Effect of Dosage Reduction of Hypoglycemic Multidrug Regimens on the Incidences of Acute Glycemic Complications in People With Type 2 Diabetes Who Fast During Ramaḍān: A Randomized Controlled Trial

Louay Y Zaghlol, Amir F Beirat, Justin Z Amarin, Amro M Hassoun Al Najar, Yazan Y Hasan, Abdallah Qtaishat, Michael E Tierney, Raja Y Zaghlol, Ayman A Zayed, Louay Y Zaghlol, Amir F Beirat, Justin Z Amarin, Amro M Hassoun Al Najar, Yazan Y Hasan, Abdallah Qtaishat, Michael E Tierney, Raja Y Zaghlol, Ayman A Zayed

Abstract

Objective: We aimed to investigate the effect of dosage reduction of four hypoglycemic multidrug regimens on the incidences of acute glycemic complications in people with type 2 diabetes who fast during Ramaḍān.

Methods: We conducted an open-label, parallel-group, randomized controlled trial at a tertiary care center in Amman, Jordan. We recruited adults with type 2 diabetes who expressed an intention to fast during Ramaḍān and were adherent to one of four regimens-namely: metformin and glimepiride; metformin and vildagliptin; metformin and insulin glargine U100; or, metformin, insulin glargine U100, and human regular insulin. We randomly assigned participants in a 2:1 ratio to low- or regular-dosage therapy. The primary outcomes were the incidences of hypoglycemia and hyperglycemia during the 29 days of Ramaḍān 2017, and the secondary outcomes were the incidences of diabetic ketoacidosis and hyperosmolar hyperglycemic state during the same period.

Results: We randomly assigned 687 participants to low-dosage therapy (n = 458) or regular-dosage therapy (n = 229) and included 678 (452 and 226, respectively) in the final analysis. The incidence of hypoglycemia was lower in the low-dosage group compared with the regular-dosage group (19 [4.2%] vs. 52 [23.0%], respectively; OR, 0.15 [95% CI, 0.08-0.26]; P < 0.001). The incidence of hyperglycemia did not differ between the low- and regular-dosage groups (319 [70.6%] vs. 154 [68.1%], respectively; OR, 1.12 [95% CI, 0.79-1.58]; P = 0.5). No participants experienced diabetic ketoacidosis or hyperosmolar hyperglycemic state. Each 1% decrease in the baseline HbA1c concentration was associated with a 19.9-fold (95% CI, 9.6-41.5; P < 0.001) increase in the odds of hypoglycemia, and each 1% increase in the baseline HbA1c concentration was associated with a 15.7-fold (95% CI, 10.0-24.6; P < 0.001) increase in the odds of hyperglycemia.

Conclusion: Dosage reduction decreases the incidence of hypoglycemia without a concomitant increase in the incidences of hyperglycemia, diabetic ketoacidosis, and hyperosmolar hyperglycemic state in people with type 2 diabetes who fast during Ramaḍān.

Clinical trial registration: www.ClinicalTrials.gov, identifier NCT04237493.

Keywords: fasting; hyperglycemia; hypoglycemia; hypoglycemic agents; type 2 diabetes mellitus.

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2021 Zaghlol, Beirat, Amarin, Hassoun Al Najar, Hasan, Qtaishat, Tierney, Zaghlol and Zayed.

Figures

Figure 1
Figure 1
CONSORT flow diagram. (N = 678 participants).

References

    1. Al-Arouj M, Assaad-Khalil S, Buse J, Fahdil I, Fahmy M, Hafez S, et al. . Recommendations for Management of Diabetes During Ramadan: Update 2010. Diabetes Care (2010) 33:1895–902. 10.2337/dc10-0896
    1. Salti I, Bénard E, Detournay B, Bianchi-Biscay M, Le Brigand C, Voinet C, et al. . A Population-Based Study of Diabetes and Its Characteristics During the Fasting Month of Ramadan in 13 Countries: Results of the Epidemiology of Diabetes and Ramadan 1422/2001 (EPIDIAR) Study. Diabetes Care (2004) 27:2306–11. 10.2337/diacare.27.10.2306
    1. Hassan A, Meo SA, Usmani AM, Shaikh TJ. Diabetes During Ramadan – PRE-Approach Model: Presentation, Risk Stratification, Education. Eur Rev Med Pharmacol Sci (2014) 18:1798–805.
    1. Bajaj HS, Abouhassan T, Ahsan MR, Arnaout A, Hassanein M, Houlden RL, et al. . Diabetes Canada Position Statement for People With Types 1 and 2 Diabetes Who Fast During Ramadan. Can J Diabetes (2019) 43:3–12. 10.1016/j.jcjd.2018.04.007
    1. Hassanein M, Al-Arouj M, Hamdy O, Bebakar WMW, Jabbar A, Al-Madani A, et al. . Diabetes and Ramadan: Practical Guidelines. Diabetes Res Clin Pract (2017) 126:303–16. 10.1016/j.diabres.2017.03.003
    1. Belkhadir J, el Ghomari H, Klöcker N, Mikou A, Nasciri M, Sabri M. Muslims With Non-Insulin Dependent Diabetes Fasting During Ramadan: Treatment With Glibenclamide. BMJ (1993) 307:292–5. 10.1136/bmj.307.6899.292
    1. Shehadeh N, Maor Y, Ramadan Study Group . Effect of a New Insulin Treatment Regimen on Glycaemic Control and Quality of Life of Muslim Patients With Type 2 Diabetes Mellitus During Ramadan Fast – An Open Label, Controlled, Multicentre, Cluster Randomised Study. Int J Clin Pract (2015) 69:1281–8. 10.1111/ijcp.12695
    1. Hassanein M, Echtay AS, Malek R, Omar M, Shaikh SS, Ekelund M, et al. . Original Paper: Efficacy and Safety Analysis of Insulin Degludec/Insulin Aspart Compared With Biphasic Insulin Aspart 30: A Phase 3, Multicentre, International, Open-Label, Randomised, Treat-to-Target Trial in Patients With Type 2 Diabetes Fasting During Ramadan. Diabetes Res Clin Pract (2018) 135:218–26. 10.1016/j.diabres.2017.11.027
    1. Beano AM, Zmaili MA, Gheith ZH, Naser AM, Momani MS, Yousef AMF, et al. . Predetermined Anti-Diabetic Drug Regimen Adjustments During Ramadan Fasting: An Observational Study of Safety. Endocrinol Metab (Seoul) (2017) 32:265–73. 10.3803/EnM.2017.32.2.265
    1. World Health Organization . Obesity: Preventing and Managing the Global Epidemic. Geneva, Switzerland: World Health Organization; (2000).
    1. Shorr RI, Ray WA, Daugherty JR, Griffin MR. Incidence and Risk Factors for Serious Hypoglycemia in Older Persons Using Insulin or Sulfonylureas. Arch Intern Med (1997) 157:1681–6. 10.1001/archinte.157.15.1681
    1. International Hypoglycaemia Study Group . Glucose Concentrations of Less Than 3.0 mmol/L (54 mg/dL) Should Be Reported in Clinical Trials: A Joint Position Statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care (2017) 40(1):155–7. 10.2337/dc16-2215
    1. Kitabchi AE, Umpierrez GE, Miles JM, Fisher JN. Hyperglycemic Crises in Adult Patients With Diabetes. Diabetes Care (2009) 32(7):1335–43. 10.2337/dc09-9032
    1. Hassanein M, Al Awadi FF, El Hadidy KES, Ali SS, Echtay A, Djaballah K, et al. . The Characteristics and Pattern of Care for the Type 2 Diabetes Mellitus Population in the MENA Region During Ramadan: An International Prospective Study (DAR-MENA T2DM). Diabetes Res Clin Pract (2019) 151:275–84. 10.1016/j.diabres.2019.02.020
    1. Jakobsen JC, Gluud C, Wetterslev J, Winkel P. When and How Should Multiple Imputation Be Used for Handling Missing Data in Randomised Clinical Trials – a Practical Guide With Flowcharts. BMC Med Res Methodol (2017) 17(1):162. 10.1186/s12874-017-0442-1
    1. Jabbar A, Hassanein M, Beshyah SA, Boye KS, Yu M, Babineaux SM. CREED Study: Hypoglycaemia During Ramadan in Individuals With Type 2 Diabetes Mellitus From Three Continents. Diabetes Res Clin Pract (2017) 132:19–26. 10.1016/j.diabres.2017.07.014
    1. Mishriky BM, Cummings DM, Tanenberg RJ. The Efficacy and Safety of DPP4 Inhibitors Compared to Sulfonylureas as Add-on Therapy to Metformin in Patients With Type 2 Diabetes: A Systematic Review and Meta-Analysis. Diabetes Res Clin Pract (2015) 109:378–88. 10.1016/j.diabres.2015.05.025
    1. Bosi E, Camisasca RP, Collober C, Rochotte E, Garber AJ. Effects of Vildagliptin on Glucose Control Over 24 Weeks in Patients With Type 2 Diabetes Inadequately Controlled With Metformin. Diabetes Care (2007) 30:890–5. 10.2337/dc06-1732
    1. Mest HJ, Mentlein R. Dipeptidyl Peptidase Inhibitors as New Drugs for the Treatment of Type 2 Diabetes. Diabetologia (2005) 48:616–20. 10.1007/s00125-005-1707-5
    1. Halimi S, Levy M, Huet D, Quéré S, Dejager S. Experience With Vildagliptin in Type 2 Diabetic Patients Fasting During Ramadan in France: Insights From the VERDI Study. Diabetes Ther (2013) 4:385–98. 10.1007/s13300-013-0038-7
    1. Israelian Z, Szoke E, Woerle J, Bokhari S, Schorr M, Schwenke DC, et al. . Multiple Defects in Counterregulation of Hypoglycemia in Modestly Advanced Type 2 Diabetes Mellitus. Metabolism (2006) 55:593–8. 10.1016/j.metabol.2005.11.013
    1. Segel SA, Paramore DS, Cryer PE. Hypoglycemia-Associated Autonomic Failure in Advanced Type 2 Diabetes. Diabetes (2002) 51:724–33. 10.2337/diabetes.51.3.724
    1. Ahmad J, Pathan MF, Jaleel MA, Fathima FN, Raza SA, Khan AK, et al. . Diabetic Emergencies Including Hypoglycemia During Ramadan. Indian J Endocrinol Metab (2012) 16:512–5. 10.4103/2230-8210.97996
    1. Beshyah SA, Chowdhury TA, Ghouri N, Lakhdar AA. Risk of Diabetic Ketoacidosis During Ramadan Fasting: A Critical Reappraisal. Diabetes Res Clin Pract (2019) 151:290–8. 10.1016/j.diabres.2019.02.027
    1. Loke SC, Rahim KF, Kanesvaran R, Wong TW. A Prospective Cohort Study on the Effect of Various Risk Factors on Hypoglycaemia in Diabetics Who Fast During Ramadan. Med J Malaysia (2010) 65:3–6.
    1. Duckworth WC, Abraira C, Moritz TE, Davis SN, Emanuele N, Goldman S, et al. . The Duration of Diabetes Affects the Response to Intensive Glucose Control in Type 2 Subjects: The VA Diabetes Trial. J Diabetes Complications (2011) 25:355–61. 10.1016/j.jdiacomp.2011.10.003

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