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Cited by 25Diabetes Treatment and ManagementDiabetes Management and ResearchDiabetes, Cardiovascular Risks, and Lipoproteins

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

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Chamarthi, Bindu, Cincotta, Anthony H.·2017·Postgraduate Medicine
DOI 10.1080/00325481.2017.1315290
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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.

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References 53 · Cited by 25

Research works printed but not linked: 43

  1. UK Hypoglycaemia Study Group. Risk of hypoglycaemia in types 1 and 2 diabetes: effects of treatment modalities and their duration. Diabetologia. 2007;50:1140-1147.
  2. Pontiroli AE, Miele L, Morabito A. Increase of body weight during the first year of intensive insulin treatment in type 2 diabetes: systematic review and meta-analysis. Diabetes Obes Metab. 2011;13:1008-1019.
  3. Russell-Jones D, Khan R. Insulin-associated weight gain in dia- betes-causes, effects and coping strategies. Diabetes Obes Metab. 2007;9:799-812.
  4. Yki-Järvinen H. Thiazolidinediones. N Engl J Med. 2004;351:1106- 1118.
  5. Chaggar PS, Shaw SM, Williams SG. Review article: thiazolidine- diones and heart failure. Diab Vasc Dis Res. 2009;6:146-152.
  6. Horita S, Nakamura M, Satoh N, et al. Thiazolidinediones and edema: recent advances in the pathogenesis of thiazolidine- diones-induced renal sodium retention. PPAR Res. 2015;2015:1-7.
  7. Aubert RE, Herrera V, Chen W, et al. Rosiglitazone and pioglitazone increase fracture risk in women and men with type 2 diabetes. Diabetes Obes Metab. 2010;12:716-721.
  8. Billington EO, Grey A, Bolland MJ. The effect of thiazolidinediones on bone mineral density and bone turnover: systematic review and meta-analysis. Diabetologia. 2015;58:2238-2246.
  9. Clar C, Royle P, Waugh N. Adding pioglitazone to insulin containing regimens in type 2 diabetes: systematic review and meta-analysis. PLoS One. 2009;4:e6112.
  10. Scheen AJ. Combined thiazolidinedione-insulin therapy: should we be concerned about safety? Drug Saf. 2004;27:841-856.
  11. Gaziano JM, Cincotta AH, O'Connor CM, et al. Randomized clinical trial of quick-release bromocriptine among patients with type 2 diabetes on overall safety and cardiovascular outcomes. Diabetes Care. 2010;33:1503-1508.
  12. Gaziano JM, Cincotta AH, Vinik A, et al. Effect of bromocriptine-QR (a quick-release formulation of bromocriptine mesylate) on major adverse cardiovascular events in type 2 diabetes subjects. J Am Heart Assoc. 2012;1:e002279.
  13. Vinik AI, Cincotta AH, Scranton RE, et al. Effect of bromocriptine-QR on glycemic control in subjects with uncontrolled hyperglycemia on one or two oral anti-diabetes agents. Endocr Pract. 2012;18:931-943.
  14. Defronzo RA. Bromocriptine: a sympatholytic, d2-dopamine agonist for the treatment of type 2 diabetes. Diabetes Care. 2011;34:789- 794.
  15. Pijl H, Ohashi S, Matsuda M, et al. Bromocriptine: a novel approach to the treatment of type 2 diabetes. Diabetes Care. 2000;23:1154- 1161.
  16. Cincotta AH, Meier AH, Cincotta JM. Bromocriptine improves gly- caemic control and serum lipid profile in obese Type 2 diabetic subjects: a new approach in the treatment of diabetes. Expert Opin Investig Drugs. 1999;8:1683-1707.
  17. Scranton R, Cincotta A. Bromocriptine-unique formulation of a dopamine agonist for the treatment of type 2 diabetes. Expert Opin Pharmacother. 2010;11:269-279.
  18. Monti JM, Monti D. The involvement of dopamine in the modula- tion of sleep and waking. Sleep Med Rev. 2007;11:113-133.
  19. Raskin P, Cincotta AH. Bromocriptine-QR therapy for the manage- ment of type 2 diabetes mellitus: developmental basis and ther- apeutic profile summary. Expert Rev Endocrinol Metab. 2016;11:113-148.
  20. Ezrokhi M, Luo S, Trubitsyna Y, et al. Neuroendocrine and meta- bolic components of dopamine agonist amelioration of metabolic syndrome in SHR rats. Diabetol Metab Syndr. 2014;6:104.
  21. Cincotta AH, MacEachern TA, Meier AH. Bromocriptine redirects metabolism and prevents seasonal onset of obese hyperinsuline- mic state in Syrian hamsters. Am J Physiol. 1993;264:E285-93.
  22. Bina KG, Cincotta AH. Dopaminergic agonists normalize elevated hypothalamic neuropeptide Y and corticotropin-releasing hor- mone, body weight gain, and hyperglycemia in ob/ob mice. Neuroendocrinology. 2000;71:68-78.
  23. Luo S, Meier AH, Cincotta AH. Bromocriptine reduces obesity, glucose intolerance and extracellular monoamine metabolite levels in the ventromedial hypothalamus of Syrian hamsters. Neuroendocrinology. 1998;68:1-10.
  24. Luo S, Luo J, Meier A. Dopaminergic neurotoxin administration to the area of the suprachiasmatic nuclei induces insulin resistance. Neuroreport. 1997;8:3495-3499.
  25. Luo S, Luo J, Cincotta AH. Suprachiasmatic nuclei monoamine metabolism of glucose tolerant versus intolerant hamsters. NeuroReport. 1999;10:2073-2077.
  26. Cincotta AH, Meier AH. Bromocriptine (Ergoset) reduces body weight and improves glucose tolerance in obese subjects. Diabetes Care. 1996;19:667-670.
  27. Roe ED, Chamarthi B, Raskin P. Impact of bromocriptine-QR therapy on glycemic control and daily insulin requirement in type 2 dia- betes mellitus subjects whose dysglycemia is poorly controlled on high-dose insulin: a pilot study. J Diabetes Res. 2015;2015:834903.
  28. Florez H, Scranton R, Farwell WR, et al. Randomized clinical trial assessing the efficacy and safety of bromocriptine-qr when added to ongoing thiazolidinedione therapy in patients with type 2 dia- betes mellitus. J Diabetes Metab. 2011;2:142.
  29. Cincotta AH, Luo S, Zhang Y, et al. Chronic infusion of norepinephrine into the VMH of normal rats induces the obese glucose-intolerant state. Am J Physiol Regulatory Integrative Comp. Physiol. 2000;278:R435-44.
  30. Luo S, Luo J, Cincotta AH. Chronic ventromedial hypothalamic infu- sion of norepinephrine and serotonin promotes insulin resistance and glucose intolerance. Neuroendocrinology. 1999;70:460-465.
  31. Zheng H, Liu X, Li Y, et al. Attenuated dopaminergic tone in the paraventricular nucleus contributing to sympathoexcitation in rats with Type 2 diabetes. Am J Physiol Regul Integr Comp Physiol. 2014;306:R138-48.
  32. Tentolouris N, Liatis S, Katsilambros N. Sympathetic system activity in obesity and metabolic syndrome. Ann N Y Acad Sci. 2006;1083:129-152.
  33. Lambert GW, Straznicky NE, Lambert EA, et al. Sympathetic nervous activation in obesity and the metabolic syndrome-causes, conse- quences and therapeutic implications. Pharmacol Ther. 2010;126:159-172.
  34. Chiodini I, Adda G, Scillitani A. Cortisol secretion in patients with type 2 diabetes: relationship with chronic complications. Diabetes Care. 2007;30:83-88.
  35. Jordan SD, Könner AC, Brüning JC. Sensing the fuels: glucose and lipid signaling in the CNS controlling energy homeostasis. Cell Mol Life Sci. 2010;67:3255-3273.
  36. Raskin P. Why insulin sensitizers but not secretagogues should be retained when initiating insulin in type 2 diabetes. Diabetes Metab Res Rev. 2008;24:3-13.
  37. Bell DSH. Focusing on cardiovascular disease in type 2 diabetes mellitus: an introduction to bromocriptine-QR. Postgradmed. 2012;124:121-135.
  38. Cersosimo E, DeFronzo RA. Insulin resistance and endothelial dys- function: the road map to cardiovascular diseases. Diabetes Metab Res Rev. 2006;22:423-436.
  39. Jia G, DeMarco VG, Sowers JR. Insulin resistance and hyperinsuli- naemia in diabetic cardiomyopathy. Nat Rev Endocrinol. 2016;12:144-153.
  40. O'Keefe JH, Bell DS. Postprandial hyperglycemia/hyperlipidemia (postprandial dysmetabolism) is a cardiovascular risk factor. Am J Cardiol. 2007;100:899-904.
  41. Garber AJ. Postprandial dysmetabolism and the heart. Heart Fail Clin. 2012;8:563-573.
  42. Node K, Inoue T. Postprandial hyperglycemia as an etiological factor in vascular failure. Cardiovasc Diabetol. 2009;8:23.
  43. Grassi G. Sympathetic overdrive and cardiovascular risk in the metabolic syndrome. Hypertens Res. 2006;29:839-847.

Authors
Chamarthi, B., & Cincotta, A. H.
Affiliations
  • Brigham and Women's Hospital (US)
  • Veroscience (United States) (US)
Corresponding author
Chamarthi, Bindu
ORCID
Venue
Postgraduate Medicine
Publisher
Informa UK Limited
Published
2017-04-12
Volume
129
Issue
4
Pages
446-455
ISSN
  • 0032-5481 (ISSN-L)
  • 1941-9260
DOI
10.1080/00325481.2017.1315290
OpenAlex
W2605067301
Cited by
25
References
53
Citations by year
2025: 1 · 2024: 2 · 2023: 6 · 2022: 4 · 2021: 1 · 2020: 4 · 2019: 1 · 2018: 5 · 2017: 1
FWCI
2.38
Type
journal article
Language
en
Open access
Locations
  • Postgraduate Medicine (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • S2 Therapeutics
  • VeroScience, LLC
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
Keywords
bromocriptine, type 2 diabetes, glycemic control, multiple daily insulin injections, insulin requirement, HbA1c, insulin sensitizers, dopamine D2 receptor agonist, metformin, high-dose insulin, fasting blood glucose, postprandial insulin secretion, sympatholytic therapy, treatment-emergent adverse events
MeSH terms
Adult, Aged, Aged, 80 and over, Bromocriptine, Diabetes Mellitus, Type 2, Double-Blind Method, Drug Therapy, Combination, Female, Humans, Hypoglycemic Agents, Insulin, Insulin Resistance, Male, Metformin, Middle Aged, Treatment Outcome, Dopamine Agonists

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