"Hidden Corners" - about "metformin" and "vitamin B12 deficiency", these points must be known

Introduction: Metformin is widely used in clinical practice
as a first-line drug for type 2 diabetes.

Short-term application, except for rare events of lactic acidosis, with good overall safety; In the long term, metformin use is strongly
associated with vitamin B12 deficiency.

Clinical attention should be paid to
vitamin B12 deficiency or causes/exacerbates diabetes distal symmetry and autonomic neuropathy.

At the just-concluded "2022 European Association for Diabetes Research Annual Meeting", some scholars shared a study entitled "Metformin and VB12 Deficiency: A Retrospective Study on the Prevalence of VB12 Deficiency in Patients Taking Metformin", which provides more information
for understanding the "correlation between metformin use and VB12 deficiency".

Regarding the lack of metformin and VB12, EASD brings the latest data!

This is a retrospective study in which researchers observed the association
between long-term use of metformin and VB12 level deficiency in about 10,000 patients.

The study found that the average interval from taking metformin to the onset of VB12 deficiency was 7.
4 years and showed a dose correlation
.

The researchers caution that health damage
can be prevented by actively monitoring VB12 levels.

However, if not monitored, neuropathy due to VB12 deficiency may be mistaken for diabetic neuropathy
.

In addition, when patients start metformin therapy, patients are informed to monitor VB12 levels regularly and should be one
of the indicators of monitoring during routine treatment.

"Metformin" and "vitamin B12 deficiency", these points must be known

Metformin is a drug approved for the treatment of type 2 diabetes and also helps prevent the development of type 2 diabetes in patients at high risk of type 2 diabetes
.

Metformin is available in immediate-release and extended-release tablets as well as oral solutions
.

VB12 (Cobalamin) is a nutrient that helps maintain the health of the body's nerves and blood cells
.

It is found in foods of animal origin, including milk, cheese, yogurt, and eggs
.

Some foods are also additive, such as breakfast cereals
.

Common causes of VB12 deficiency include infection, malabsorption, medical conditions (Crohn's disease, pernicious anemia), gastrectomy, and inadequate dietary intake
.

1.

Decreased VB12 levels are known consequences
of long-term treatment with metformin.

The mechanism is currently considered multifactorial, including altered gut motility, bacterial overgrowth, and decreased intestinal VB12 uptake (or a combination of these factors
).

2.
What symptoms may occur in VB12 deficiency?

Patients with VB12 deficiency may be asymptomatic, may also have symptoms of megaloblastic anemia or neuropathy, or both
.

Other symptoms of low VB12 levels may include mental disorders (depression, irritability, cognitive impairment), glossitis (swelling and inflammation of the tongue), mouth ulcers, and visual and motor impairments
.

For patients with anemia or neuropathy caused by VB12 deficiency, early diagnosis and treatment is particularly important
to avoid permanent symptoms.

3.
How long is metformin medication, prone to VB12 deficiency?

Previous studies have suggested that metformin causes VB12 deficiency in a dose- and treatment duration-dependent manner, but vitamin B12 deficiency
usually occurs 4 to 5 years after metformin use.

That's because the average storage of vitamin B12 in the liver is 2500 PPIC, and in most cases, at least a few years of metformin use will deplete these reserves
.

4.
Is the dose of metformin associated with VB12 deficiency?

Studies have shown that over a period of at least six months of administration, compared with a daily dose of metformin of 1000 mg or less:

➤ Patients taking 1000 mg to 1500 mg of metformin daily increased the risk of VB12 deficiency by 72% (p=0.
8);
➤ Patients taking 1500 mg to 2000 mg of metformin daily increased risk of VB12 deficiency by 334% (p=0.
001);
➤ Patients taking more than 2,000 mg of metformin daily had an increased risk of VB12 deficiency by 867% (p=0.
01).

Prevention and management: metformin and vitamin B12 deficiency

1.
Plan ahead: Pay attention to risk factors

Risk factors for VB12 deficiency range and include:

➤ Baseline VB12 level is at the lower limit of the normal range;

➤ Disorders associated with decreased absorption of VB12 (eg, in the elderly and in patients with gastrointestinal disorders, such as total gastrectomy or partial gastrectomy, Crohn's disease and other inflammatory or autoimmune diseases);

➤ Decreased sources of VB12 in the diet (such as diets for vegans and some vegetarians);

➤ Companion medications known to impair VB12 absorption (including proton pump inhibitors or colchicine);

➤ VB12 deficiency genetic predisposition such as endofactor receptor deficiency (Imerslund-Grsbeck syndrome) and transcobalamin II deficiency
.

2.
Medication knowledge: doctor's article

➤Metformin usually reduces VB12 levels in patients, which can lead to VB12 deficiency;

➤Higher metformin doses, longer treatment duration, and risk factors for VB12 deficiency in patients are accompanied by an increased risk of low VB12 levels;

➤ Detect VB12 serum levels when VB12 deficiency is suspected (eg, in patients with megaloblastic anemia or new-onset neuropathy) and follow current clinical guidelines for the detection and management of VB12 deficiency;

➤ Consider regular VB12 monitoring for patients with risk factors for VB12 deficiency (see list of risk factors below);

➤ Corrective treatment of VB12 deficiency in accordance with current clinical guidelines; If metformin is tolerated and there are no contraindications, metformin therapy
is continued.

3.
Medication knowledge: patient article

➤ If you are taking metformin, seek medical advice when you are experiencing new symptoms of extreme tiredness, tongue aches and redness, numbness, pallor skin, or worsening of these symptoms (which may be a sign of low VB12 levels);

➤ Blood tests may be required to find out the cause of the symptoms; These symptoms can also be caused by diabetes or other unrelated health problems;

➤ Can continue to take metformin while correcting VB12 levels;

➤ Do not stop treatment
without discussing it with your doctor.

About the author

Han Jie

Department of Endocrinology, First Hospital of Lanzhou University, deputy chief physician, doctor of medicine, secretary of the endocrine branch of Gansu Provincial Medical Association, has been in Copenhagen Hvidovre Hospital, Denmark, Tianjin Medical University, UCLA David Geffen School of Medicine for further study and exchange studies
.

He participated in the completion of three projects of the National Natural Science Foundation of China, participated in 2 follow-up visits to the Special Fund of the Chinese Medical Association (REACTION Research), participated in 3 scientific and technological projects in Gansu Province, participated in the publication of 9 papers, presided over 3 scientific research projects, participated in the compilation of 2 monographs, won the first prize of the Lanzhou University Teaching Achievement Award, and won 2 second prizes
of the Gansu Medical Science and Technology Award.

Served as a consultant for UPTODATE Chinese in the United States to translate 5 professional documents
.