Comparison of tirzepatide and dulaglutide on major adverse cardiovascular events in participants with type 2 diabetes and atherosclerotic cardiovascular disease: SURPASS-CVOT design and baseline characteristics.

BACKGROUND: Tirzepatide, a once-weekly GIP/GLP-1 receptor agonist, reduces blood glucose and body weight in people with type 2 diabetes. The cardiovascular (CV) safety and efficacy of tirzepatide have not been definitively assessed in a cardiovascular outcomes trial. METHODS: Tirzepatide is being studied in a randomized, double-blind, active-controlled CV outcomes trial. People with type 2 diabetes aged ≥40 years, with established atherosclerotic CV disease, HbA1c ≥7% to ≤10.5%, and body mass index ≥25 kg/m2 were randomized 1:1 to once weekly subcutaneous injection of either tirzepatide up to 15 mg or dulaglutide 1.5 mg. The primary outcome is time to first occurrence of any major adverse cardiovascular event (MACE), defined as CV death, myocardial infarction, or stroke. The trial is event-driven and planned to continue until ≥1,615 participants experience an adjudication-confirmed component of MACE. The primary analysis is noninferiority for time to first MACE of tirzepatide vs dulaglutide by demonstrating an upper confidence limit <1.05, which will also confirm superiority vs a putative placebo, and also to determine whether tirzepatide produces a greater CV benefit than dulaglutide (superiority analysis). RESULTS: Over 2 years, 13,299 people at 640 sites in 30 countries across all world regions were randomized. The mean age of randomized participants at baseline was 64.1 years, diabetes duration 14.7 years, HbA1c 8.4%, and BMI 32.6 kg/m2. Overall, 65.0% had coronary disease, of whom 47.3% reported prior myocardial infarction and 57.4% had prior coronary revascularization. 19.1% of participants had a prior stroke and 25.3% had peripheral artery disease. The trial is fully recruited and ongoing. CONCLUSION: SURPASS-CVOT will provide definitive evidence as to the CV safety and efficacy of tirzepatide as compared with dulaglutide, a GLP-1 receptor agonist with established CV benefit.

Early Detection of Left Ventricular Dysfunction in Diabetes Mellitus Patients with Normal Ejection Fraction, Stratified by BMI: A Preliminary Speckle Tracking Echocardiography Study.

BACKGROUND: Diabetes mellitus (DM) represents by itself a major risk factor for cardiovascular events and the coexistence of obesity with consequent left ventricular volumetric overload could be responsible for further damages on left ventricular function. Aim of this study was to demonstrate the effect of body mass index (BMI) on left ventricular function in diabetes patients with no cardiovascular complications and with normal ejection fraction (EF). MATERIALS AND METHODS: We evaluated 71 stable asymptomatic diabetes patients in optimal medical treatment and 24 healthy controls (C) (45% females; mean age: 58.4 +/- 9.4 years; BMI: 23.5 +/- 1.5). We stratified diabetes patients into two groups according to BMI: BMI <30 kg/m2 (A: 44 patients; 47% females; mean age: 60.9 +/- 6.6 years; BMI: 25.7 +/- 1.9; Diabetes duration: 9.1 +/- 9.5 years); BMI >30 kg/m2 (B: 27 patients; 37% females; mean age: 56.2 +/- 7.8 years; BMI: 33.0 +/- 2.1; Diabetes duration: 8.5 +/- 5.2 years). The following parameters were evaluated by conventional two dimensional (2D) echocardiography (GE VIVID 7) and tissue Doppler imaging (TDI): left ventricular dimensions (LVIDd; PWTd; IVSd), Left Ventricular Volumes (EDV, ESV), EF (by biplane Simpson's method), Left Ventricular Mass (by ASE formula), peak mitral annular velocity at septal and lateral levels (Sm and Sl). Global longitudinal strain (GLS) was obtained off line by Speckle tracking imaging method using Echopac 10 software. RESULTS: Groups A, B were comparable for diabetes duration and glycated hemoglobin level, history of hypertension, and lipid profile. The EF was similar in the three groups, (A: 64 +/- 6%; B: 63 +/- 4%; C: 61 +/-5%; P= NS). LVMass2.7 indexed for height was significantly higher in A and B in comparison with C (A: 45.2 +/- 8.1 g/m2.7; B: 46.1 +/- 9.6 g/m2.7; C: 39.5 +/- 4.9 g/m2.7; P < 0.05). The stroke volume index (SVi) was significantly lower in B vs A (B: 35.3 +/- 5.7 ml/m2; A: 39.3 +/7.1 ml/m2; P = 0.033). GLS was significantly lower in group B respect A and C (C: 20.9 +/- 1.3%; A: -20.3+/-2.6%; B: -19 +/- 2; P < 0.05; P < 0.01). CONCLUSIONS: In uncomplicated asymptomatic DM patients, the presence of first degree obesity plays an incremental role in adversely affecting left ventricular function and remodeling. The conventional echocardiographic methods such as the EF and the TDI are not so sensitive to identify the early LV dysfunction such as the evaluation of GLS by Speckle Tracking echocardiography. The longitudinal subendocardial fibers dysfunction in diabetes/obese patients could be derived by the complex interaction between metabolic (diabetes) and hemodynamic/endocrine abnormalities.