Bromocriptine appears to drop BP, improve arterial stiffness in teens with type 1 diabetes
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Bromocriptine, a drug previously used to treat adults with type 2 diabetes and Parkinson’s disease, improved BP and central and peripheral aortic stiffness over 4 weeks in adolescents with type 1 diabetes, researchers reported.
“We know that abnormalities in the large vessels around the heart, the aorta and its primary branches begin to develop in early childhood in people with type 1 diabetes,” Michal Schäfer, PhD, researcher and fourth-year medical student at the University of Colorado School of Medicine in Aurora, said in a press release. “We found that bromocriptine has the potential to slow down the development of those abnormalities and decrease the risk for cardiovascular disease in this population.”
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The results of the bromocriptine quick-release type 1 diabetes (BCQR-T1D) study were published in Hypertension.
Bromocriptine’s previous indications
Bromocriptine (Cycloset) is an exogenous sympatholytic D2-dopamine agonist that improves glucose tolerance and insulin sensitivity, according to the study. A quick-release formulation was developed to enhance central nervous system dopaminergic activity and is used to treat adults with type 2 diabetes as well as treat Parkinson’s disease.
Bromocriptine for type 1 diabetes
The BCQR-T1D trial was a placebo-controlled, random-order, double-blind, crossover study that evaluated the effect of bromocriptine 0.8 mg compared with placebo on vascular function in 34 adolescents with type 1 diabetes (mean age, 16 years; mean HbA1c, 8.6%; median type 1 diabetes duration, 6 years).
Participants were assigned to bromocriptine or placebo for 4 weeks in phase 1, followed by a 4-week washout period and then a 4-week phase 2 with the alternate treatment. Participants were uptitrated each week if the treatment was tolerated, according to the study. If uptitration up to 1.6 mg was not tolerated, the patient was withdrawn from the trial.
Upon the completion of each phase of the study, participants underwent CV MRI, pressure hemodynamics and peripheral vascular evaluation.
Compared with placebo, bromocriptine therapy for adolescents with type 1 diabetes:
- decreased systolic BP (mean difference, 5 mm Hg; 95% CI, 3 to 7; P < .001);
- decreased diastolic BP (mean difference, 2 mm Hg; 95% CI, 4 to 0; P = .039);
- reduced ascending aortic pulse wave velocity (mean change, 0.4 m per second; P = .018);
- increased relative area change (mean change, 2.6%; P = .083); and
- increased distensibility (mean change, 0.08% mm Hg; P = .017).
Moreover, in the thoracoabdominal aorta, bromocriptine decreased pulse wave velocity (mean change, 0.2 m per second; P = .007) and increased distensibility (mean change, 0.05% per mm Hg; P = .013) compared with placebo.
“A stiff aorta predisposes a patient to other health issues, such as organ dysfunction or atherosclerosis and higher stress or strain on cardiac muscle,” Schäfer said in the release. “We were able to take it a notch further and show, using more sophisticated metrics, that these central large arteries are impaired, and impairment among adolescents and young adults with type 1 diabetes may be decelerated with this drug.”
Reference:
- Parkinson’s medication improved blood pressure in teens with type 1 diabetes. newsroom.heart.org/news/parkinsons-medication-improved-blood-pressure-in-teens-with-type-1-diabetes. Published Dec. 6, 2022. Accessed Dec. 6, 2022.
Perspective
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This is a very interesting study focusing on an area of increasing importance. Type 1 diabetes is strongly associated with poor CV outcomes and intervening early may be key to optimizing CV risk and preventing events. This study evaluates the effect of bromocriptine in a primarily adolescent population with type 1 diabetes and found significant difference in BP and vascular mechanics compared with placebo. It was a shorter duration study with a small sample size, but the results certainly justify future evaluation of long-term outcomes of bromocriptine.
I am not entirely surprised by the results, as the physiology in reducing aortic stiffness is clear given the reduced sympathetic function. I am interested to see if there are long-term effects in reducing CV outcomes with changes in aortic stiffness at an earlier age. Additionally, how different are the changes in outcomes compared with those with type 2 diabetes.
We certainly will need longer-term data to assess if starting these therapies sooner have any safety concerns. Additionally, larger sample sizes will also help determine safety. It is nice that the investigators allowed for a dose titration to make sure the drug was tolerable to participants. That is likely to happen in more real-world settings.
This appears to be a promising intervention and more longer-term data will be helpful to see if there are truly impacts in reducing CV events. The pathophysiology is also interesting, as there were regional differences in aortic stiffness between metformin (EMERALD trial) and bromocriptine. This certainly needs to be explored more as to why the differences exist and does it have implications on who would benefit from one therapy vs. the other.
Furthermore, more subgroup analyses will be interesting, as there were some differences across BMI with bromocriptine. It will be important to understand which population will benefit most from the therapy to best determine timing of intervention and allocation.
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