incretins and empagliflozin

Diabetes treatments aim at preventing undesirable metabolic effects of hyperglycemia and at preventing/reducing tissue damage, including cardiovascular (CV) events. For approval, novel diabetes drugs undergo early systematic investigation to assess CV safety. This review provides an updated analysis of the results of recent studies examining novel diabetes medications and CV outcomes.. The new regulatory guidelines enforce adjudication of all CV events when testing novel diabetes drugs. Endpoints of CV mortality, myocardial infarction (MI), stroke and hospitalization for heart failure (HF) were included in the most recent clinical studies on novel antihyperglycemics. These are: the incretin mimetics glucagon-like peptide 1 (GLP-1) receptor agonists (GLP1-RA), the incretin enhancers dipeptidylpeptidase-4 (DPP-4) inhibitors (DPP4-I or gliptins), and the sodium-glucose cotransporter (SGLT2) inhibitors (SGLT2-I or gliflozins). The studies ELIXA and EXAMINE, testing lixisenatide and alogliptin, respectively, revealed non-inferiority versus placebo in terms of CV safety. The SAVOR-TIMI 53 results confirmed overall CV safety of saxagliptin, but raised a warning related to the increase in the risk of hospitalization for HF in the saxagliptin group. Recently, TECOS revealed a particularly favorable CV profile for sitagliptin while EMPA-REG showed a significant CV risk reduction in empagliflozin treated subjects. Ongoing studies will provide additional data on CV safety for other GLP1-RAs, DPP4-I and SGLT2-I.. Results of safety outcome studies focused on CV events, including HF and mortality for CV causes, are not homogeneous. A critical analysis of these studies may help cardiologists and diabetes specialists to adapt their therapeutic choices to individual patients.

Topics: Benzhydryl Compounds; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Glucosides; Humans; Hypoglycemic Agents; Incretins; Patient Safety; Patient Selection; Risk Assessment; Risk Factors; Sitagliptin Phosphate; Treatment Outcome

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are the most recent addition to the therapeutic options available for the treatment of type 2 diabetes and became available after the introduction of incretin-based therapies, dipeptidyl peptidase 4 inhibitors and glucagon-like peptide 1 receptor agonists (GLP-1 RAs). These agents have potential advantages with regard to their weight loss-promoting effect, low risk of hypoglycemia, reduction in blood pressure, and reduction in cardiovascular events in high-risk patients (with empagliflozin). Apart from these clinically important outcomes, they may also correct core defects present in type 2 diabetes (i.e., improvement in β-cell function and insulin sensitivity). They do, however, have some adverse effects, notably, nausea with GLP-1 RAs and genital tract infections and potential for volume depletion with SGLT2i. Whether incretin-based therapies are associated with an increased risk of pancreatitis is unclear. Most recently, diabetic ketoacidosis has been reported with SGLT2i. Therefore, a key clinical question in relation to guidelines is whether these clinical advantages, in the context of the adverse effect profile, outweigh the additional cost compared with older, more established therapies. This article reviews the therapeutic rationale for the use of these newer drugs for diabetes treatment, considers their place in current guidelines, and discusses how this may change as new data emerge about their long-term efficacy and safety from ongoing outcome trials.

Topics: Algorithms; Benzhydryl Compounds; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Drug Therapy, Combination; Glucosides; Humans; Hypoglycemia; Hypoglycemic Agents; Incretins; Receptors, Glucagon; Sodium-Glucose Transporter 2; Sodium-Glucose Transporter 2 Inhibitors

Topics: Adult; Aged; Arterial Pressure; Arteries; Benzhydryl Compounds; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Endothelial Cells; Female; Glucagon-Like Peptide-1 Receptor; Glucosides; Glycocalyx; Greece; Humans; Incretins; Insulin; Liraglutide; Male; Metformin; Middle Aged; Recovery of Function; Sodium-Glucose Transporter 2 Inhibitors; Time Factors; Treatment Outcome; Vascular Stiffness; Ventricular Function, Left

Cardiovascular protection following empagliflozin therapy is not entirely attributable to the glucose lowering effect. Increased hematocrit might influence the shear stress that is the main force acting on the endothelium, regulating its anti-atherogenic function.. We designed the study with the aim of investigating the effect of empagliflozin on blood viscosity and shear stress in the carotid arteries. A secondary endpoint was the effect of empagliflozin on carotid artery wall thickness.. The study was a non-randomized, open, prospective cohort study including 35 type 2 diabetic outpatients who were offered empagliflozin or incretin-based therapy (7 liraglutide, 8 sitagliptin) in combination with insulin and metformin. Blood viscosity, shear stress and carotid wall thickness were measured at baseline and at 1 and 3 months of treatment. Blood viscosity was measured with a viscometer, and shear stress was calculated using a validated formula. Intima-media thickness (IMT) of the carotid artery was detected by ultrasound and was measured with dedicated software.. Blood viscosity (4.87 ± 0.57 vs 5.32 ± 0.66 cP, p < 0.02) and shear stress significantly increased in the Empagliflozin group while no change was detected in the Control group (4.66 ± 0.56 vs 4.98 ± 0.73 cP, p = NS). IMT significantly decreased in the Empagliflozin group after 1 and 3 months (baseline: 831 ± 156, 1-month 793 ± 150, 3-month 766 ± 127 μm; p < 0.0001), while in the liraglutide group, IMT significantly decreased only after 3 months (baseline 879 ± 120; 1-month 861 ± 163; 3-month 802 ± 114 μm; p < 0.001). In the sitagliptin group, IMT remained almost unchanged (baseline 901 ± 135; 1-month 902 ± 129; 3-month 880 ± 140 μm; p = NS).. This study is the first to describe a direct effect of empagliflozin on blood viscosity and wall shear stress. Furthermore, IMT was markedly reduced early on in the Empagliflozin group.

Topics: Aged; Benzhydryl Compounds; Blood Viscosity; Carotid Artery, Common; Carotid Intima-Media Thickness; Diabetes Mellitus, Type 2; Female; Glucosides; Humans; Incretins; Liraglutide; Male; Middle Aged; Prospective Studies; Regional Blood Flow; Sitagliptin Phosphate; Sodium-Glucose Transporter 2 Inhibitors; Stress, Mechanical; Time Factors; Treatment Outcome

Topics: Benzhydryl Compounds; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Glucosides; Heart Failure; Humans; Hypoglycemic Agents; Incretins; Randomized Controlled Trials as Topic; Sodium-Glucose Transporter 2; Sodium-Glucose Transporter 2 Inhibitors; Survival Analysis

Topics: Benzhydryl Compounds; Cardiovascular Diseases; Clinical Trials as Topic; Diabetes Mellitus, Type 2; Glucosides; Humans; Hypoglycemic Agents; Incretins; Liraglutide; Protective Factors; Risk Factors; Treatment Outcome