Liraglutide Lowers SBP in Patients With Type 2 Diabetes

Recent research showed the glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide caused rapid and sustained reductions in systolic blood pressure (SBP) in patients with type 2 diabetes.

The study involved the pooled analysis of 2,792 total patients involved in the 6 phase 3 clinical studies of the 2009 Liraglutide Effect and Action in Diabetes (LEAD) trials: 898 patients received liraglutide 1.2 mg, 1,366 received liraglutide 1.8 mg, and 528 received placebo. The average baseline SBP was 133 mmHg in the liraglutide 1.2 mg group, 134 mmHg in the liraglutide 1.8 mg group, and 135 mmHg in the placebo group.

After 2 weeks, SBP decreased by 2.6 and 3.3 mmHg with liraglutide 1.2 mg and 1.8 mg, respectively, compared with 1.4 mmHg with placebo. After 26 weeks, SBP was reduced by an average of 2.7 mmHg and 2.9 mmHg with liraglutide 1.2 mg and 1.8 mg, respectively, compared with 0.5 mmHg with placebo. Liraglutide lowered SBP more than sulfonylurea glimepiride, and its higher dose had greater SBP-lowering effects than insulin glargine and rosiglitazone, noted the study.

Patients who experienced drops in SBP with liraglutide also lost weight, according to the study, although the researchers conceded it was a weak association. The correlation indicated the SBP-lowering effects of liraglutide involve some part of the weight-loss mechanism, but also raised the possibility of other mechanisms through which (GLP-1) agonists might modulate blood pressure, according to study co-author Dr. Jorge Plutzky,director of the Lipid/Prevention Clinic at Brigham and Women’s Hospital and an associate professor at Harvard Medical School in Boston.

The American Association of Clinical Endocrinologists recommends maintaining BP less than 120/75 mmHg to limit cardiovascular complications, but the study’s authors pointed out that doing so often requires multiple antihypertensive medications, lowers adherence, and increases risks of side effects and drug interactions — problems that are especially prevalent in patients with type 2 diabetes, who are often already on numerous drug therapies to manage the disease.

Between 20% and 60% of diabetics suffer hypertension, according to the study, and treating the condition by lowering blood pressure has proven effective in limiting cardiovascular complications and improving long-term outcomes.

“A major issue for patients with diabetes is their increased cardiovascular risk, so major attention has focused on the cardiovascular effects of anti-diabetic agents in the hopes that they might decrease cardiovascular risk or, at the very least, improve cardiovascular safety,” said Dr. Plutzky. “In patients with poorly controlled hypertension and diabetes, (GLP-1) agonists might offer some additional value to their glucose lowering effects, which is their indicated use.”

The lead author of this study, published Journal of Diabetes and Its Complications, has received both advisory board and speaker’s bureau honoraria from Novo Nordisk.

—Dan Cook

Reference:

1. Fonseca VA, DeVries JH, Henry RR, Donsmark M, Thomsen HF, Plutzky J. Reductions in systolic blood pressure with liraglutide in patients with type 2 diabetes: Insights from a patient-level pooled analysis of six randomized clinical trials. J Diabetes Complications. 2014;28(3):399-405.