DPP4 (Dipeptidyl Peptidase-4) Inhibition Increases Catecholamines Without Increasing Blood Pressure During Sustained ACE (Angiotensin-Converting Enzyme) Inhibitor Treatment.
Hypertension
; 79(4): 827-835, 2022 04.
Article
em En
| MEDLINE
| ID: mdl-35045722
ABSTRACT
BACKGROUND:
DPP4 (dipeptidyl peptidase-4) inhibitors comprise a class of oral diabetes medication that have the potential for off-target cardiovascular effects. We previously showed that DPP4 inhibition attenuates the hypotensive effect of acute ACE (angiotensin-converting enzyme) inhibition and increases norepinephrine. Here, we investigated the effects of DPP4 during sustained ACE inhibition compared with during therapy with an ARB (angiotensin receptor blocker) or calcium channel blocker (neutral comparator) in a randomized, double-blinded crossover study.METHODS:
We enrolled 106 adults with type 2 diabetes and hypertension and 100 received intervention. Subjects were randomized to one of 3 blood pressure arms ramipril, valsartan, or amlodipine for a total of 15 weeks and received 3 one-week crossover therapies in random order placebo + placebo, sitagliptin + placebo, and sitagliptin + aprepitant separated by 4-week washout.RESULTS:
We found that DPP4 inhibition increased norepinephrine during ramipril but did not increase blood pressure. Aprepitant, a NK1 (substance P) receptor blocker, lowered standing heart rate during renin-angiotensin-aldosterone system blockade with ramipril or valsartan.CONCLUSIONS:
Increased catecholamines during concurrent ACE and DPP4 inhibition may contribute to cardiovascular complications in patients predisposed to heart failure.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fármacos Cardiovasculares
/
Diabetes Mellitus Tipo 2
Tipo de estudo:
Clinical_trials
Limite:
Adult
/
Humans
Idioma:
En
Revista:
Hypertension
Ano de publicação:
2022
Tipo de documento:
Article