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Metformin Usage Index and Vitamin B12 Status in Egyptian Type 2 Diabetic Patients

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ClinicalTrials.gov Identifier: NCT04882332
Recruitment Status : Recruiting
First Posted : May 11, 2021
Last Update Posted : March 24, 2022
Information provided by (Responsible Party):
Mona Youssry Helmy, Cairo University

Brief Summary:

Current data estimated that 451 million people, (age 18-99 years) suffered from diabetes world wide in 2017, and are expected to rise to 693 million by 2045. Among them, type 2 diabetes mellitus (T2DM) accounts for around 90% of all cases with diabetes.

T2DM is associated with several deterimental microvascular and macrovascular complications (Annani-Akollor ME et al ., 2019) . As such, effective management of the disease is crucial.

The American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) recommend metformin as the first therapeutic choice for T2DM management with concurrent lifestyle modifications. Reports indicated that metformin improves peripheral insulin sensitivity and reduces the risk of cardiovascular mortality in T2DM in addition to its beneficial effects on weight loss and vascular protection.

Nonetheless, as with most medications, metformin has some side effects. Though most of these side effects are mild, reports indicated that metformin use is associated with diminution of vitamin B12 level . Also, advanced age of patients with T2DM, nutritional deficiency, and malabsorption are other contributing factors for its deficiency .

The proposed mechanisms for deficiency include, impairment of calcium dependent absorption from the gut, alteration in small bowel motility resulting in bacterial overgrowth, and a reduction in intrinsic factor levels .

Metformin-induced vitamin B12 deficiency has also been associated with neuropathy. The neuropathy associated with vitamin B12 deficiency ranges from paresthesia and attenuated peripheral sensation in response to changes in mental status and proprioception which overlap with diabetic neuropathy.

The progression of vitamin B12 deficiency-induced neurologic damage can, however, be abated through early detection and vitamin B12 therapy. Nonetheless, if peripheral neuropathy due to deficiency of vitamin B12 is misconstrued as diabetic peripheral neuropathy , permanent neurological damage may occur.

Several studies have investigated the individual effects of the dose and duration of metformin therapy on vitamin B12 levels .The reported results are inconsistent, with some studies reporting an association with the dose but not the duration and other studies reporting an association only for the duration. however, A few studies did not find an association with either the dose or the duration..

This could be attributed to the fact that, in any given patient with T2DM, vitamin B12 levels could be influenced predominantly by either the dose or the duration of metformin therapy. Hence, it is important to involve both the dose and duration of metformin therapy into the assessment of vitamin B12 deficiency.

Micronutrient deficiencies constitute a global health issue, particularly among countries in the Middle East .The World Health Organization (WHO) has divided this region into overlapping country clusters with regard to nutrition stages and dominant nutrition problems, including major risk factors and underlying causes, program interventions, and gaps in response to these problems.

Countries in early nutrition transition (e.g., Egypt, Jordan, Lebanon, Morocco, and Palestine) are typically characterized by a moderate prevalence of overweight and obesity, moderate levels of undernutrition in specific population groups, and widespread micronutrient deficiencies/inadequacies.

Metformin Usage Index is the product of the dose of metformin (mg) used and its duration divided by 1000. An index which incorporates both of these factors would not only be useful to understand the cumulative impact on vitamin B12 levels but also provide an objective threshold for initiating vitamin B12 supplementation .

So , the aim of this study is to assess the relationship between the dose and duration of metformin therapy with vitamin B12 levels using the "Metformin Usage Index" (MUI) in Egyptian type 2 diabetic patients where the incidence of nutritional deficiencies are not uncommom in order to formulate their appropriate management strategies .

The aim of our study is to evaluate the combined effect of both dose and duration of metformin therapy on vitamin B12 levels in Egyptian patients with type 2 diabetes mellitus (T2D).

Condition or disease Intervention/treatment
Diabetes Mellitus Other: sampling for diabetes control parameters Other: Sampling for vitamin B12 level

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Study Type : Observational
Estimated Enrollment : 108 participants
Observational Model: Case-Control
Time Perspective: Prospective
Official Title: Metformin Usage Index and Vitamin B12 Status in Egyptian Type 2 Diabetic Patients : A Case Control Study .
Actual Study Start Date : May 5, 2021
Estimated Primary Completion Date : September 2022
Estimated Study Completion Date : October 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: B Vitamins

Group/Cohort Intervention/treatment
metformin usage index and vitamin B12 level
Samples for correlation between metformin usage index and vitamin B1 level will be withdrawn from 108 type 2 diabetes patients
Other: sampling for diabetes control parameters
Intravenous blood withdrawal for a sample of fasting blood glucose (FBG), 2 hr postprandial blood glucose (2 hr -PPG), fasting lipids {total cholesterol (TC), triglycerides (TAG), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C)}, glycosylated hemoglobin (Hb A1c) ,fasting insulin level and Vitamin B 12 levels

Other: Sampling for vitamin B12 level
Intravenous blood sampling for a sample of vitamin B12 level

Primary Outcome Measures :
  1. Correlation between Metformin Usage Index and Vitamin B12 status among Egyptian patients with type 2 diabetes [ Time Frame: 6 months ]
    The relationship between MUI and vitamin B12 levels will be assessed among the studied groups

Information from the National Library of Medicine

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Ages Eligible for Study:   20 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
108 patients aged 20 to 65 years old with controlled and uncontrolled type 2 DM

Inclusion Criteria:

  • Men and women aged 20 to 65 years old with controlled and uncontrolled type 2 DM

Exclusion Criteria:

  • T2DM patients who are pregnant/lactating women,
  • newly diagnosed with T2DM (< 3 months),
  • who receive vitamin B12 supplementation or proton-pump inhibitors over the last 6 months,
  • alcoholics ,
  • known cases of malabsorption (gastrointestinal surgery, inflammatory bowel diseases and gluten allergy),
  • chronic kidney disease,
  • pernicious anemia

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04882332

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Contact: Nehal H Elsaid 01004389020 ext 02 nihalhamdyelsaid@yahoo.com
Contact: Sherif Abdullah 01002013497 ext 02 Dr.Sherif213@yahoo.com

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Cairo University Recruiting
Cairo, Manial, Egypt, 11521
Contact: Mona Youssry, M.D.    01004389020 ext 01004389020    mona55508@yahoo.com   
Sponsors and Collaborators
Cairo University
Ahmed MA, Muntingh G, Rheeder P (2016) Vitamin B12 deficiency in metformin-treated type-2 diabetes patients, prevalence and association with peripheral neuropathy. BMC Pharmacol Toxicol 17(1):44. https ://doi.org/10.1186/s4036 0-016-0088-3. Alvarez M, Sierra OR, Saavedra G, Moreno S (2019) Vitamin B12 deficiency and diabetic neuropathy in patients taking metformin: a cross-sectional study. Endocr Connect 8(10):1324- 1329. https ://doi.org/10.1530/EC-19-0382. Annani-Akollor ME, Addai-Mensah O, Fondjo LA, et al.(2019) Predominant complications of type 2 diabetes in kumasi: a 4-year retrospective cross-sectional study at a teaching hospital in Ghana. Medicina (B Aires). 2019;55(5): 125.

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Responsible Party: Mona Youssry Helmy, Lecturer of internal medicine, Cairo University
ClinicalTrials.gov Identifier: NCT04882332    
Other Study ID Numbers: N-25-2021
First Posted: May 11, 2021    Key Record Dates
Last Update Posted: March 24, 2022
Last Verified: March 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: not to share

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Mona Youssry Helmy, Cairo University:
metformin usage index
vitamin b 12 status
diabetes control
Additional relevant MeSH terms:
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Vitamin B 12
Physiological Effects of Drugs
Vitamin B Complex