Horm Metab Res 2015; 47(11): 805-812
DOI: 10.1055/s-0035-1559684
Review
© Georg Thieme Verlag KG Stuttgart · New York

Efficacy and Safety of Bromocriptine-QR in Type 2 Diabetes: A Systematic Review and Meta-Analysis

W. Liang*
1   Key Laboratory of Endocrinology of Ministry of Health, Department of Endocrinology, Peking Union Medical College Hospital, Peking Union Medical College, Beijing, China
,
L. Gao*
1   Key Laboratory of Endocrinology of Ministry of Health, Department of Endocrinology, Peking Union Medical College Hospital, Peking Union Medical College, Beijing, China
,
N. Li
1   Key Laboratory of Endocrinology of Ministry of Health, Department of Endocrinology, Peking Union Medical College Hospital, Peking Union Medical College, Beijing, China
,
B. Wang
2   School of Public Health, Peking Union Medical College, Beijing, China
,
L. Wang
1   Key Laboratory of Endocrinology of Ministry of Health, Department of Endocrinology, Peking Union Medical College Hospital, Peking Union Medical College, Beijing, China
,
Y. Wang
2   School of Public Health, Peking Union Medical College, Beijing, China
,
H. Yang
1   Key Laboratory of Endocrinology of Ministry of Health, Department of Endocrinology, Peking Union Medical College Hospital, Peking Union Medical College, Beijing, China
,
L. You
2   School of Public Health, Peking Union Medical College, Beijing, China
,
J. Hou
1   Key Laboratory of Endocrinology of Ministry of Health, Department of Endocrinology, Peking Union Medical College Hospital, Peking Union Medical College, Beijing, China
,
S. Chen
1   Key Laboratory of Endocrinology of Ministry of Health, Department of Endocrinology, Peking Union Medical College Hospital, Peking Union Medical College, Beijing, China
,
H. Zhu
1   Key Laboratory of Endocrinology of Ministry of Health, Department of Endocrinology, Peking Union Medical College Hospital, Peking Union Medical College, Beijing, China
,
Y. Jiang
2   School of Public Health, Peking Union Medical College, Beijing, China
,
H. Pan
1   Key Laboratory of Endocrinology of Ministry of Health, Department of Endocrinology, Peking Union Medical College Hospital, Peking Union Medical College, Beijing, China
› Author Affiliations
Further Information

Publication History

received 23 April 2015

accepted 21 July 2015

Publication Date:
02 September 2015 (online)

Abstract

Bromocriptine-QR (quick release) is a novel treatment for type 2 diabetes. The objective of this study is to assess the efficacy and safety of bromocriptine-QR in adults with type 2 diabetes mellitus based on randomized controlled trials published in peer-reviewed journals or as abstracts. We performed a comprehensive literature search of MEDLINE, Pubmed, Web of Science, EMBASE, and the Cochrane Library up to May 2015. Randomized controlled trials of bromocriptine-QR therapy in type 2 diabetes mellitus were eligible. Two reviewers independently assessed the eligibility of trials based on predefined inclusion criteria. Information was collected concerning basic study data, patient characteristics, efficacy and safety outcomes, and methodological quality. Bromocriptine-QR add-on therapy lowered hemoglobin A1c compared with placebo (weighted mean difference, − 6.52 mmol/mol; 95% CI, − 8.07 to − 4.97 mmol/mol). Bromocriptine-QR exhibited an increase in achieving an HbA1c level≤53 mmol/mol (≤ 7.0%) (32.0 vs. 9.5%; odds ratio, 4.57; 95% CI, 2.42–8.62). Fasting plasma glucose was reduced with bromocriptine-QR compared with placebo (weighted mean difference,−1.04 mmol/l; 95% CI,−1.49 to−0.59 mmol/l). Moreover, bromocriptine-QR had neutral effects on postprandial glycemia, Body Mass Index (BMI), and lipid profile. Bromocriptine-QR had more gastrointestinal side effects of nausea and vomiting. Bromocriptine-QR had no increased risk of hypoglycemia, hypotension, or cardiovascular effects. Bromocriptine-QR therapy offers an alternative option to currently available antidiabetic agents for type 2 diabetes mellitus adults. Neither hypoglycemia nor other metabolic changes occur with this drug. More data for long-term efficacy and safety are needed for further observation.

* These 2 authors contributed equally to this work and should be considered as first co-authors


Supporting Information

 
  • References

  • 1 Meier AH, Cincotta AH. Circadian rhythms regulate the expression of the thrifty genotype/phenotype. Diabetes Rev 1996; 4: 464-487
  • 2 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
  • 3 Kalra S, Kalra B, Agrawal N, Kumar S. Dopamine: The Forgotten Felon in Type 2 Diabetes. Rec Pat Endocr Metab Immune Drug Discov 2011; 5: 61-65
  • 4 Luo S, Luo J, Cincotta AH. Chronic ventromedial hypothalamic infusion of norepinephrine and serotonin promotes insulin resistance and glucose intolerance. Neuroendocrinology 1999; 70: 460-465
  • 5 Reynolds GP, Kirk SL. Metabolic side effects of antipsychotic drug treatment–pharmacological mechanisms. Pharmacol Therap 2010; 125: 169-179
  • 6 García-Tornadú I, Ornstein AM, Chamson-Reig A, Wheeler MB, Hill DJ, Arany E, Rubinstein M, Becu-Villalobos D. Disruption of the dopamine d2 receptor impairs insulin secretion and causes glucose intolerance. Endocrinology 2010; 151: 1441-1450
  • 7 Defronzo RA. Bromocriptine: a sympatholytic, d2-dopamine agonist for the treatment of type 2 diabetes. Diabetes Care 2011; 34: 789-794
  • 8 Schwartz SL. Bromocriptine (Ergoset (R)) improves glycemic control in type 2 diabetics on insulin. Diabetes 1999; 48: A99-A99
  • 9 Ezrokhi M, Luo S, Cincotta J, Cincotta AH. Timed dopamine agonist therapy induces a postprandial-selective insulin sensitivity. Diabetologia 2008; 51: S276-S276
  • 10 Bell DS. Focusing on cardiovascular disease in type 2 diabetes mellitus: an introduction to bromocriptine QR. Postgrad Med 2012; 124: 121-135
  • 11 Via MA, Chandra H, Araki T, Potenza MV, Skamagas M. Bromocriptine approved as the first medication to target dopamine activity to improve glycemic control in patients with type 2 diabetes. Diabetes Metab Syndrome Obes 2010; 3: 43-48
  • 12 Moher D, Liberati A, Tetzlaff J, Altman DG. Group P . Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. J Clin Epidemiol 2009; 62: 1006-1012
  • 13 Goldstein DE, Little RR, Lorenz RA, Malone JI, Nathan D, Peterson CM, Sacks DB. Tests of glycemia in diabetes. Diabetes Care 2004; 27: 1761-1773
  • 14 DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials 1986; 7: 177-188
  • 15 Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Statistics Med 2002; 21: 1539-1558
  • 16 Ghosh A, Sengupta N, Sahana P, Giri D, Sengupta P, Das N. Efficacy and safety of add on therapy of bromocriptine with metformin in Indian patients with type 2 diabetes mellitus: a randomized open labeled phase IV clinical trial. Indian J Pharmacol 2014; 46: 24-28
  • 17 Vinik AI, Cincotta AH, Scranton RE, Bohannon N, Ezrokhi M, Gaziano JM. 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
  • 18 Ramteke KB, Ramanand SJ, Ramanand JB, Jain SS, Raparti GT, Patwardhan MH, Murthy M, Ghanghas RG. Evaluation of the efficacy and safety of bromocriptine QR in type 2 diabetes. Indian J Endocrinol Metab 2011; 15: S33-S39
  • 19 Florez H, Scranton R, Farwell WR, DeFronzo RA, Ezrokhi M, Gaziano JM, Cincotta AH. Randomized clinical trial assessing the efficacy and safety of bromocriptine-QR when added to ongoing thiazolidinedione therapy in patients with type 2 diabetes mellitus. J. Diabetes Metab 2011; 2: 142
  • 20 Pijl H, Ohashi S, Matsuda M, Miyazaki Y, Mahankali A, Kumar V, Pipek R, Iozzo P, Lancaster JL, Cincotta AH, DeFronzo RA. Bromocriptine: a novel approach to the treatment of type 2 diabetes. Diabetes Care 2000; 23: 1154-1161
  • 21 Cincotta AH, Meier AH, Cincotta Jr M. Bromocriptine improves glycaemic 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
  • 22 Scranton R, Erzoki M, Farwell W, Gaziano JM, Cincotta A. Quick release bromocriptine (Cycloset™) a novel treatment for type 2 diabetes also demonstrates improvements in blood pressure. Canad J Diabetes 2009; 33: 235
  • 23 Gaziano JM, Cincotta AH, Vinik A, Blonde L, Bohannon N, Scranton R. 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
  • 24 Gaziano JM, Cincotta AH, O’Connor CM, Ezrokhi M, Rutty D, Ma ZJ, Scranton RE. 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
  • 25 Bell DS. Why does quick-release bromocriptine decrease cardiac events?. Diabetes Obes Metab 2011; 13: 880-884
  • 26 Luo SQ, 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
  • 27 Rubi B, Ljubicic S, Pournourmohammadi S, Carobbio S, Armanet M, Bartley C, Maechler P. Dopamine D2-like receptors are expressed in pancreatic beta cells and mediate inhibition of insulin secretion. J Biol Chem 2005; 280: 36824-36832
  • 28 Maffei A, Segal AM, Alvarez-Perez JC, Garcia-Ocana A, Harris PE. Anti-incretin, Anti-proliferative Action of Dopamine on beta-Cells. Mol Endocrinol 2015; 29: 542-557
  • 29 Roe ED, Chamarthi B, Raskin P. Impact of Bromocriptine-QR Therapy on Glycemic Control and Daily Insulin Requirement in Type 2 Diabetes Mellitus Subjects Whose Dysglycemia Is Poorly Controlled on High-Dose Insulin: A Pilot Study. J Diabetes Res 2015; 2015: 7
  • 30 Ezrokhi M, Luo S, Trubitsyna Y, Cincotta AH. Weighted effects of bromocriptine treatment on glucose homeostasis during hyperglycemic vs. euglycemic clamp conditions in insulin resistant hamsters: bromocriptine as a unique postprandial insulin sensitizer. J Diabetes Metab 2012; S2 DOI: 10.4172/2155-6156.s2-007.
  • 31 Ezrokhi M, Luo S, Trubitsyna Y, Cincotta AH. Neuroendocrine and metabolic components of dopamine agonist amelioration of metabolic syndrome in SHR rats. Diabetol Metab Syndr 2014; 6 104: 10.1186/1758-5996-1186-1104. eCollection 2014
  • 32 Kamath V, Jones CN, Yip JC, Varasteh BB, Cincotta AH, Reaven GM, Chen YD. Effects of a quick-release form of bromocriptine (Ergoset) on fasting and postprandial plasma glucose, insulin, lipid, and lipoprotein concentrations in obese nondiabetic hyperinsulinemic women. Diabetes Care 1997; 20: 1697-1701
  • 33 Bloomgarden ZT, Einhorn D. Hypoglycemia in type 2 diabetes: current controversies and changing practices. Front Endocrinol 2012; 3
  • 34 Goetz CG, Poewe W, Rascol O, Sampaio C. Evidence-based medical review update: pharmacological and surgical treatments of Parkinson’s disease: 2001 to 2004. Mov Disord 2005; 20: 523-539
  • 35 Korczyn AD, Brooks DJ, Brunt ER, Poewe WH, Rascol O, Stocchi F. Ropinirole versus bromocriptine in the treatment of early Parkinson’s disease: A 6-month interim report of a 3-year study. Movement Disord 1998; 13: 46-51
  • 36 Mizuno Y, Yanagisawa N, Kuno S, Yamamoto M, Hasegawa K, Origasa H, Kowa H. Japanese Pramipexole Study G . Randomized, double-blind study of pramipexole with placebo and bromocriptine in advanced Parkinson’s disease. Mov Disord 2003; 18: 1149-1156
  • 37 Danaei G, Finucane MM, Lu Y, Singh GM, Cowan MJ, Paciorek CJ, Lin JK, Farzadfar F, Khang Y-H, Stevens GA. National, regional, and global trends in fasting plasma glucose and diabetes prevalence since 1980: systematic analysis of health examination surveys and epidemiological studies with 370 country-years and 2· 7 million participants. Lancet 2011; 378: 31-40
  • 38 Kaye SB, Shaw KM, Ross EJ. Letter: Bromocriptine and hypertension. Lancet 1976; 1: 1176-1177
  • 39 Lokhandwala MF, Tadepalli AS, Jandhyala BS. Cardiovascular actions of bromocriptine: evidence for a neurogenic mechanism. J Pharmacol Exp Therap 1979; 211: 620-625
  • 40 McDonald MD, Daniel E, Lam MD, Raymond W. Domperidone for Drug-Induced Orthostatic Hypotension – A Review. Jefferson J Psychiatry 2011; 10: 5
  • 41 Senard JM, Rai S, Lapeyre-Mestre M, Brefel C, Rascol O, Rascol A, Montastruc JL. Prevalence of orthostatic hypotension in Parkinson’s disease. J Neurol Neurosurg Psychiatry 1997; 63: 584-589
  • 42 Andersohn F, Garbe E. Cardiac and noncardiac fibrotic reactions caused by ergot-and nonergot-derived dopamine agonists. Mov Disord 2009; 24: 129-133
  • 43 Antonini A, Poewe W. Fibrotic heart-valve reactions to dopamine-agonist treatment in Parkinson’s disease. Lancet Neurol 2007; 6: 826-829
  • 44 Kim JY, Chung EJ, Park SW, Lee WY. Valvular heart disease in Parkinson’s disease treated with ergot derivative dopamine agonists. Mov Disord 2006; 21: 1261-1264
  • 45 Tan LC, Ng KK, Au WL, Lee RK, Chan YH, Tan NC. Bromocriptine use and the risk of valvular heart disease. Mov Disord 2009; 24: 344-349
  • 46 Halperin I, Aller J, Varela C, Mora M, Abad A, Doltra A, Santos AE, Batista E, García-Pavía P, Sitges M, Mirelis JG, Lucas T, Puig-Domingo M. No clinically significant valvular regurgitation in long-term cabergoline treatment for prolactinoma. Clin Endocrinol 2012; 77: 275-280
  • 47 Elenkova A, Shabani R, Kalinov K, Zacharieva S. Increased prevalence of subclinical cardiac valve fibrosis in patients with prolactinomas on long-term bromocriptine and cabergoline treatment. Eur J Endocrinol 2012; 167: 17-25
  • 48 Boguszewski CL, dos Santos CM, Sakamoto KS, Marini LC, de Souza AM, Azevedo M. A comparison of cabergoline and bromocriptine on the risk of valvular heart disease in patients with prolactinomas. Pituitary 2012; 15: 44-49
  • 49 Drake WM, Stiles CE, Howlett TA, Toogood AA, Bevan JS, Steeds RP. UK Dopamine Agonist Valvulopathy Group . A cross-sectional study of the prevalence of cardiac valvular abnormalities in hyperprolactinemic patients treated with ergot-derived dopamine agonists. J Clin Endocrinol Metab 2014; 99: 90-96