Dosage Reduction and Acute Glycemic Complications in People With Type 2 Diabetes Who Fast During Ramadan

Effect of Dosage Reduction of Glucose-Lowering Multidrug Regimens on the Incidence of Acute Glycemic Complications in People With Type 2 Diabetes Who Fast During Ramadan: An Open-Label, Parallel-Group, Randomized, Controlled Trial

Every lunar year, during the month of Ramadan, Muslims abstain from food and drink between dawn and nightfall. People with type 2 diabetes who fast during Ramadan are at an increased risk of acute glycemic complications. Our aim is to investigate the effect of dosage reduction of four glucose-lowering multidrug regimens on the incidence of acute glycemic complications in people with type 2 diabetes who fast during Ramadan.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2
• Intervention / Treatment: Drug: Metformin and Glimepiride (Low Dosage); Drug: Metformin and Vildagliptin (Low Dosage); Drug: Metformin and Insulin Glargine U100 (Low Dosage); Drug: Metformin, Insulin Glargine U100, and Human Regular Insulin (Low Dosage); Drug: Metformin and Glimepiride (Regular Dosage); Drug: Metformin and Vildagliptin (Regular Dosage); Drug: Metformin and Insulin Glargine U100 (Regular Dosage); Drug: Metformin, Insulin Glargine U100, and Human Regular Insulin (Regular Dosage)

• Study Type: Interventional
• Enrollment (Actual): 687
• Phase: Phase 4

Contacts and Locations

Study Locations

• Jordan
  • Amman Governorate
    • Amman, Amman Governorate, Jordan, 11942
      • Jordan University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Prospective participant is a returning patient with type 2 diabetes;
• Prospective participant expressed an intention to fast during Ramadan;
• Prospective participant has been compliant with one of four glucose-lowering multidrug regimens for at least the past three months.

Exclusion Criteria:

• Prospective participant is a pregnant, postpartum, breastfeeding, or eumenorrheic woman;
• Prospective participant has experienced diabetic ketoacidosis or hyperosmolar hyperglycemic state within three months;
• Prospective participant has received niacin or corticosteroids within one month; and,
• Prospective participant has any history of recurrent hypoglycemia, hypoglycemia unawareness, chronic renal insufficiency (stages IV or V), liver cirrhosis, uncontrolled epilepsy, depressive disorder, bipolar disorder, psychotic disorder, or cognitive dysfunction.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Low-dosage therapy	Drug: Metformin and Glimepiride (Low Dosage); Metformin (PO; 850 mg; BID [with Ifṭār and with Suḥūr]); Glimepiride (PO; 1.5 or 3 mg [75% of the pre-Ramadan dose]; OD [with Ifṭār]); Drug: Metformin and Vildagliptin (Low Dosage); Metformin (PO; 850 mg; BID [with Ifṭār and with Suḥūr]); Vildagliptin (PO; 50 mg; OD [with Ifṭār]); Drug: Metformin and Insulin Glargine U100 (Low Dosage); Metformin (PO; 850 mg; BID [with Ifṭār and with Suḥūr]); Insulin Glargine U100 (SC; 9-33 units [75% of the pre-Ramadan dose]; OD [at 10 P.M.]); Drug: Metformin, Insulin Glargine U100, and Human Regular Insulin (Low Dosage); Metformin (PO; 850 mg; BID [with Ifṭār and with Suḥūr]); Insulin Glargine U100 (SC; 6-39 units (75% of the pre-Ramadan dose); OD [at 10 P.M.]); Human Regular Insulin (SC; 15-33 units before Ifṭār and 6-18 units before Suḥūr [75% of the pre-Ramadan doses])
Active Comparator: Regular-dosage therapy	Drug: Metformin and Glimepiride (Regular Dosage); Metformin (PO; 850 mg; BID [with Ifṭār and with Suḥūr]); Glimepiride (PO; 2 or 4 mg [100% of the pre-Ramadan dose]; OD [with Ifṭār]); Drug: Metformin and Vildagliptin (Regular Dosage); Metformin (PO; 850 mg; BID [with Ifṭār and with Suḥūr]); Vildagliptin (PO; 50 mg; BID [with Ifṭār and with Suḥūr]]); Drug: Metformin and Insulin Glargine U100 (Regular Dosage); Metformin (PO; 850 mg; BID [with Ifṭār and with Suḥūr]); Insulin Glargine U100 (SC; 11-44 units [100% of the pre-Ramadan dose]; OD [at 10 P.M.]); Drug: Metformin, Insulin Glargine U100, and Human Regular Insulin (Regular Dosage); Metformin (PO; 850 mg; BID [with Ifṭār and with Suḥūr]); Insulin Glargine U100 (SC; 8-52 units (100% of the pre-Ramadan dose); OD [at 10 P.M.]); Human Regular Insulin (SC; 12-40 units before Ifṭār and 7-28 units before Suḥūr [100% of the pre-Ramadan doses])

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hypoglycemia	Incidence of hypoglycemia	29 days of Ramadan
Hyperglycemia	Incidence of hyperglycemia	29 days of Ramadan

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diabetic ketoacidosis	Incidence of diabetic ketoacidosis	29 days of Ramadan
Hyperosmolar hyperglycemic state	Incidence of hyperosmolar hyperglycemic state	29 days of Ramadan

Collaborators and Investigators

• Sponsor: University of Jordan
• Investigators: Principal Investigator: Ayman A. Zayed, MD, The University of Jordan School of Medicine

Publications and helpful links

General Publications

• Zaghlol LY, Beirat AF, Amarin JZ, Hassoun Al Najar AM, Hasan YY, Qtaishat A, Tierney ME, Zaghlol RY, Zayed AA. 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. Front Endocrinol (Lausanne). 2021 Jul 7;12:613826. doi: 10.3389/fendo.2021.613826. eCollection 2021.

Study record dates

Study Major Dates

• Study Start (Actual): February 14, 2017
• Primary Completion (Actual): July 24, 2017
• Study Completion (Actual): July 24, 2017

Study Registration Dates

• First Submitted: January 17, 2020
• First Submitted That Met QC Criteria: January 17, 2020
• First Posted (Actual): January 23, 2020

Study Record Updates

• Last Update Posted (Actual): February 11, 2020
• Last Update Submitted That Met QC Criteria: February 9, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Keywords: Hypoglycemia; Metformin; Hyperglycemia; Diabetes Mellitus, Type 2; Fasting; Hypoglycemic Agents; Glimepiride; Insulin Glargine; Vildagliptin; Diabetic Ketoacidosis; Hyperglycemic Hyperosmolar Nonketotic Coma; Insulin, Regular, Human
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Enzyme Inhibitors; Immunosuppressive Agents; Immunologic Factors; Protease Inhibitors; Dipeptidyl-Peptidase IV Inhibitors; Insulin; Insulin, Globin Zinc; Metformin; Insulin Glargine; Glimepiride; Vildagliptin
• Other Study ID Numbers: 671201612222

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No