Effect of bromocriptine-QR therapy on glycemic control in subjects with type 2 diabetes mellitus whose dysglycemia is inadequately controlled on insulin

Abstract

Objective: The concurrent use of an insulin sensitizer in type 2 diabetes mellitus (T2DM) patients with inadequate glycemic control on basal-bolus insulin may help improve glycemic control while limiting further insulin requirement. Bromocriptine-QR (B-QR), a quick release, sympatholytic, dopamine D2 receptor agonist therapy for T2DM, is a postprandial insulin sensitizer. This study evaluated the effect of B-QR on dysglycemia in T2DM subjects with suboptimal glycemic control on basal-bolus insulin plus metformin. Methods: The effect of once-daily morning administration of B-QR on dysglycemia was evaluated in 60 T2DM subjects derived from the Cycloset Safety Trial, with HbA1c >7% on basal-bolus insulin plus metformin at baseline, randomized to B-QR (N = 44) versus placebo (N = 16) and completed 12 weeks of study drug treatment. The analyses also included a subset of subjects on high-dose insulin (total daily insulin dose (TDID) ≥70 units; N = 36: 27 B-QR; 9 placebo). Results: Subjects were well matched at baseline. After 12 weeks of B-QR treatment, mean % HbA1c decreased by -0.73% relative to baseline (p < 0.001) and by -1.13 relative to placebo (p < 0.001). In the high-dose insulin subset, B-QR therapy resulted in % HbA1c reductions of -0.95 and -1.49 relative to baseline (p < 0.001) and placebo (p = 0.001) respectively. Secondary analyses of treatment effect at 24 and 52 weeks demonstrated similar influences of B-QR on HbA1c. The fasting plasma glucose (FPG) and TDID changes within each treatment group were not significant. More subjects achieved HbA1c ≤7 at 12 weeks with B-QR relative to placebo (36.4% B-QR vs 0% placebo, Fisher's exact 2-sided p = 0.003 in the entire cohort and 37% vs 0%, 2-sided p = 0.039 in the high-dose insulin subset). Conclusion: B-QR therapy improves glycemic control in T2DM subjects whose glycemia is poorly controlled on metformin plus basal-bolus insulin, including individuals on high-dose basal-bolus insulin. This glycemic impact occurred without significant change in FPG, suggesting a postprandial glucose lowering mechanism of action.Cycloset Safety Trial registration: ClinicalTrials.gov Identifier: NCT00377676 ARTICLE HISTORY

Neuroprotective strategies for retinal disease

“…It is not clear if L-DOPA treatments to the eye would require such large dosing. Finally, bromocriptine treatment in Type II diabetes has already been shown to improve glucose control (Chamarthi and Cincotta, 2017), increase fat loss (Meier et al, 1992), and prevent progression of kidney disease (Mejia Rodriguez et al, 2013), suggested that systemic disease might benefit with dopamine agonist treatment, in addition to potential retinal benefits.…”

Analysis of the Relationship between Type II Diabetes Mellitus and Parkinson’s Disease: A Systematic Review

“…A relationship between T2DM and L-dopa therapy [71, 73] and dopaminergic agonists, especially bromocriptine [74, 76, 77, 80–83], has been detected. In trials with rodents, L-dopa therapy caused a decrease in insulin secretion in glucose tolerance tests due to the dopamine increase in pancreatic cells [173].…”

The effect of dopamine agonists on metabolic variables in adults with type 2 diabetes: A systematic review with meta analysis and trial sequential analysis of randomized clinical trials

“…An additional two records were identified by searching the reference lists of included trials and reviews. As illustrated in the PRISMA flow diagram (Appendix S1), 28 17 publications [10][11][12][29][30][31][32][33][34][35][36][37][38][39][40][41][42] reporting the effect of bromocriptine or cabergoline on T2D in nine trials 11,12,[29][30][31]33,37,38,41 were identified. A total of 3456 participants were randomized and 3433 were included in the final analyses.…”