Role of betahistine in glycemic control of obese subjects: a placebo- controlled clinical trial

Authors

  • Hayder H. Al-Anbari Department of Pharmacy, Al-Safwa University College, Karbalaa-Iraq
  • Ahmed S. Sahib Department of Pharmacology, University of Karbalaa, College of Pharmacy, Karbalaa-Iraq
  • Amer O. Al-Mukhtar Department of Medicine, University of Karbalaa, College of Medicine, Karbalaa-Iraq

DOI:

https://doi.org/10.18203/2319-2003.ijbcp20164774

Keywords:

Betahistine, Glycemic control, Insulin resistance, Lifestyle change, Obesity

Abstract

Background: Poor glycemic control, insulin resistance and abnormal beta cell function are of the most important complications that associated with obesity, targeting of such complications with pharmacological agents depending on the already existing central mechanism may decrease the incidence of morbidity and mortality among obese subjects. Betahistine is an anti-vertigo drug, commonly prescribed to patients with balance disorders or to improve vertigo symptoms associated with Meniere's disease. The aim of this study was to investigate the effect of betahistine on glycemic status, insulin resistance and pancreatic function in obese subjects.

Methods: A randomized, placebo controlled trial was carried out on 72 obese subjecta of both sexes with age range of 18-50 years who allocated into two groups: Group A: 48 patients treated with 144mg /day in three divided every eight hours for twelve weeks. Group B: 24 patients treated with placebo for twelve weeks to serve as control. For each group, demographic data, liver and renal function tests beside the studied parameters were investigated at baseline and after 12 weeks.

Results: Administration of betahistine to obese subjects resulted in improvement in fasting blood glucose, glycosylated hemoglobin, insulin resistance and beta cell percent values after twelve weeks compared to baseline values and placebo treated group.

Conclusions: Administration of betahistine in a dose of 144mg /day for twelve weeks to obese subjects effectively improve glycemic control, insulin resistance and beta cell functions in these subjects, indicating the beneficial effect of betahistine in slowing or reversing the long term progress of obesity complications without incidence of any serious adverse effects, indicating its efficacy and safety.

References

WHO definition for Obesity and overweight, facts sheet No 311, 2008, WHO definition for Obesity and overweight, facts sheet No 311, 2008, Updated January 2015.

Klop B, Elte JWF, Cabezas CM. Dyslipidemia in Obesity: Mechanisms and Potential Targets. Nutrients. 2013;5(4):1218-40.

Finucane MM, Stevens GA, Cowan MJ, Danaei G, Lin JK, Paciorek CJ, et al. National, regional, and global trends in body-mass index since 1980: systematic analysis of health examination surveys and epidemiological studies with 960 country-years and 9.1 million participants. Lancet. 2011;377:557-67.

WHO Global Health Observatory (GHO). Overweight and obesity. [Updated: 04/Apr/2011; cited: 28/May/2013]. From: http://www.who.int/gho/ncd /risk factors /overweight/en/index.html.

Musaiger AO, Al-Hazzaa HM. Prevalence and risk factors associated with nutrition-related noncommunicable diseases in the Eastern Mediterranean region, International Journal of General Medicine. 2012:5:199-217.

WHO 2005. WHO Global Infobase Indicators. Available at: https:// apps.who.int/infobase/Indicators.aspx.

Al-Hilaly KA, Aboud HA, Al-Ghabban SI. Prevalence of Obesity among Adult Population in Karbala. Kufa Medical Journal. 2008;11(1):326-34.

Al-Ghabban SI. Prevalence of Overweight and Obesity among Students in University of Kerbala, Medical Journal of Babylon. 2013;10:205-18.

Grundy SM. Multifactorial causation of obesity: implications for prevention. Am J Clin Nutr. 1998;67:563S-72S.

Brownell KD, Frieden TR. Ounces of prevention-The public policy case for taxes on sugared beverages. N Engl J Med. 2009;360:1805-8.

Colditz GA, Willett WC, Rotnitzky A, Manson JE. Weight gain as a risk factor for clinical diabetes mellitus in women. Ann Intern Med. 1995;122:481-6.

Chan JM, Rimm EB, Colditz GA, Stampfer MJ, Willett WC. Obesity and fat distribution and weight gain as risk factors for clinical diabetes in men. Diabetes Care. 1994;17:961-9.

Nguyen NT, Nguyen XM, Lane J, Wang P. Relationship between obesity and diabetes in a US adult population: findings from the National Health and Nutrition Examination Survey, 1999-2006. Obes Surg. 2011;21(3):351-5.

Idelevich E, Kirch W, Schindler C. Current pharmacotherapeutic concepts for the treatment of obesity in adults. Ther Adv Cardiovasc Dis. 2009;3:75-90.

Kanders BS, Blackburn GL, Lavin P, Norton D. Weight loss outcome and health benefits associated with the Optifast program in the treatment of obesity. Int J Obes. 1989;13(2):131-4.

Black PH. The inflammatory consequences of psychologic stress: relationship to insulin resistance, obesity, atheroscle-rosis and diabetes mellitus, type II. Med Hypotheses. 2006;67:879-91.

Yanovski SZ, Bain RP, Williamson DF. Report of a National Institutes of Health-Centers for Disease Control and Prevention workshop on the feasibility of conducting a randomized clinical trial to estimate the long-term health effects of intentional weight loss in obese persons. Am J Clin Nutr. 1999;69:366-72.

Wing RR, Lang W, Wadden TA, Safford M, Knowler WC, Bertoni AG, et al. Look AHEAD Research Group. Benefits of modest weight loss in improving cardiovascular risk factors in overweight and obese individuals with type 2 diabetes. Diabetes Care. 2011;34(7):1481-6.

Sakata T, Yoshimatsu H, Kurokawa M. Hypothalamic neuronal histamine: implications of its homeostatic control of energy metabolism. Nutrition. 1997;13:403-11.

Passani MB, Blandina P, Torrealba F. The histamine H3 receptor and eating behavior. J Pharmacol Exp Ther. 2011;336(1):24-9.

Deng C, Weston-Green K, Huang XF. The role of histaminergic H 1 and H 3 receptors in food intake: a mechanism for atypical antipsychoticinduced weight gain? Prog Neuropsychopharmacol Biol Psychiatry. 2010;34:1-4.

Masaki T, Yoshimatsu H, Chiba S, Watanabe T, Sakata T. Central infusion of histamine reduces fat accumulation and upregulates UCP family in leptinresistant obese mice. Diabetes. 2001;50:376-84.

Lett TAP, Wallace TJM, Chowdhury NI. Pharmacogenetics of antipsychotic-induced weight gain: review and clinical implications. Mol Psychiatry. 2012;17(3):242-66.

Masaki T, Chiba S, Yasuda T, Noguchi H, Kakuma T, Watanabe T, et al. Involvement of hypothalamic histamine H1 receptor in the regulation of feeding rhythm and obesity. Diabetes. 2004;53(9):2250-60.

Hancock AA, Brune ME. Assessment of pharmacology and potential anti-obesity properties of H3 receptor antagonists/inverse agonists. Expert Opin. Investig. Drugs. 2005;14:223-41.

Esbenshade TA, Fox GB, Cowart MD. Histamine H3 receptor antagonists, preclinical promise for treating obesity and cognitive disorders, Molecular Interventions. 2006;6:77-88.

Provensi G, Blandina P, Passani MB. The histaminergic system as a target for the prevention of obesity and metabolic syndrome. Neuropharmacology. 2016;106:3-12.

Botta L, Mira E, Valli S, Zucca G, Perin P, Benvenuti C, et al. Effects of betahistine and of its metabolites on vestibular sensory organs. Acta Otorhinolaryngol Ital 2001;21(66):24-30.

NHLBI Obesity Education Initiative Expert Panel on the Identification, Evaluation, and Treatment of Obesity in Adults (US). Clinical Guidelines on the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults: The Evidence Report. Bethesda (MD): National Heart, Lung, and Blood Institute; 1998 Sep.

Dietary Guidelines for Americans, Department of Agriculture (USDA) and the Department of Health and Human Services (HHS). 2010.

Henry JB. Clinical Diagnosis and Management by Laboratory Methods, Volume 1, W.B Saunders Company, Philadelphia; 1979:60.

Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985;28(7):412-9.

Alan HH, Wu B. Tietz Clinical Guide to Laboratory Tests Fourth Edition. 2006.

Little RR. Glycated Hemoglobin Standardization- National Glycohemoglobin Standardization Program (NGSP) perspective, Clin. Chem. Lab. Med. 2003;41:1191-8.

Deneke U, Rittersdorf W, Werner W. Performance data of Reflotron-GOT (AST) dry chemistry test for Reflotron. Clin. Chem. 1985;31:921.

Carstensen CA, Nagel R, Knoll E, Wisser H, Weidemann G, Riesen WF, et al. Development and evaluation of a reagent carrier with a new reaction sequence for the determination of creatinine in blood, plasma, serum and urine. Eur J Clin Chem Clin Biochem. 1993;31(5):335-46.

NKF-KDOQI Clinical Practice Guidelines for Anemia of Chronic Kidney Disease: Update 2000. Am J Kidney Disease. 2001;77:S182-288.

Beischer W. Proinsulin and C-Peptide in Humans. Hormones in Normal and Abnormal Human Tissues. Volume 3K, Fotherby and Pal, S., ed. (Berlin: Walter DeGruyter); 1983:1-43.

Caumo A, Perseghin G, Lattuada G, Ragogna F, Brunani A, Luzi L. Comparing the original (HOMA1) and the updated (HOMA2) method: evidence that HOMA2 is more reliable than HOMA1. Diabetes. 2007;56(1):A406.

van der Aa MP, Marieke AJE , van Mil EGAG, Knibbe CAJ, van der Vorst MMJ. Metformin: an efficacy, safety and pharmacokinetic study on the short-term and long-term use in obese children and adolescents- study protocol of a randomized controlled study, van der Aa et al. Trials. 2014;15:207.

He M, Deng C, Huang XF. The Role of Hypothalamic H1 Receptor Antagonism in Antipsychotic-Induced Weight Gain. CNS Drugs. 2013;27:423-34.

Poyurovsky M, Fuchs C, Pashinian A, Levi A, Weizman R, Weizman A. Reducing antipsychotic-induced weight gain in schizophrenia: a double-blind placebo-controlled study of reboxetinebetahistine combination. Psychopharmacology. 2013;226:615-22.

Jiamei Lian, Xu-Feng H, Pai N, Chao D. Effects of olanzapine and betahistine co-treatment on serotonin transporter, 5-HT2A and dopamine D2 receptor binding density, Progress in Neuro- Psychopharmacology and Biological Psychiatry. 2013;47:62-8.

Barak N, Greenway FL, Fujioka K, Aronne LJ, Kushner RF. Effect of histaminergic manipulation on weight in obese adults: a randomized placebo controlled trial. International Journal of Obesity. 2008;32:1559-65.

Heal DJ, Gosden J, Smith SL. What is the prognosis for new centrally-actin anti-obesity drugs? Neuropharmacology. 2012;63(1):132-46.

Stanford J, Kaiser M, Ablah E, Dong F, Paull- Forney B, Early J. The effect of weight loss on fasting blood sugars and hemoglobin A1c in overweight and obese diabetics and non-diabetics. Journal of Diabetes Mellitus. 2012;2:126-30.

Chowdhuy S, Carmichael KA. How valuable is measurement of C-peptide and insulin levels in type-2 diabetes? Consultant. 2012;52(7):1.

Palmer J, Fleming G, Greenbaum C. C-peptide is the appropriate outcome measure for type 1 diabetes clinical trials to preserve B-cell function. Diabetes. 2004;59:250-64.

Levy JC, Matthews DR, Hermans MP. Correct homeostasis model assessment (HOMA) evaluation uses the computer program (Letter). Diabetes Care. 1998;21:2191-2.

Ferrannini E, Camastra S, Gastaldelli A, Maria Sironi A, Natali A, Muscelli E, et al. beta-cell function in obesity: effects of weight loss. Diabetes. 2004;53(3):S26-33.

Nagi DK, Yudkin JS. Effects of metformin on insulin resistance, risk factors for cardiovascular disease, and plasminogen activator inhibitor in NIDDM subjects. A study of two ethnic groups. Diabetes Care. 1993;16(4):621-9.

Villareal DT, Shah K, Banks MR, Sinacore DR, Klein S. Effect of weight loss and exercise therapy on bone metabolism and mass in obese older adults: a one-year randomized controlled trial. J Clin Endocrinol Metab. 2008;93(6):2181-7.

Fulop AK, Foldes A, Buzas E, Hegyi K, Miklos IH, Romics L, et al. Hyperleptinemia, visceral adiposity, and decreased glucose tolerance in mice with a targeted disruption of the histidine decarboxylase gene. Endocrinology. 2003;144:4306-14.

Barrett-O'Keefe Z, Kaplon RE, Halliwill JR. Sustained postexercise vasodilatation and histamine receptor activation following small muscle-mass exercise in humans. Exp Physiol. 2013;98(1):268-77.

Wang KY, Tanimoto A, Yamada S, Guo X, Ding Y, Watanabe T, et al. Histamine regulation in glucose and lipid metabolism via histamine receptors: model for nonalcoholic steatohepatitis in mice. Am J Pathol. 2010;177(2):713-23.

Ali AH, Yanoff LB, Stern EA, Akomeah A, Courville A, Kozlosky M, et al. Acute effects of betahistine hydrochloride on food intake and appetite in obese women: a randomized, placebo-controlled trial. Am J Clin Nutr. 2010;92(6):1290-7.

Jeck-Thole S, Wagner W. Betahistine: a retrospective synopsis of safety data.Drug Saf. 2006;29(11):1049-59.

Lezius F, Adrion C, Mansmann U, Jahn K, Michael S. High-dosage betahistine dihydrochloride between 288 and 480 mg/day in patients with severe Menière‘s disease: a case series. European Archives of Oto-Rhino-Laryngology. 2011;268:1237-40.

Downloads

Published

2016-12-24

How to Cite

Al-Anbari, H. H., Sahib, A. S., & Al-Mukhtar, A. O. (2016). Role of betahistine in glycemic control of obese subjects: a placebo- controlled clinical trial. International Journal of Basic & Clinical Pharmacology, 6(1), 167–175. https://doi.org/10.18203/2319-2003.ijbcp20164774

Issue

Section

Original Research Articles