Tirzepatide and cardiometabolic parameters in obesity: Summary of current evidence

Abstract

Globally, cardiovascular diseases (CVDs) account for around one-third of all deaths. Clinical trial evidence suggests that treatment of people with obesity or type 2 diabetes (T2D) and CVD with glucagon-like peptide-1 (GLP-1) receptor agonists reduces the risk of major adverse cardiovascular events, heart failure outcomes and all-cause mortality. Tirzepatide is a once-weekly, dual glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 receptor agonist that has demonstrated dose-dependent efficacy in people with obesity, T2D or both, in terms of glycaemic control and bodyweight reduction in clinical trials. This narrative review summarizes the current evidence regarding the effects of tirzepatide treatment on cardiometabolic parameters, including lipid profile, blood pressure and markers of renal function. Additionally, it summarizes the reported impact of tirzepatide treatment on other relevant parameters, such as body composition, liver fat, progression to T2D among individuals with prediabetes, and incidence of heart failure events. Considering the changing landscape of clinical trial evidence of tirzepatide's effects, this review aims to compile the available evidence, which suggests a promising outlook for the cardiometabolic benefits of tirzepatide.

Keywords: cardiometabolic factors; cardiovascular disease; obesity; tirzepatide.

FIGURE 1

Summary of the treatment effects of tirzepatide relative to comparators on cardiometabolic parameters among people with obesity or overweight with and without T2D: Evidence from randomized clinical trials. Ranges across studies for changes from baseline, or for estimated treatment differences or absolute differences (regardless of efficacy estimand or treatment‐regimen estimand) for tirzepatide (15 mg) versus comparator groups are presented for the cardiometabolic parameters. Please note that ranges may vary depending on the characteristics of the study population and treatment duration. Study‐specific detailed results can be found in Table S1. Results are presented for the efficacy estimand to provide clinicians with insights into what can be expected for patients who stay on treatment. ¹For people with obesity and T2D, changes from baseline in SBP and DBP values are presented for the treatment‐regimen estimand. ²Reduction in risk of T2D in participants with prediabetes in SURMOUNT‐1 was assessed based on glycated haemoglobin and fasting serum glucose levels, and serum glucose levels in a 2‐h oral glucose tolerance test; diagnosis of diabetes was based on ADA guidelines. ADA, American Diabetes Association; CI, confidence interval; DBP, diastolic blood pressure; diff, difference; eGFR, estimated glomerular filtration rate; HbA1c, glycated haemoglobin; HDL‐C, high‐density lipoprotein cholesterol; HR, hazard ratio; KCCQ‐CSS, Kansas City Cardiomyopathy Questionnaire clinical summary score; LDL‐C, low‐density lipoprotein cholesterol; SBP, systolic blood pressure; T2D, type 2 diabetes; UACR, urine albumin–creatinine ratio.