Metformin

Background
Vitamin B12 deficiency is common in the elderly population and can cause severe complications. The use of certain medication has in previous studies been associated with vitamin B12 deficiency in the general population. To identify elderly patients at risk for vitamin B12 deficiency due to medication use, we evaluated the association between medication use and vitamin B12 deficiency in the elderly population.

Methods
Hospitalized geriatric patients 65 years of age or over with a serum vitamin B12 measurement within one week of the admittance date were included. Patients were classified as either B12 normal (258–635 pmol/L) or B12 deficient (< 148 pmol/L). Upon hospital admission patients’ medication use was verified. The association between vitamin B12 deficiency and the use of antacid, antiepileptic, antidiabetic, lipid lowering and other medication was evaluated by univariate and multivariate analyses.

Results
Of the 7132 patients included in the study, 532 (7.5%) had vitamin B12 deficiency and 3433 (48.1%) patients had normal vitamin B12 concentrations. Metformin use was significantly and independently (adjusted OR 2.5; 95% CI 1.7–3.6) associated with a dose-dependent higher risk of vitamin B12 deficiency. The use of other medication evaluated in this study was not associated with vitamin B12 deficiency.

Conclusions
Metformin use is significantly associated with vitamin B12 deficiency in the elderly, and this risk rises with higher metformin doses. Monitoring and timely start of vitamin B12 supplementation along with the lowest possible metformin dose are essential to prevent complications.

Author/s:

Monique P H Tillemans, Thijs J Giezen, Toine C G Egberts, Kees J Kalisvaart

Diagnosis and Treatment of Type 2 Diabetes in Adults A Review

Hope Smashey — Tue, 01 Jul 2025 19:34:58 +0000

Date Added:

July 1, 2025

Journal/Publication:

JAMA

Publication Date:

June 23, 2025

URL:

Diagnosis and Treatment of Type 2 Diabetes in Adults: A Review

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.1001/jama.2025.5956

Keywords

diabetes

type 2 diabetes

treatment

PMID (1):

40549398

MeSH

diabetes mellitus

Type 2

cardiovascular diseases

dipeptidyl-peptidase IV inhibitors

Insulin Resistance

Insulin Secretion

Glucose Tolerance Test

overweight

risk factors

An evidence-based review of the treatment of patients with Type 2 diabetes mellitus. James W. Mold, MD, MPH

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Importance: Type 2 diabetes involves progressive loss of insulin secretion from pancreatic β cells in the setting of insulin resistance and manifests clinically as hyperglycemia. Type 2 diabetes accounts for 90% to 95% of all cases of diabetes globally, with estimates ranging from 589 million to 828 million people worldwide. In the US, type 2 diabetes affects approximately 1 in 6 adults.

Observations: Risk factors for type 2 diabetes include older age, family history, overweight or obesity, physical inactivity, gestational diabetes, Hispanic ethnicity, and American Indian or Alaska Native, Asian, or Black race. Diabetes is diagnosed if fasting plasma glucose is greater than or equal to 126 mg/dL, hemoglobin A1C is greater than or equal to 6.5%, or 2-hour glucose during 75-g oral glucose tolerance testing is greater than or equal to 200 mg/dL. Approximately one-third of adults with type 2 diabetes have cardiovascular disease and 10.1% have severe vision difficulty or blindness. The prevalence of type 2 diabetes is 39.2% among patients with kidney failure. Although weight management is an important component of treatment for type 2 diabetes, no specific diet has been proven to be most effective for improving health outcomes. Physical activity can reduce hemoglobin A1C by 0.4% to 1.0% and improve cardiovascular risk factors (ie, hypertension and dyslipidemia). Randomized clinical trials have reported absolute reductions in microvascular disease (3.5%), such as retinopathy and nephropathy, myocardial infarction (3.3%-6.2%), and mortality (2.7%-4.9%), with intensive glucose-lowering strategies (hemoglobin A1C <7%) vs conventional treatment 2 decades after trial completion. First-line medications for type 2 diabetes include metformin and, in patients with cardiovascular or kidney comorbidities or at high cardiovascular risk, glucagon-like peptide-1 receptor agonists (GLP-1RAs) or sodium-glucose cotransporter 2 inhibitors (SGLT2is). Common add-on medications include dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1RAs, dipeptidyl peptidase-4 inhibitors, sulfonylureas, and thiazolidinediones. Approximately one-third of patients with type 2 diabetes require treatment with insulin during their lifetime. Several randomized clinical trials have demonstrated benefits of specific SGLT2i and GLP-1RA medications compared with placebo for atherosclerotic cardiovascular disease (12%-26% risk reduction), heart failure (18%-25% risk reduction), and kidney disease (24%-39% risk reduction) over 2 to 5 years. Most trial participants with type 2 diabetes were taking metformin. High-potency GLP-1RA and dual GIP/GLP-1RA medications result in weight loss of greater than 5% in most individuals with type 2 diabetes, and weight loss may exceed 10%.

Conclusions: Type 2 diabetes affects up to 14% of the global population and is associated with preventable long-term complications, such as cardiovascular disease, kidney failure, vision loss, and increased mortality. In addition to lifestyle modifications including diet, exercise, and weight management, metformin is generally first-line therapy for attainment of hemoglobin A1C targets. For individuals with type 2 diabetes and cardiovascular or kidney disease or at high cardiovascular risk, guidelines recommend early treatment with SGLT2i and/or GLP-1RA medications.

Author/s:

Rita R Kalyani, Joshua J Neumiller, Nisa M Maruthur, Deborah J Wexler

The relationship between exacerbated diabetic peripheral neuropathy and metformin treatment in type 2 diabetes mellitus

Devin Evans — Wed, 03 Mar 2021 06:00:00 +0000

Date Added:

March 3, 2021

Journal/Publication:

Scientific Reports

Publication Date:

January 21, 2021

Issue:

Volume:

URL:

The relationship between exacerbated diabetic peripheral neuropathy and metformin treatment in type 2 diabetes mellitus

Type:

Clinical Research Results

Format:

Article

DOI (1):

10.1038/s41598-021-81631-8

Keywords

PMID (1):

33479439

MeSH

Metformin

diabetic neuropathies

This study suggests that prolonged treatment with metformin is associated with reduced Vitamin B12 levels and an increased incidence of distal peripheral neuropathy. James W. Mold, MD, MPH

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Metformin-treated diabetics (MTD) showed a decrease in cobalamin, a rise in homocysteine, and methylmalonic acid, leading to accentuated diabetic peripheral neuropathy (DPN). This study aimed to determine whether or not metformin is a risk factor for DPN. We compared MTD to non-metformin-treated diabetics (NMTD) clinically using the Toronto Clinical Scoring System (TCSS), laboratory (methylmalonic acid, cobalamin, and homocysteine), and electrophysiological studies. Median homocysteine and methylmalonic acid levels in MTD vs. NMTD were 15.3 vs. 9.6 µmol/l; P < 0.001 and 0.25 vs. 0.13 µmol/l; P = 0.02, respectively with high statistical significance in MTD. There was a significantly lower plasma level of cobalamin in MTD than NMTD. Spearman's correlation showed a significant negative correlation between cobalamin and increased dose of metformin and a significant positive correlation between TCSS and increased dose of metformin. Logistic regression analysis showed that MTD had significantly longer metformin use duration, higher metformin dose > 2 g, higher TCSS, lower plasma cobalamin, and significant higher homocysteine. Diabetics treated with metformin for prolonged duration and higher doses were associated with lower cobalamin and more severe DPN.

Author/s:

Hashem, Manal Mohammed, Esmael, Ahmed, Nassar, Abdelfattah Kasem, El-Sherif, Mohammed

Using Insulin to Treat Poorly Controlled Type 2 Diabetes in 2020

John Bayhi — Tue, 26 May 2020 20:43:16 +0000

Date Added:

May 26, 2020

Journal/Publication:

JAMA

Publisher:

American Medical Association

Publication Date:

May 22, 2020

Volume:

Online ahead of print

URL:

Using Insulin to Treat Poorly Controlled Type 2 Diabetes in 2020

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.1001/jama.2020.1303

Keywords

PMID (1):

32442246

MeSH

Sodium-Glucose Transporter 2 Inhibitors

hypoglycemic agents

insulin

glycated hemoglobin a

dipeptidyl-peptidase IV inhibitors

Metformin

diabetes mellitus, type 2

Glucagon-Like Peptide-1 Receptor

Thiazolidinediones

A potentially useful decision algorithm for management of patients with Type 2 diabetes, which includes early consideration of use of basal insulin in patients with A1c > 9%. James W. Mold, MD, MPH

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No abstract available

Author/s:

Hirsch, IB, Gaudiani, LM