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

Metformin for Knee Osteoarthritis in Patients With Overweight or Obesity: A Randomized Clinical Trial

Alex Haga — Thu, 29 May 2025 13:14:00 +0000

Date Added:

May 29, 2025

Journal/Publication:

JAMA

Publication Date:

April 24, 2025

Issue:

Volume:

333

Pages:

1804-1812

URL:

Metformin for Knee Osteoarthritis in Patients With Overweight or Obesity: A Randomized Clinical Trial

Type:

Clinical Research Results

Format:

Article

DOI (1):

10.1001/jama.2025.3471

Keywords

PMID (1):

40274279

MeSH

Hypoglycemic Agents* / therapeutic use

Metformin* / therapeutic use

Obesity* / complications

osteoarthritis

Knee* / complications

Metformin 2000mg per day appears to reduce the pain of osteoarthritis of the knees in people who are overweight or obese. James W. Mold, MD, MPH

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Importance: Preclinical and preliminary human evidence suggests that metformin, a first-line treatment for type 2 diabetes, reduces inflammation, preserves cartilage, and improves knee pain in knee osteoarthritis.

Objective: To evaluate the effects of metformin on knee pain at 6 months in participants with symptomatic knee osteoarthritis and overweight or obesity.

Design, setting, and participants: Community-based randomized, parallel-group, double-blind, placebo-controlled clinical trial that used telemedicine to recruit and follow up participants remotely. Individuals with knee pain for 6 months or longer, a pain score greater than 40 mm on a 100-mm visual analog scale (VAS), and body mass index of 25 or higher were recruited from the community through local and social media advertisements in Victoria, Australia, between June 16, 2021, and August 1, 2023. Final follow-up occurred on February 8, 2024.

Interventions: Participants were randomly assigned to receive either oral metformin, 2000 mg/d (n = 54), or identical placebo (n = 53) for 6 months.

Main outcomes and measures: The primary outcome was change in knee pain, measured using a 100-mm VAS (score range, 0-100; 100 = worst; minimum clinically important difference = 15) at 6 months.

Results: Of 225 participants assessed for eligibility, 107 (48%) were randomized (mean age, 58.8 [SD, 9.5] years; 68% female) and assigned to receive metformin or placebo. Eighty-eight participants (82%) completed the trial. At 6 months, the mean change in VAS pain was -31.3 mm in the metformin group and -18.9 mm in the placebo group (between-group difference, -11.4 mm; 95% CI, -20.1 to -2.6 mm; P = .01), corresponding to an effect size (standardized mean difference) of 0.43 (95% CI, 0.02-0.83). The most common adverse events were diarrhea (8 [15%] in the metformin group and 4 [8%] in the placebo group) and abdominal discomfort (7 [13%] in the metformin group and 5 [9%] in the placebo group).

Conclusions and relevance: These results support use of metformin for treatment of symptomatic knee osteoarthritis in people with overweight or obesity. Because of the modest sample size, confirmation in a larger clinical trial is warranted.

Author/s:

Feng Pan, Yuanyuan Wang, Yuan Z Lim, Donna M Urquhart

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