in the treatment of type 2 diabetes mellitus (T2DM) complicated with coronary artery disease (CAD).. We searched both Chinese and English databases for randomized controlled trials related to once-weekly GLP-1 RA for T2DM complicated with CAD to verify the safety and efficacy of GLP-1 RA. The underlying mechanism was analysed by network pharmacology.. In total, 13 studies with 35 563 participants were included in the analysis. The pooled analysis found that dulaglutide, exenatide and semaglutide outperformed placebo in cardiovascular outcomes in patients with T2DM, with a significant reduction in the incidence of non-fatal stroke (p < .00). Levels of cardiovascular risk factors were significantly reduced in the once-weekly GLP-1 RA group compared with the conventional treatment group (glycated haemoglobin: p < .00; fasting blood glucose: p < .00; weight: p < .00; systolic blood pressure: p < .00; total cholesterol: p < .00; low-density lipoprotein cholesterol: p < .00). Network pharmacology results were enriched to the renin-angiotensin system, and matrix metalloproteinase 2 and renin (REN) may be the key targets. In addition, four key targets of dulaglutide, five key targets of exenatide and two key targets of semaglutide were enriched.. Our study suggests that once-weekly GLP-1 RA may have a potential protective effect on cardiovascular events in patients with T2DM combined with CAD, possibly through the renin-angiotensin system. However, further research is needed to confirm these findings and determine cause and effect.

Topics: Cholesterol; Coronary Artery Disease; Diabetes Mellitus, Type 2; Exenatide; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; Glucagon-Like Peptides; Humans; Hypoglycemic Agents; Matrix Metalloproteinase 2; Renin-Angiotensin System

The continuous progress in cardiovascular risk prevention strategies has led to an impressive reduction in mortality and recurrent ischemic events in patients with coronary artery disease (CAD). However, the control of several cardiovascular risk factors remains suboptimal in many CAD patients, with a high rate of recurrent events, underlying the need for more new prevention strategies. The GAPS-I (glucagon-like peptide 1 analogues, antithrombotic agents, proprotein convertase subtilisin/kexin type 9 inhibitors, sodium glucose cotransporter type 2 inhibitors and immunomodulators) strategy offers a promising potential in patients with a high-residual cardiovascular risk, who are frequently encountered in daily practice, by offering an individualized and structured approach to addressing their individual risk factors. The current review summarizes the evidence to date on each of its components, with respect to clinical outcomes and economic feasibility. The current evidence points to an efficacy of GAPS-I in reducing major adverse cardiovascular events and mortality, without a compromise on safety, albeit with the need for longer follow-up data.

Topics: Cardiovascular Diseases; Cholesterol, LDL; Coronary Artery Disease; Fibrinolytic Agents; Glucagon-Like Peptide 1; Humans; Hypoglycemic Agents; Immunologic Factors; PCSK9 Inhibitors; Proprotein Convertase 9; Secondary Prevention; Sodium-Glucose Transporter 2 Inhibitors

Glucagon-like peptide-1 (GLP-1), is a hormone secreted by small intestine. Consumption of food or glucose stimulates synthesis and secretion of GLP-1 in the bloodstream, which in turn stimulates insulin secretion from pancreas and delays gastric emptying. Owing to the favorable spectrum of effects on reduction of hyperglycemia and body weight, GLP-1 mimetics are intensely pursued as therapies for the treatment of type 2 diabetes (T2DM). Even after intensive control of hyperglycemia, the propensity for cardiovascular disease cannot be totally negated in diabetic patients. A major reason for the cardiovascular disease risk in diabetic patients is underlying dyslipidemia, also termed as diabetic dyslipidemia. It is characterized by high concentrations of triglycerides and LDL cholesterol, and lowered HDL cholesterol in plasma, which are associated with hyperglycemia. Increased insulin resistance gives rise to increased free fatty acids in bloodstream, which is the main reason for the lipid changes appearing in diabetic dyslipidemia. The secondary complications like atherosclerosis and other cardiovascular diseases may be predicted with the blood concentrations of triglycerides and cholesterol, due to the correlation proven in clinic. Hence, new drugs that target diabetic dyslipidemia will always be useful in therapy. Apart from its actions on body weight and glucose, GLP-1 can also regulate cholesterol and triglycerides by numerous ways. Acute and long term treatment with either GLP-1 or its stable analogs reduced fasting as well as postprandial lipids in healthy as well as T2DM patients. GLP-1R signaling reduces VLDL-TG production rate from liver, reduces hepatic TG content by modulating key enzymes of lipid metabolism in liver, and impairs hepatocyte de novo lipogenesis and β-oxidation. GLP-1 can also modulate reverse cholesterol transport. Apart from these direct effects on lipid metabolism, GLP-1 also reduces atherosclerotic events by inhibiting expression of atherogenic inflammatory mediators, suppressing smooth muscle cell proliferation and stimulating NO production. This review mainly deliberates the association of GLP-1 in lipid regulation via lipid absorption, hepatic cholesterol metabolism, reverse cholesterol transport and progression of atherosclerosis.

Topics: Anticholesteremic Agents; Body Weight; Cholesterol; Coronary Artery Disease; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Dyslipidemias; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; Humans; Insulin Resistance; Lipid Metabolism; Receptors, Glucagon; Risk Factors; Signal Transduction; Treatment Outcome; Triglycerides

Type 2 diabetes mellitus is a progressive disease characterized by an impairment of insulin action, and failure of pancreatic β-cells to compensate for the enhanced insulin demand. Owing to the progressive nature of the disease, many individuals require insulin replacement therapy to maintain glycemic control. Intensification of treatment in these circumstances usually results in weight gain and increased risk of hypoglycemia, two undesirable events that are associated with a worse cardiovascular risk profile and decreased adherence to treatment. The introduction of glucagon-like peptide-1 (GLP-1) analogs (exenatide and liraglutide) into the diabetes market offers a new therapeutic approach to the treatment of type 2 diabetes. GLP-1 analogs increase insulin secretion and inhibit glucagon secretion in a glucose-dependent manner, thus conferring glycemic control with a low risk of hypoglycemia. GLP-1 analogs also promote weight loss, and have beneficial effects on blood pressure and cardiovascular risk markers. The combination of GLP-1 analogs and insulin might be highly effective to maintain glucose control, and to attenuate the adverse effects usually associated with insulin therapy. Data from both retrospective and prospective clinical studies support the therapeutic potential of the combination of GLP-1 analogs and insulin, usually showing beneficial effects on glycemic control associated with reduced weight gain, low incidence of hypoglycemia and, in established insulin therapy, reduction in insulin dose. In this review, the pathophysiological rationale for using the combination of GLP-1 analogs is discussed, and data from clinical studies that have evaluated the efficacy of this treatment strategy are summarized.

Topics: Contraindications; Coronary Artery Disease; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Drug Therapy, Combination; Glucagon-Like Peptide 1; Humans; Insulin

Various publications in 2009 showed that the treatment of type 2 diabetic (T2D) patients with macrovascular complications is still a controversial subject, whether with regard to the use of glitazones, to the best management strategy for T2D patients with stable coronary artery disease or to the use of incretin mimetic drugs in patients with heart disease. The Rosiglitazone Evaluated for Cardiac Outcomes and Regulation of glycemia in Diabetes study (RECORD) compared cardiovascular morbidity-mortality outcomes in patients taking rosiglitazone in combination with metformin or sulfonylurea versus metformin with sulfonylurea. The results showed that rosiglitazone was not inferior to the metformin-sulfonylurea combination in terms of mortality and cardiovascular hospitalization, but caution must be used when interpreting the results, as the event rate was low. The BARI 2D study (Bypass Angioplasty Revascularization Investigation 2 Diabetes) is a cardiovascular morbidity-mortality trial with the goal of determining the best strategy for blood glucose control and revascularization in T2D patients with stable coronary artery disease. The results of this trial showed that early revascularization is not clearly beneficial, except in a subgroup of patients in whom surgical revascularization is indicated. The use of GLP-1 analogs (Glucagon-Like Peptide-1) in the acute phase of myocardial ischemia in animal models provided promising results. Some clinical studies also suggest an improvement in cardiovascular risk factors with these treatments. Results from morbidity-mortality studies are needed to better assess the long-term efficiency of these new drugs.

Topics: Animals; Coronary Artery Disease; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Glucagon-Like Peptide 1; Heart Diseases; Humans; Hypoglycemic Agents; Risk Factors; Rosiglitazone; Thiazolidinediones

The relationship between plasma glucagon-like peptide-1 (GLP-1) and coronary plaque characteristics in humans remains unclear.. A total of 85 culprit coronary vessels excluding the 10-mm culprit segments in non-diabetic patients with acute coronary syndrome (ACS) were examined using integrated backscatter intravascular ultrasound, performed using a 40-MHz intravascular catheter before PCI. All patients underwent 75-g oral glucose tolerance test (OGTT), and the plasma GLP-1 response was evaluated on the basis of the area under the GLP-1 concentration-time curve (GLP-1 AUC) from 0 to 120 min. Patients in the low GLP-1 AUC tertile had a significantly greater percentage lipid area than did patients in the intermediate and high tertiles (low tertile vs. intermediate tertile vs. high tertile: 57.3 ± 12.1% vs. 47.2 ± 15.4% vs. 46.3 ± 12.7%, P<0.01, ANOVA) and a smaller percentage fibrosis area (38.1 ± 9.4% vs. 44.6 ± 11.5% vs. 45.7 ± 9.0%; P=0.01, ANOVA). On multiple regression analysis, low GLP-1 AUC tertile was independently associated with percentage lipid area.. Low plasma GLP-1 during 75-g OGTT is associated with increased lipid content in non-diabetic patients with ACS, suggesting that plaque vulnerability is increased in this subgroup of patients.

Topics: Acute Coronary Syndrome; Aged; Coronary Artery Disease; Diabetes Mellitus; Female; Glucagon-Like Peptide 1; Humans; Male; Middle Aged; Plaque, Atherosclerotic; Ultrasonography, Interventional

Glucagon-like peptide-1 (7-36) amide (GLP-1) protects against stunning and cumulative left ventricular dysfunction in humans. The mechanism remains uncertain but GLP-1 may act by opening mitochondrial K-ATP channels in a similar fashion to ischemic conditioning. We investigated whether blockade of K-ATP channels with glibenclamide abrogated the protective effect of GLP-1 in humans.. Thirty-two non-diabetic patients awaiting stenting of the left anterior descending artery (LAD) were allocated into 4 groups (control, glibenclamide, GLP-1, and GLP-1 + glibenclamide). Glibenclamide was given orally prior to the procedure. A left ventricular conductance catheter recorded pressure-volume loops during a 1-min low-pressure balloon occlusion (BO1) of the LAD. GLP-1 or saline was then infused for 30-min followed by a further 1-min balloon occlusion (BO2). In a non-invasive study, 10 non-diabetic patients were randomized to receive two dobutamine stress echocardiograms (DSE) during GLP-1 infusion with or without oral glibenclamide pretreatment.. GLP-1 prevented stunning even with glibenclamide pretreatment; the Δ % dP/dtmax 30-min post-BO1 normalized to baseline after GLP-1: 0.3 ± 6.8 % (p = 0.02) and GLP-1 + glibenclamide: -0.8 ± 9.0 % (p = 0.04) compared to control: -11.5 ± 10.0 %. GLP-1 also reduced cumulative stunning after BO2: -12.8 ± 10.5 % (p = 0.02) as did GLP-1 + glibenclamide: -14.9 ± 9.2 % (p = 0.02) compared to control: -25.7 ± 9.6 %. Glibenclamide alone was no different to control. Glibenclamide pretreatment did not affect global or regional systolic function after GLP-1 at peak DSE stress (EF 74.6 ± 6.4 vs. 74.0 ± 8.0, p = 0.76) or recovery (EF 61.9 ± 5.7 vs. 61.4 ± 5.6, p = 0.74).. Glibenclamide pretreatment does not abrogate the protective effect of GLP-1 in human models of non-lethal myocardial ischemia. Trial registration Clinicaltrials.gov Unique Identifier: NCT02128022.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Coronary Artery Disease; Coronary Vessels; Echocardiography, Stress; Female; Glucagon-Like Peptide 1; Glyburide; Humans; Male; Middle Aged; Myocardial Ischemia; Potassium Channels; Ventricular Dysfunction, Left; Young Adult

Enhancement of myocardial glucose uptake may reduce fatty acid oxidation and improve tolerance to ischemia. Hyperglycemia, in association with hyperinsulinemia, stimulates this metabolic change but may have deleterious effects on left ventricular (LV) function. The incretin hormone, glucagon-like peptide-1 (GLP-1), also has favorable cardiovascular effects, and has emerged as an alternative method of altering myocardial substrate utilization. In patients with coronary artery disease (CAD), we investigated: (1) the effect of a hyperinsulinemic hyperglycemic clamp (HHC) on myocardial performance during dobutamine stress echocardiography (DSE), and (2) whether an infusion of GLP-1(7-36) at the time of HHC protects against ischemic LV dysfunction during DSE in patients with type 2 diabetes mellitus (T2DM).. In study 1, twelve patients underwent two DSEs with tissue Doppler imaging (TDI)-one during the steady-state phase of a HHC. In study 2, ten patients with T2DM underwent two DSEs with TDI during the steady-state phase of a HHC. GLP-1(7-36) was infused intravenously at 1.2 pmol/kg/min during one of the scans. In both studies, global LV function was assessed by ejection fraction and mitral annular systolic velocity, and regional wall LV function was assessed using peak systolic velocity, strain and strain rate from 12 paired non-apical segments.. In study 1, the HHC (compared with control) increased glucose (13.0 ± 1.9 versus 4.8 ± 0.5 mmol/l, p < 0.0001) and insulin (1,212 ± 514 versus 114 ± 47 pmol/l, p = 0.01) concentrations, and reduced FFA levels (249 ± 175 versus 1,001 ± 333 μmol/l, p < 0.0001), but had no net effect on either global or regional LV function. In study 2, GLP-1 enhanced both global (ejection fraction, 77.5 ± 5.0 versus 71.3 ± 4.3%, p = 0.004) and regional (peak systolic strain -18.1 ± 6.6 versus -15.5 ± 5.4%, p < 0.0001) myocardial performance at peak stress and at 30 min recovery. These effects were predominantly driven by a reduction in contractile dysfunction in regions subject to demand ischemia.. In patients with CAD, hyperinsulinemic hyperglycemia has a neutral effect on LV function during DSE. However, GLP-1 at the time of hyperglycemia improves myocardial tolerance to demand ischemia in patients with T2DM.. http://www.isrctn.org . Unique identifier ISRCTN69686930.

Topics: Aged; Biomarkers; Biomechanical Phenomena; Blood Glucose; Coronary Artery Disease; Diabetes Mellitus, Type 2; Diabetic Cardiomyopathies; Echocardiography, Doppler, Color; Echocardiography, Stress; Female; Glucagon-Like Peptide 1; Glucose Clamp Technique; Humans; Hyperglycemia; Incretins; Infusions, Intravenous; Insulin; Male; Middle Aged; Myocardial Contraction; Peptide Fragments; Stroke Volume; Ventricular Dysfunction, Left; Ventricular Function, Left

The incretin hormone, glucagon-like peptide-1, promotes myocardial glucose uptake and may improve myocardial tolerance to ischemia. Endogenous glucagon-like peptide-1 (7-36) is augmented by pharmacological inhibition of dipeptidyl peptidase-4. We investigated whether chronic dipeptidyl peptidase-4 inhibition by sitagliptin protected against ischemic left ventricular dysfunction during dobutamine stress in patients with type 2 diabetes mellitus and coronary artery disease.. A total of 19 patients with type 2 diabetes mellitus underwent dobutamine stress echocardiography with tissue Doppler imaging on 2 separate occasions: the first (control) while receiving oral hypoglycemic agents, and the second after the addition of sitagliptin (100 mg once daily) for ≈4 weeks. Sitagliptin increased plasma glucagon-like peptide-1 (7-36) levels and, at peak stress, enhanced both global (ejection fraction, 70.5±7.0 versus 65.7±8.0%; P<0.0001; mitral annular systolic velocity, 11.7±2.6 versus 10.9±2.3 cm/s; P=0.01) and regional left ventricular function, assessed by peak systolic velocity and strain rate in 12 paired, nonapical segments. This was predominantly because of a cardioprotective effect on ischemic segments (strain rate in ischemic segments, -2.27±0.65 versus -1.98±0.58 s(-1); P=0.001), whereas no effect was seen in nonischemic segments (-2.19±0.48 versus -2.18±0.54 s(-1); P=0.87). At 30 minutes recovery, dipeptidyl peptidase-4 inhibition mitigated the postischemic stunning seen in the control scan.. The addition of dipeptidyl peptidase-4 inhibitor therapy with sitagliptin to the treatment regime of patients with type 2 diabetes mellitus and coronary artery disease is associated with a sustained improvement in myocardial performance during dobutamine stress and a reduction in postischemic stunning.. URL: http://www.isrctn.org. Unique identifier ISRCTN61646154.

Topics: Aged; Coronary Angiography; Coronary Artery Disease; Diabetes Mellitus, Type 2; Dipeptidyl Peptidase 4; Dipeptidyl-Peptidase IV Inhibitors; Echocardiography, Doppler; Echocardiography, Stress; Electrocardiography; Female; Follow-Up Studies; Glucagon-Like Peptide 1; Heart Ventricles; Humans; Male; Myocardial Ischemia; Pilot Projects; Pyrazines; Sitagliptin Phosphate; Stroke Volume; Treatment Outcome; Triazoles; Ventricular Dysfunction, Left

Sitagliptin has been widely used for the treatment of diabetes and shown recently to have beneficial pleiotropic outcomes on cardiovascular systems in experimental studies. However, little is known about the influence of sitagliptin on atherosclerosis-related cardiovascular diseases in a clinical setting. This study examined the effect of sitagliptin on carotid intima-media thickness (IMT). A total of 76 patients with clinically stable and documented coronary artery disease, who were newly diagnosed with impaired glucose tolerance or mild type 2 diabetes mellitus, were allocated, randomly, to receive either sitagliptin 100 mg/day or the placebo control. Common carotid IMT, glucose profiles, glycosylated hemoglobin (HbA1c), and lipid profiles were measured at baseline and repeated at 12 months. Sitagliptin-treated patients showed less IMT progression than the control group (p = 0.02). In addition, the sitagliptin group showed greater reductions in body weight (2.2%), 2-hour glucose levels on the 75-g oral glucose tolerance test (17.3%), HbA1c (4.7%), and low-density lipoprotein cholesterol levels (7.9%) from that at baseline. In conclusion, treatment with sitagliptin for 12 months was associated with a beneficial effect in the prevention of carotid IMT progression, compared with the diet control.

Topics: Aged; Aged, 80 and over; Blood Glucose; Carotid Arteries; Coronary Angiography; Coronary Artery Disease; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Glucagon-Like Peptide 1; Glucose Tolerance Test; Humans; Male; Middle Aged; Prospective Studies; Pyrazines; Sitagliptin Phosphate; Time Factors; Treatment Outcome; Triazoles; Tunica Intima; Ultrasonography

Glucagon-like peptide-1 (GLP-1) is an incretin hormone which has been shown to promote myocardial glucose uptake. Its pharmacological properties as a cardioprotective agent are attractive because it has a short half-life and there is minimal risk of hypoglycaemia.. To assess the hypothesis that intravenous infusion of GLP-1 would protect the heart from ischaemic left ventricular (LV) dysfunction during dobutamine stress echocardiography (DSE) in patients with coronary artery disease (CAD).. Randomised crossover study.. 14 patients with CAD and good LV function awaiting revascularisation underwent two DSE scans in a randomised order. GLP-1 was infused intravenously at 1.2 pmol/kg/min starting 30 min before the DSE for one of the scans and the other scan acted as a control.. Global and regional wall LV function assessed using tissue Doppler imaging at rest, peak stress and 30 min into recovery.. Global LV function was greater at peak stress during GLP-1 infusion compared with control (ejection fraction 77.0±4.4 vs 70.8±5.0%, p<0.0001; mitral annular systolic velocity 12.18±3.10 vs 11.31±3.11 cm/s, p=0.0004). GLP-1 infusion improved regional wall LV function in 12 non-apical segments assessed by velocity, strain and strain rate. This beneficial effect was predominantly seen in ischaemic segments. In recovery, infusion of GLP-1 mitigated the post-ischaemic stunning seen in the control scan.. Intravenous infusion of GLP-1 protects the heart from ischaemic LV dysfunction induced by dobutamine stress in patients with CAD.. URL: http://isrctn.org.. ISRCTN 69686930.

Topics: Cardiotonic Agents; Coronary Artery Disease; Coronary Circulation; Cross-Over Studies; Dobutamine; Echocardiography, Stress; Female; Follow-Up Studies; Glucagon-Like Peptide 1; Humans; Male; Middle Aged; Myocardial Reperfusion Injury; Prognosis; Prospective Studies

Postprandial lipemia is important in the development of coronary artery disease because of elevated postprandial triacylglycerol-rich plasma lipoproteins and suppressed HDL-cholesterol concentrations. We showed in healthy subjects a possible association between postprandial lipid metabolism and the responses of the duodenal incretin hormones glucagon-like peptide 1 (GLP-1) and gastric inhibitory polypeptide after meals rich in saturated and monounsaturated fatty acids (oleic acid), respectively.. The objective was to compare the postprandial responses (8 h) of glucose, insulin, fatty acids, triacylglycerol, gastric inhibitory polypeptide, and GLP-1 to saturated- and monounsaturated-rich test meals.. Twelve overweight patients with type 2 diabetes ingested 3 meals randomly: an energy-free soup with 50 g carbohydrate (control meal), the control meal plus 100 g butter, and the control meal plus 80 g olive oil. Triacylglycerol responses were measured in total plasma and in a chylomicron-rich and a chylomicron-poor fraction.. No significant differences in the glucose, insulin, or fatty acid responses to the 2 fat-rich meals were seen. The plasma triacylglycerol and chylomicron triacylglycerol responses were highest after the butter meal. HDL-cholesterol concentrations decreased significantly after the butter meal but did not change significantly after the olive oil meal. GLP-1 responses were highest after the olive oil meal.. Olive oil induced lower triacylglycerol concentrations and higher HDL-cholesterol concentrations than did butter, without eliciting significant changes in glucose, insulin, or fatty acids. Furthermore, olive oil induced higher concentrations of GLP-1, which may indicate a relation between fatty acid composition, incretin responses, and triacylglycerol metabolism postprandially in patients with type 2 diabetes.

Topics: Area Under Curve; Blood Glucose; Butter; Cholesterol, HDL; Chylomicrons; Coronary Artery Disease; Diabetes Mellitus; Diabetes Mellitus, Type 2; Fatty Acids; Fatty Acids, Monounsaturated; Female; Gastric Inhibitory Polypeptide; Glucagon; Glucagon-Like Peptide 1; Humans; Insulin; Male; Middle Aged; Obesity; Olive Oil; Peptide Fragments; Plant Oils; Postprandial Period; Protein Precursors; Triglycerides

The current research was designed to explore the relationship between the lipid accumulation index (LAP), coronary artery disease (CAD), and the triglyceride-glucose (TyG) index in patient with H-type hypertension.. From June 2021 to January 2022, our hospital's information management system collected data on 186 patients with essential hypertension. The participants were categorized into two groups (H-type hypertension (. There were statistically significant differences (. In conclusion, the LAP and TyG indexes were observed to be closely related to the degree of CAD in H-type individuals with hypertension, which can better understand the pathogenesis of coronary artery disease in patients with H-type hypertension and is of great significance for guiding clinical doctors to carry out personalized treatment and management.

Topics: Cholesterol, HDL; Constriction, Pathologic; Coronary Artery Disease; Glucagon-Like Peptide 1; Glucose; Homocysteine; Humans; Hypertension

Current guidelines for the management of hyperglycemia recommend the use of agents with proven cardiovascular (CV) benefit in patients with type 2 diabetes (T2D) and established CV disease. Although both glucagon-like peptide 1 receptor agonists (GLP-1 RA) and sodium-glucose co-transporter 2 inhibitors (SGLT2i) have been shown to reduce the risk of major adverse CV events (MACE) in high-risk populations with T2D, the ideal choice between the two classes for people with coronary artery disease remains controversial. SGLT2i reduce CV risk primarily through hemodynamic effects and changes in energy metabolism, making them the first choice in cases where heart failure or chronic kidney disease predominates. On the other hand, GLP-1 RA exert powerful anti-atherogenic properties that are the main drivers of their cardioprotection, and seem to have a consistent benefit in the atherosclerotic components of MACE. However, most people with diabetes and CV disease could take advantage of the complementary effects of the two drug categories on glycemic control, body weight, and diabetic complications. Future mechanistic studies and clinical head-to-head trials are expected to shed more light on this intriguing clinical dilemma and provide clear guidance for daily practice.

Topics: Animals; Cardiovascular Diseases; Coronary Artery Disease; Diabetes Mellitus, Type 2; Glucagon-Like Peptide 1; Horses; Humans; Hypoglycemic Agents; Sodium-Glucose Transporter 2 Inhibitors

The expression of glucagon‑like peptide receptors (GLP‑Rs) in epicardial fat (EF) and pericardial fat (PF) depots might be involved in the pathogenesis of cardiovascular diseases.. We sought to evaluate the messenger RNA (mRNA) expressions of GLP‑1R and GLP‑2R in EF and PF and their associations with the renin‑angiotensin‑aldosterone system (RAAS) in patients with multivessel coronary artery disease (CAD).. Consecutive stable patients with multivessel CAD requiring elective coronary artery bypass grafting were enrolled. Clinical data, anthropometric parameters, and the quantity of fat depots (assessed by cardiovascular magnetic resonance and abdominal ultrasound) were obtained. Fat samples (EF, PF, subcutaneous fat) were taken from patients during cardiac surgery. Relative mRNA expression of GLP‑1R, GLP‑2R, and RAAS components (angiotensin II receptor type 1, angiotensinogen, angiotensin I-converting enzyme 1, and angiotensinI-converting enzyme 2) were assessed in those fat depots.. Fifty‑three patients (64.7 [7.4] years) were included in the final analysis. We found that only the relative expression of GLP‑2R was lower in PF compared with subcutaneous fat (reference). Ultrasound abdominal fat depots were associated with both GLP‑1R and GLP‑2R in PF. GLP‑1R and GLP‑2R showed significant correlations with RAAS components in both EF and PF.. In stable patients with MVD, the relative mRNA expression for both GLP receptors revealed significant associations with majority of analysed RAAS components.

Topics: Adipose Tissue; Coronary Artery Disease; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; Glucagon-Like Peptide-2 Receptor; Humans; Pericardium; Renin-Angiotensin System

Topics: Coronary Artery Disease; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; Humans; Pericardium; Renin-Angiotensin System

To investigate the effect of GLP-1/GLP-1R on the polarization of macrophages in the occurrence and development of atherosclerosis.. Totally, 49 patients with coronary heart disease (CHD) and 52 cases of health control (HC) were recruited, all subjects accept coronary angiography gold standard inspection. One or more major coronary arteries (LM, LAD, LCx, and RCA) stenosis degree in 50% of patients as CHD group; the rest of the stenosis less than 50% or not seen obvious stenosis are assigned to the HC group. Flow cytometry were used to detect the percentage of (CD14+) M macrophages, (CD14+CD80+) M1 macrophages, (CD14+CD206+) M2 macrophages, and their surface GLP-1R expression differences in the two groups, using BD cytokine kit to detect the levels of IL-8, IL-1. GLP-1R expression on the surface of total macrophages and M2 macrophages was different between the CHD group and the HC group (. GLP-1R agonist is independent of the hypoglycemic effect of T2DM and has protective effect on cardiovascular system. GLP-1R may regulate the polarization of macrophages toward M2, thus playing a protective role in the progression of coronary atherosclerosis.

Topics: Adult; Aged; Cell Polarity; Coronary Artery Disease; Cytokines; Diabetes Mellitus, Type 2; Female; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; Humans; Lipids; Macrophages; Male; Middle Aged

Incretin therapies appear to provide cardioprotection and improve cardiovascular outcomes in patients with diabetes, but the mechanism of this effect remains elusive. We have previously shown that glucagon-like peptide (GLP)-1 is a coronary vasodilator and we sought to investigate if this is an adenosine-mediated effect.. We recruited 41 patients having percutaneous coronary intervention (PCI) for stable angina and allocated them into four groups administering a specific study-related infusion following successful PCI: GLP-1 infusion (Group G) (n = 10); Placebo, normal saline infusion (Group P) (n = 11); GLP-1 + Theophylline infusion (Group GT) (n = 10); and Theophylline infusion (Group T) (n = 10). A pressure wire assessment of coronary distal pressure and flow velocity (thermodilution transit time-Tmn) at rest and hyperaemia was performed after PCI and repeated following the study infusion to derive basal and index of microvascular resistance (BMR and IMR).. There were no significant differences in the demographics of patients recruited to our study. Most of the patients were not diabetic. GLP-1 caused significant reduction of resting Tmn that was not attenuated by theophylline: mean delta Tmn (SD) group G - 0.23 s (0.27) versus group GT - 0.18 s (0.37), p = 0.65. Theophylline alone (group T) did not significantly alter resting flow velocity compared to group GT: delta Tmn in group T 0.04 s (0.15), p = 0.30. The resulting decrease in BMR observed in group G persisted in group GT: - 20.83 mmHg s (24.54 vs. - 21.20 mmHg s (30.41), p = 0.97. GLP-1 did not increase circulating adenosine levels in group GT more than group T: delta median adenosine - 2.0 ng/ml (- 117.1, 14.8) versus - 0.5 ng/ml (- 19.6, 9.4); p = 0.60.. The vasodilatory effect of GLP-1 is not abolished by theophylline and GLP-1 does not increase adenosine levels, indicating an adenosine-independent mechanism of GLP-1 coronary vasodilatation.. The local research ethics committee approved the study (National Research Ethics Service-NRES Committee, East of England): REC reference 14/EE/0018. The study was performed according to institutional guidelines, was registered on http://www.clinicaltrials.gov (unique identifier: NCT03502083) and the study conformed to the principles outlined in the Declaration of Helsinki.

Topics: Adenosine; Aged; Aged, 80 and over; Coronary Artery Disease; Coronary Vessels; Female; Glucagon-Like Peptide 1; Humans; Male; Middle Aged; Purinergic P1 Receptor Antagonists; Signal Transduction; Theophylline; Vasodilation; Vasodilator Agents

Coronary artery disease (CAD) is the most frequent cause of morbidity and mortality worldwide. Lifestyle modifications and drug treatment of cardiovascular risk factors are able to effectively prevent CAD. The basis of prevention is the assessment of the individual cardiovascular risk, e.g. by using a validated risk score. Documented evidence for prevention of CAD is available for the control of hypertension using angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARB) and calcium antagonists, for the treatment of hypercholesterolemia using statins, ezetimibe and proprotein convertase subtilisin-kexin type 9 (PCSK-9) inhibitors and for the treatment of type 2 diabetes mellitus with metformin, sodium-glucose transporter 2 (SGLT-2) inhibitors and glucagon-like peptide 1 (GLP-1) agonists. There is no positive benefit-risk ratio for people with a low risk in the use of acetylsalicylic acid in primary prevention, in contrast to the positive recommendations for secondary prevention. There is no evidence for the efficacy of primary prevention with beta blockers, dipeptidyl peptidase 4 (DPP-4) inhibitors, glitazones, sulfonylureas or insulin. Similarly, there is no evidence for drug treatment of obesity, any supplementation with vitamins or hormone preparations or omega‑3 fatty acids.

Topics: Coronary Artery Disease; Diabetes Mellitus, Type 2; Glucagon-Like Peptide 1; Humans; Hypoglycemic Agents; Primary Prevention

The aim of the present study was to assess the risk of overall mortality, coronary artery disease (CAD), and congestive heart failure (CHF) in patients with type 2 diabetes mellitus (T2DM) treated with metformin (MF) and an additional antidiabetic agent.. A retrospective cohort study was conducted using an academic health center enterprise-wide electronic health record (EHR) system to identify 13,185 adult patients (>18 years) with T2DM from January 2008 to June 2013 and received a prescription for MF in combination with a sulfonylurea (SU; n = 9419), thiazolidinedione (TZD; n = 1846), dipeptidyl peptidase-4 inhibitor (DPP-4i; n = 1487), or a glucagon-like peptide-1 receptor agonist (GLP-1a; n = 433). Multivariate Cox models with propensity analysis were used to compare cohorts, with MF+SU serving as the comparator group.. The mean (±SD) age was 60.6 ± 12.6 years, with 54.6% male and 75.8% Caucasians. The median follow-up was 4 years. There were 1077 deaths, 1733 CAD events, and 528 CHF events in 55,100 person-years of follow-up. A higher risk of CHF was observed with MF+DPP-4i use (hazard ratio [HR] 1.104; 95% confidence interval [CI] 1.04-1.17; P = 0.001). A trend towards improved overall survival for users of MF+TZD (HR 0.86; 95% CI 0.74-1.0; P = 0.05) and MF+GLP-1a (HR 0.569; 95% CI 0.30-1.07; P = 0.08) was observed. No significant differences in the risk of CAD were identified.. Consistent with recent studies, our results raise concern for an increased risk of CHF with use of DPP-4i.

Topics: Aged; Coronary Artery Disease; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Drug Therapy, Combination; Female; Glucagon-Like Peptide 1; Heart Failure; Humans; Hypoglycemic Agents; Male; Metformin; Middle Aged; Multivariate Analysis; Outcome Assessment, Health Care; Peptide Fragments; Proportional Hazards Models; Retrospective Studies; Risk Factors; Sulfonylurea Compounds; Survival Rate; Thiazolidinediones

Topics: Aged; Case-Control Studies; Coronary Artery Disease; Cross-Sectional Studies; Fasting; Female; Glucagon-Like Peptide 1; Glucose Tolerance Test; Humans; Male; Middle Aged

GLP-1 is an incretine hormone which gets secreted from intestinal L-cells in response to nutritional stimuli leading to pancreatic insulin secretion and suppression of glucagon release. GLP-1 further inhibits gastric motility and reduces appetite which in conjunction improves postprandial glucose metabolism. Additional vasoprotective effects have been described for GLP-1 in experimental models. Despite these vasoprotective actions, associations between endogenous levels of GLP-1 and cardiovascular disease have yet not been investigated in humans which was the aim of the present study.. GLP-1 serum levels were assessed in a cohort of 303 patients receiving coronary CT-angiography due to typical or atypical chest pain.. GLP-1 was found to be positively associated with total coronary plaque burden in a fully adjusted model containing age, sex, BMI, hypertension, diabetes mellitus, smoking, triglycerides, LDL-C (low density lipoprotein cholesterol), hsCRP (high-sensitive C-reactive protein), and eGFR (estimated glomerular filtration rate) (OR: 2.53 (95% CI: 1.12 - 6.08; p = 0.03).. Circulating GLP-1 was found to be positivity associated with coronary atherosclerosis in humans. The clinical relevance of this observation needs further investigations.

Topics: Aged; Biomarkers; Coronary Angiography; Coronary Artery Disease; Coronary Vessels; Female; Glucagon-Like Peptide 1; Humans; Male; Middle Aged; Multidetector Computed Tomography; Plaque, Atherosclerotic; Severity of Illness Index

Glucagon-like peptide-1 (GLP-1) is an incretin hormone secreted postprandially that promotes myocardial glucose uptake. The active amide GLP-1 (7-36) is degraded by the enzyme DPP-4, and drugs that inhibit this enzyme (such as sitagliptin) have been introduced to treat type 2 diabetes. We assessed the hypothesis that increasing the plasma concentration of GLP-1 by DPP-4 inhibition would protect the heart from ischemic left ventricular (LV) dysfunction during dobutamine stress echocardiography in patients with coronary artery disease.. Fourteen patients with coronary artery disease and preserved LV function awaiting revascularization were studied. After either a single dose of 100 mg sitagliptin or placebo, 75 g of glucose was given orally to promote GLP-1 secretion and dobutamine stress echocardiography was conducted with tissue Doppler imaging at rest, peak stress, and 30 minutes. After sitagliptin, plasma GLP-1 (7-36) was increased at peak stress (16.5+/-10.7 versus 9.7+/-8.7 pg/mL; P=0.003) and in recovery (12.4+/-5.5 versus 9.0+/-5.5 pg/mL; P=0.01), and the LV response to stress was enhanced (ejection fraction, 72.6+/-7.2 versus 63.9+/-7.9%, P=0.0001; mitral annular systolic velocity, 12.54+/-3.18 versus 11.49+/-2.52 cm/s; P=0.0006). DPP-4 inhibition also improved LV regional function in the 12 paired nonapical segments assessed by peak systolic tissue Doppler (velocity, 10.56+/-4.49 versus 9.81+/-4.26 cm/s, P=0.002; strain, -15.9+/-6.3 versus -14.6+/-6.6%, P=0.01; strain rate, -2.04+/-1.04 versus -1.75+/-0.98 s(-1), P=0.0003). This was predominantly due to a cardioprotective effect on ischemic segments (velocity in ischemic segments, 9.77+/-4.18 versus 8.74+/-3.87, P=0.007; velocity in nonischemic segments, 11.51+/-4.70 versus 11.14+/-4.38, P=0.14). In recovery, sitagliptin attenuated the postischemic stunning seen after the control study.. The augmentation of GLP-1 (7-36) by inhibition of DPP-4 improves global and regional LV performance in response to stress and mitigates postischemic stunning in humans with coronary artery disease. Clinical Trial Registration- URL: http://www.isrctn.org. Unique identifier: ISRCTN78649100.

Topics: Coronary Artery Disease; Dipeptidyl-Peptidase IV Inhibitors; Echocardiography, Stress; Female; Glucagon-Like Peptide 1; Humans; Male; Middle Aged; Myocardial Stunning; Pilot Projects; Pyrazines; Reproducibility of Results; Sitagliptin Phosphate; Triazoles; Ventricular Dysfunction, Left