Tirzepatide reduced systolic blood pressure by up to 12.6 mmHg from baseline, an effect primarily mediated by weight loss and independent of concurrent antihypertensive medication use.
Does tirzepatide reduce systolic blood pressure through weight-loss dependent or independent effects in patients with type 2 diabetes?
Tirzepatide significantly reduces systolic blood pressure in patients with type 2 diabetes, an effect driven by both weight loss and weight-independent mechanisms, without increasing the risk of hypotension in patients with lower baseline blood pressure.
Effect estimate: MD -3.1 to -11.5 mmHg (15 mg vs comparators)
p-value: p=<0.001
BACKGROUND: Tirzepatide, a once-weekly glucose-dependent insulinotropic polypeptide/ glucagon-like peptide-1 receptor agonist, is approved in the United States, Europe and Japan for the treatment of type 2 diabetes. Across the SURPASS-1 to -5 clinical studies, tirzepatide 5, 10 and 15 mg demonstrated significant improvements in glycated haemoglobin A1c (HbA1c) (- 1.9 to - 2.6%), body weight (- 6.6 to - 13.9%) and systolic blood pressure (SBP) (- 2.8 to - 12.6 mmHg) at the end of study treatment. METHODS: Post-hoc mediation analyses were conducted to evaluate weight-loss dependent and weight-loss independent effects of tirzepatide on SBP reductions across the 5 SURPASS studies. The safety population (all randomized patients who took at least 1 dose of study drug) of each study was analyzed. Additional analyses were conducted at individual study level or pooled across 5 SURPASS trials. RESULTS: The difference in mean SBP change from baseline at 40 weeks (total effect) between the tirzepatide and comparator groups was - 1.3 to - 5.1 mmHg (tirzepatide 5 mg), - 1.7 to - 6.5 mmHg (tirzepatide 10 mg) and - 3.1 to - 11.5 mmHg (tirzepatide 15 mg). These SBP reductions were primarily mediated through weight loss, with different degrees of contributions from weight-loss independent effects across the different trials. In the SURPASS-4 study, which enrolled patients with established cardiovascular disease, weight-loss independent effects explained 33% to 57% of difference in SBP change between tirzepatide and insulin glargine groups. In a pooled analysis of the SURPASS-1 to -5 studies, there was a significant (p 140 mmHg), while those in the first quartile of baseline SBP category (< 122 mmHg) observed no further decrease in SBP. CONCLUSIONS: Tirzepatide-induced SBP reduction was primarily mediated through weight loss, with different degrees of contributions from weight-loss independent effects across the different trials. SBP reduction was not dependent on antihypertensive medication use but dependent on baseline SBP value, alleviating theoretical concerns of hypotension.
Lingvay et al. (Fri,) conducted a other in Type 2 diabetes (n=6,263). Tirzepatide vs. Placebo, semaglutide 1 mg, insulin degludec, or insulin glargine was evaluated on Difference in mean systolic blood pressure change from baseline at 40/42 weeks (MD -3.1 to -11.5 mmHg (15 mg vs comparators), p=<0.001). Tirzepatide reduced systolic blood pressure by up to 12.6 mmHg from baseline, an effect primarily mediated by weight loss and independent of concurrent antihypertensive medication use.