Tirzepatide decreases systolic and diastolic blood pressure.

Tirzepatide is a newer glucose-lowering medication with agonist activity on the glucagon-like peptide (GLP)−1 receptor as well as on the glucose-dependent insulinotropic polypeptide (GIP) receptor. Tirzepatide exerts superior glycated hemoglobin (HbA1c) and overall plasma glucose lowering effects compared to GLP-1 agonists or basal insulin therapy. Furthermore, exploratory analyses have demonstrated that compared to insulin glargine, tirzepatide has a greater anti-albuminuric effects, and attenuates the decline in estimated glomerular filtration rate (eGFR). From a kidney perspective, in post-hoc analyses of data from SURPASS-4 clinical trial, eGFR decline by slope was less with tirzepatide compared to insulin glargine (−1.4 ml/min/1.73 m2 vs. −3.6 ml/min/1.73m2 in insulin glargine) similar to urinary albumin-to-creatinine ratio (95% CI, 26.0 to 48.7%). Although the exact mechanisms responsible for this nephroprotective profile are largely unknown, several factors may be responsible including better glycaemic control, suppression of pro-inflammatory cytokines, reactive oxygen species, and the renin-angiotensin-aldosterone system, decline in glomerular hypertension and reduction in body weight. Cardioprotective effects of tirzepatide may also be attributable actions on GLP-1 receptors inhibiting the formation, progression, and rupture of atherosclerotic plaques [ 1 Dahl D. Onishi Y. Norwood P. Huh R. Bray R. Patel H. et al. Effect of subcutaneous tirzepatide vs placebo added to titrated insulin glargine on glycemic control in patients with type 2 diabetes: the surpass-5 randomized clinical Trial. JAMA. 2022; 327: 534-545 Crossref PubMed Scopus (88) Google Scholar , 2 Del Prato S. Kahn S.E. Pavo I. Weerakkody G.J. Yang Z. Doupis J. et al. Tirzepatide versus insulin glargine in type 2 diabetes and increased cardiovascular risk (SURPASS-4): a randomised, open-label, parallel-group, multicentre, phase 3 trial. Lancet. 2021; 398: 1811-1824 Abstract Full Text Full Text PDF PubMed Scopus (123) Google Scholar , 3 Frías J.P. Davies M.J. Rosenstock J. Pérez Manghi F.C. Fernández Landó L. Bergman B.K. et al. Tirzepatide versus semaglutide once weekly in patients with type 2 diabetes. N Engl J Med. 2021; 385: 503-515 Crossref PubMed Scopus (313) Google Scholar , 4 Frias J.P. Nauck M.A. Van J. Kutner M.E. Cui X. Benson C. et al. Efficacy and safety of LY3298176, a novel dual GIP and GLP-1 receptor agonist, in patients with type 2 diabetes: a randomised, placebo-controlled and active comparator-controlled phase 2 trial. Lancet. 2018; 392: 2180-2193 Abstract Full Text Full Text PDF PubMed Scopus (423) Google Scholar , 5 Inagaki N. Takeuchi M. Oura T. Imaoka T. Seino Y Efficacy and safety of tirzepatide monotherapy compared with dulaglutide in Japanese patients with type 2 diabetes (SURPASS J-mono): a double-blind, multicentre, randomised, phase 3 trial. Lancet Diabetes Endocrinol. 2022; 10: 623-633 Abstract Full Text Full Text PDF PubMed Scopus (23) Google Scholar ].