Dulaglutide lowers SBP and pulse pressure independent of weight reduction among diabetes patients

A new study published in Cardiovascular Diabetology suggests that in all of the placebo-controlled studies conducted as part of the AWARD program, dulaglutide 1.5 mg decreased systolic blood pressure (SBP) and pulse pressure in type 2 diabetes (T2D) patients. 

Glucagon-like peptide-1 receptor agonists may lower blood pressure and reduce weight in type 2 diabetic patients. The main goal of this study, which was carried out by Keith Ferdinand and colleagues were to ascertain the effects of a 6-month therapy with dulaglutide 1.5 mg on patients with T2D that were weight-dependent and weight-independent.

To determine the weight-dependent (i.e., mediated by weight) and weight-independent effects of dulaglutide vs. placebo on change from baseline for systolic blood pressure, diastolic blood pressure (DBP), and pulse pressure, mediation analysis was performed for five randomized, placebo-controlled trials of dulaglutide 1.5 mg. These findings were merged using a random-effects meta-analysis. Mediation analysis was initially used in AWARD-11 to assess the weight-dependent and weight-independent impacts of dulaglutide 4.5 mg vs. 1.5 mg, then an indirect comparison with the mediation result for dulaglutide 1.5 mg vs. placebo was made. This investigation was done to determine if there was a dosage response between dulaglutide 4.5 mg and placebo.

The key findings of this study were:

The studies' baseline characteristics were fairly consistent. 

The overall treatment impact of dulaglutide 1.5 mg after adjusting for placebo on SBP was - 2.6 mmHg and was ascribed to both a weight-dependent effect and a weight-independent effect, accounting for 36% and 64% of the total effect, respectively, in the mediation meta-analysis of placebo-controlled studies. 

Dulaglutide's overall therapeutic impact on pulse pressure was 14% weight-dependent and 86% weight-independent. 

With just a little weight-mediated effect, dulaglutide therapy had little influence on DBP. 

A drop in SBP and pulse pressure was seen with dulaglutide 4.5 mg that was greater than that with dulaglutide 1.5 mg, which was predominantly weight mediated.

The bulk of the effect of dulaglutide 1.5 mg on SBP and pulse pressure was independent of weight, however up to one third of the effect was attributed to weight reduction. Future strategies for treating hypertension may benefit from a better knowledge of the pleotropic effects of GLP-1 RA that lower blood pressure.

Reference: 

Ferdinand, K. C., Dunn, J., Nicolay, C., Sam, F., Blue, E. K., & Wang, H. (2023). Weight-dependent and weight-independent effects of dulaglutide on blood pressure in patients with type 2 diabetes. In Cardiovascular Diabetology (Vol. 22, Issue 1). Springer Science and Business Media LLC. https://doi.org/10.1186/s12933-023-01775-x