Duration Of Metformin Therapy Research Articles

Long-term use of metformin and Alzheimer's disease: beneficial or detrimental effects.

Alzheimer's disease (AD) is the most common neurodegenerative disease characterized by extracellular deposition of amyloid beta (Aβ) leading to cognitive decline. Evidence from epidemiological studies has shown the association between type 2 diabetes mellitus (T2DM) and the development of AD. T2DM and peripheral insulin resistance (IR) augment the risk of AD with the development of brain IR with inhibition of neuronal insulin receptors. These changes impair clearance of Aβ, increase secretion of Aβ1-42, reduce brain glucose metabolism, and abnormal deposition of Aβ plaques. Insulin-sensitizing drug metformin inhibits aggregation of Aβ by increasing the activity of the insulin-degrading enzyme (IDE) and neprilysin (NEP) levels. Additionally, different studies raised conflicting evidence concerning long-term metformin therapy in T2DM patients, as it may increase the risk of AD or it may prevent the progression of AD. Therefore, the objective of this review was to clarify the beneficial and detrimental effects of long-term metformin therapy in T2DM patientsandrisk of AD. Evidence from clinical trial studies revealed the little effect of metformin on AD. Various animal studies showed that metformin increases Aβ formation by activation of amyloid precursor protein (APP)-cleaving enzymes with the generation of insoluble tau species. Of note, the metformin effect on cognitive function relative to AD pathogenesis is mostly assessed in animal model studies. The duration of metformin therapy was short in most animal studies, this finding cannot apply to the long-term duration of metformin in humans. Therefore, large-scale prospective and comparative studies involving long-term metformin therapy in both diabetic and non-diabetic patients are required to exclude the effect of T2DM-induced AD.

Influence of metformin intake on serum vitamin B12 levels in patients with type 2 diabetes mellitus.

To describe the prevalence of vitamin B12 deficiency among Jordanian patients with type 2 diabetes mellitus treated with metformin and to compare the findings with those who did not receive metformin. Total 155 patients with type 2 diabetes mellitus, aged between 48 and 82 years were enrolled in the current study. They were divided into two groups; the first (n = 120) was treated with metformin while the second (n = 35) was not. Patients' demographics (age, gender, duration of type 2 diabetes mellitus, smoking status), medication parameters (daily dosage and duration of metformin therapy), and biochemical parameters (hemoglobin level, mean corpuscular volume (MCV), serum vitamin B12, and folate level) were recorded. Definite deficiency was defined as serum vitamin B12 levels of < 150 pg/ml, whereas < 200 pg/ml indicated possible deficiency. The mean serum ± standard deviation (SD) vitamin B12 level was significantly lower in patients who were treated with metformin (268.5 ± 35.8 vs. 389.5 ± 29.8 pg/ml, p = 0.029). The metformin group had significantly higher prevalence of definite deficiency (32% vs. 9%, p < 0.02) and possible deficiency (48% vs. 30%, p < 0.02). Within the metformin group, the mean serum ± SD vitamin B12 level was significantly lower in those on high dosage (175.2 ± 30.5 vs. 315.6 ± 37.8 pg/ml, p < 0.001). MCV (μm3) levels ± SD were higher in the metformin group (87.5 ± 2.9 vs. 83.7 ± 2.4) with no statistical significance. There is a significant association between metformin intake and vitamin B12 deficiency. Serum vitamin B12 levels should be checked by physicians and serial monitoring is necessary in patients who are treated with metformin.

Effect and Safety of Adding Metformin to Insulin Therapy in Treating Adolescents With Type 1 Diabetes Mellitus: An Updated Meta-Analysis of 10 Randomized Controlled Trials.

BackgroundThe role of metformin in the treatment of adolescents with type 1 diabetes mellitus (T1DM) remains controversial. We conducted this updated meta-analysis to generate a comprehensive assessment regarding the effect and safety of metformin in treating adolescents with T1DM.MethodsWe systematically searched PubMed, Embase, and the Cochrane Central Registry of Controlled Trials (CENTRAL) from their inception to November 2021 to identify randomized controlled trials evaluating the efficacy of metformin in the treatment of adolescents with T1DM. The primary outcome was the HbA1c level, and secondary outcomes included the body mass index (BMI), total insulin daily dose (TIDD) (unit/kg/d), hypoglycemia events, diabetes ketoacidosis (DKA) events, and gastrointestinal adverse events (GIAEs). Statistical analysis was conducted using RevMan 5.4 and STATA 14.0.ResultsTen studies enrolling 539 T1DM adolescents were included. Results suggested that metformin significantly decreased the HbA1c level at 12 months (mean difference [MD])=-0.50, 95% confidence interval [CI]=-0.61 to -0.39, P < 0.01); BMI (kg/m2) at 3 months (MD=-1.05, 95%CI=-2.05 to -0.05, P=0.04); BMI z-score at 6 months (MD=-0.10, 95%CI=-0.14 to -0.06, P<0.01); and TIDD at 3 (MD=-0.13, 95%CI=-0.20 to -0.06, P<0.01), 6 (MD=-0.18, 95%CI=-0.25 to -0.11, P<0.01), and 12 (MD=-0.42, 95%CI=-0.49 to -0.35, P<0.01) months but significantly increased the risk of hypoglycemia events (risk ratio [RR]=3.13, 95%CI=1.05 to 9.32, P=0.04) and GIAEs (RR=1.64, 95%CI=1.28 to 2.10, P<0.01). For remaining outcomes at other time points, no statistical difference was identified. Sensitivity analysis confirmed the robustness of all pooled results.ConclusionsThe use of metformin might result in decreased BMI (kg/m2), BMI z-score, and TIDD and increased risk of hypoglycemia events and GIAEs in adolescents with T1DM. However, future studies are required to further confirm the optimal dose and duration of metformin therapy.

Vitamin B12 Deficiency in Patients with Diabetes on Metformin: Arab Countries.

Background: Diabetes is a global pandemic, especially in Arab countries. Aim: The goal of this study was to review the published studies that were conducted to determine the relationship between metformin treatment for type 2 diabetes mellitus (T2DM) and vitamin B12 deficiency and to identify possible complications in this relationship. Methods: I searched for all relevant studies published in English before 2020 on the PubMed and Web of Knowledge databases using the following terms: “metformin”, “vitamin B12”, “neuropathy”, “diabetes mellitus”, and Middle Eastern countries. Results: Eleven studies were included in this review which indicated an association between taking metformin and B12 deficiency in patients with T2DM in Arab countries. This B12 deficiency was found to be negatively associated with the dose and duration of metformin therapy. The physician’s knowledge of current ADA recommendations regarding supplementation with and screening of the B12 level for T2DM patients on metformin was also found to have an effect. Conclusion: Metformin therapy is associated with B12 deficiency among people with T2DM in Arabic countries. Thus, diabetes must be managed in compliance with current guidelines and recommendations, and B12 levels must be routinely monitored, particularly in those who have been long-term takers of metformin, to ensure the suitable management of diabetes and its complications.

Correlation between secondary hyperparathyroidism and comorbid disorders among the Chornobyl NPP accident survivors

Background. Endocrine comorbidity, a concomitant radiation injury of several endocrine glands, is a topical issue in radiation medicine. The purpose of the study was to establish a correlation of secondary hyperparathyroidism with thyroid and pancreatic disorders among the Chornobyl nuclear power plant (NPP) accident survivors. Materials and methods. A blind sample (n = 60) of subjects treated at the radiation endocrinology department in 2019 was selected for the study. Study sample included the Chornobyl NPP accident survivors (group 1, n = 40) and patients not exposed to radiation (group 2, n = 20). The average age of people was 60.2 ± 9.8 years. Decompensation of type 2 diabetes was the most common cause for hospital admission (48.3 %), decompensation of hypothyroidism was in second place (46.7 %). Research methods: clinical, instrumental, laboratory, statistical. Results. Incidence of the increased risk of vitamin D deficiency and excessive parathyroid hormone production in the Chornobyl NPP accident survivors was somewhat higher than in individuals not exposed to radiation (81.08 and 78.12 %; χ2 = 0.257, p = 0.612; 31.12 and 28.08 %; χ2 = 0.462, p = 0.319, respectively). Using a multivariate analysis, the reliable model was obtained confirming the relationship of increased parathyroid hormone level and early subclinical signs of the target organ damage (F = 4.294; p = 0.042), which proves the relevance of using clinical questionnaires. A reliable positive correlation was found between the vitamin D and free thyroxine levels (r = 0.729; p = 0.001), and negative one was found with the thyroid-stimulating hormone content (r = –0.803; p = 0.001). In the Chornobyl NPP accident survivors with type 2 diabetes, a decreased vitamin D concentration correlated with an increased duration of metformin therapy (r = –0.421; p = 0.001) and body mass index (r = –0.787; p = 0.001). It was found that the parathyroid hormone level increases along with the duration of type 2 diabetes and an increase in creatinine clearance (r = 0.724; p = 0.001, and r = 0.799; p = 0.001). Conclusions. Vitamin D deficiency has a negative effect on the course of comorbid disorders (type 2 diabetes and hypothyroidism) and excessive production of parathyroid hormone.

Metformin Usage Index and assessment of vitamin B12 deficiency among metformin and non-metformin users with type 2 diabetes mellitus.

The present study aimed to evaluate the combined effect of both dose and duration of metformin therapy on vitamin B12 levels in patients with type 2 diabetes mellitus (T2D). We recruited 2887 patients with T2D between January 2018 and November 2019 and categorized them into two groups (metformin and non-metformin users) matched for age, mean duration of diabetes, and BMI. We calculated the "Metformin Usage Index" (MUI) which was defined as the product of the dose of metformin (mg) used and its duration divided by 1000. Vitamin B12 levels were compared between the two groups, and its association with MUI was assessed using correlation and multistep logistic regression analyses. Vitamin B12 levels < 200pg/ml and between 200 and 300pg/ml were noted among 24.5% and 34.5% metformin users, respectively; this was significantly higher than among non-metformin users (17.3% and 22.6%, respectively) [P < 0.001]. Overall, a vitamin B12 level < 300pg/ml was found in 52.2% of the subjects. There was a significant association between an MUI > 5 and a high risk of vitamin B12 deficiency [P < 0.01]. The highest risk was observed among patients with an MUI > 15 [odds ratio (OR) 6.74, 95% CI 4.39-10.4] followed by patients with an MUI > 10 (OR 5.12, 95% CI 3.12-8.38). The MUI can be employed as a risk assessment tool for evaluation of vitamin B12 deficiency in patients with T2D. Further prospective studies are required to determine the MUI thresholds in populations with good nutritional statuses and low prevalence of vitamin B12 deficiency.

Vitamin B12 Deficiency in Diabetic Patients on Metformin Therapy: A cross-sectional study from Oman.

ObjectivesThis study aimed to determine the prevalence of vitamin B12 deficiency amongst diabetic patients on metformin therapy.MethodsThis cross-sectional study was conducted at general clinics at the University Health Center and diabetes outpatient clinics at Sultan Qaboos University Hospital, Muscat, Oman, between January and December 2017. All Omani adults who were diagnosed with type 2 diabetes mellitus and took metformin were invited to participate in the study. The variables included in this study were age, gender, duration of diabetes, dose and duration of metformin therapy, haemoglobin and glycosylated haemoglobin level.ResultsA total of 248 subjects were included (response rate = 95.4%) of which 26 (10.5%) were vitamin B12 deficient and 53 (21.4%) were borderline deficient. The mean daily dose of metformin was highest among vitamin B12 deficient group (1,981 ± 222 mg; P = 0.004).ConclusionThe prevalence of vitamin B12 deficiency is considerable among diabetic patients on metformin therapy. Further research is needed to confirm the need for routine screening and monitoring.

Metformin reduces risk of benign nodular goiter in patients with type 2 diabetes mellitus

Background Whether metformin might affect the risk of benign nodular goiter in patients with type 2 diabetes mellitus has not been investigated. Methods Patients with new-onset type 2 diabetes mellitus during 1999-2005 were enrolled from Taiwan's National Health Insurance database. Analyses were conducted in a propensity score matched-pairs of 20,048 ever users and 20,048 never users of metformin. The patients were followed until December 31, 2011, for the incidence of benign nodular goiter. Hazard ratios were estimated by Cox regression incorporated with the inverse probability of treatment weighting using the propensity score. Results Among the never users and ever users of metformin, 392 and 221 cases were diagnosed of benign nodular goiter during follow-up, with incidence of 457.88 and 242.45 per 100,000 person-years, respectively. The overall hazard ratio for ever versus never users was 0.527 (95% confidence interval: 0.447-0.621). When cumulative duration of metformin therapy was divided into tertiles, the hazard ratios for the first ( 57.3 months) tertiles were 0.815 (0.643-1.034), 0.648 (0.517-0.812) and 0.255 (0.187-0.348), respectively. Sensitivity analyses estimating the overall hazard ratios for patients enrolled in each specific year from 1999 to 2005 consistently showed a lower risk of benign nodular goiter among users of metformin. Conclusion Metformin use is associated with a lower risk of benign nodular goiter in patients with type 2 diabetes mellitus.

Vitamin B12 deficiency in type 2 diabetic patients on metformin: a cross-sectional study from South-Western part of Ghana

ABSTRACTIntroduction: Metformin is the most widely administered anti-diabetic medication among type 2 diabetes mellitus (T2DM) patients. However, metformin induces vitamin B12 malabsorption which may increase the risk of vitamin B12 deficiency among T2DM patients. We determined the prevalence of vitamin B12 deficiency and related risk factors among Ghanaian T2DM patients on metformin therapy.Methods: This cross-sectional study recruited 196 T2DM patients attending the outpatient diabetic clinic at the Effia Nkwanta Regional Hospital, Ghana. Fasting venous blood was collected for biochemical analysis. Vitamin B12 deficiency was defined as serum B12 <100 pg/ml and methylmalonic acid (MMA) ≥ 0.4µmol/L.Results: The prevalence of vitamin B12 deficiency based on serum vitamin B12, MMA, and the combination of both methods were 32.1%, 14.8%, and 14.3%, respectively. Longer duration of metformin use [5-9 years; aOR= 2.83, 95% CI (1.03-7.81), p=0.045 and ≥10 years; aOR= 4.17, 95% CI (1.41-12.33), p=0.010], higher daily dose of metformin [1000-2000 mg/day; aOR= 1.34, 95% CI (0.25-2.74), p=0.038 and >2000 mg/day; aOR= 1.13, 95% CI (0.39-2.97), p=0.047], and very high body fat [aOR= 2.98, 95% CI (1.47-6.05), p=0.020] were significantly associated with increased odds of vitamin B12 deficiency. For daily dose of metformin, a cutoff value of 1500 mg/day presented with a sensitivity, specificity, and AUC of 71.4%, 40.1%, and 0.54 (95% CI, 0.53-0.54), respectively, in predicting vitamin B12 deficiency. A ≥ six (6) years duration of metformin therapy presented with a sensitivity, specificity, and AUC of 70.4%, 62.9%, and 0.66 (95% CI, 0.57-0.75), respectively, in predicting vitamin B12 deficiency.Conclusion: Vitamin B12 deficiency is high among T2DM patients on metformin therapy in Ghana. There is the need for regular monitoring of vitamin B12 levels especially in T2DM patients on metformin daily dose of ≥ 1500 mg for duration of therapy ≥ 6 years.

Serum Vitamin B12 and Homocysteine Levels in Type 2 Diabetic Patients with and without Metformin Therapy

Background: Vitamin B12 (cobalamin) is an essential micronutrient necessary for DNA methylation and plays role in lipid metabolic reactions. Metformin is the first therapeutic choice for T2DM management. Prolonged use of metformin causes vitamin B12 deficiency due to poor absorption by interfering with calcium-based vitamin B12 absorption. Vitamin B12 deficiency leads to elevated homocysteine levels. The aim of this study was to evaluate serum vitamin B12 and homocysteine levels in type 2 diabetic patients with and without metformin therapy. Methods: A cross-sectional study was conducted on two hundred and thirty diabetic patients (180 males and 50 females). Their ages ranged from (30 - 60 years) living in Saudia Arabia at Al-Madinah Al-Monawarah. Patients were selected at outpatients clinics of Islamic University Medical Center during follow up at internal medicine and endocrinology clinic. The included patients were diagnosed with type 2 diabetes mellitus according to American Diabetes Association (ADA) Criteria. The included patients were categorized into two groups according to treatment with metformin drug. Laboratory measurements included serum level of vitamin B12, serum total homocysteine, serum fasting glucose and serum folate. Blood EDTA samples were used to measure HbA1c and MCV. Neurological examinations were performed to detect presence of peripheral neuropathy using Toronto Clinical Neuropathy Score (TCSS), which is a validated and reliable scale for the diagnosis and staging of diabetic polyneuropathy. Results: There were no statistical differences between the two groups as regard (age, sex, smoking, weight, BMI, systolic blood pressure, diastolic blood pressure, fasting blood glucose, Folate and MCV). There were statistical differences between the two groups as regard (duration of diabetes, duration of metformin therapy, dose of metformin, Serum homocystein and HbA1c). The mean of vitamin B12 (pg/mL) of group 1 (312.65 ± 92.28) was lower than that of group 2 (381.55 ± 88.04). In group 1 number of patients with normal vitamin B12 was 116 out of 150 (77.3%) and number of patients with deficient vitamin B12 was 34 out of 150 (22.7%). In group 2 number of patients with normal vitamin B12 was 72 out of 80 (90%) and number of patients with deficient vitamin B12 was 8 out of 80 (10%). Regarding neuropathy; in group 1 113 patients (75.3%) had no neuropathy, 24 patients (16%) had mild neuropathy and 13 patients (8.7%) had moderate neuropathy. In group 2, 71 patients (88.8%) had no neuropathy, 7 patients (8.7%) had mild neuropathy and 2 patients (2.5%) had moderate neuropathy. In conclusion, in our study, the prevalence of vitamin B12 deficiency was higher in metformin users than in non-metformin users. There was an association between vitamin B12 deficiency and the dose and duration of metformin use. There was also an increase in homocysteine level due to vitamin B12 deficiency. Therefore, we recommend routine screening for serum vitamin B12 and homocysteine in individuals with T2DM who take daily metformin doses higher than 2000 mg, or for a duration exceeding 4 years.

Dipeptidyl Peptidase-4 Inhibitors versus Other Antidiabetic Drugs Added to Metformin Monotherapy in Diabetic Retinopathy Progression: A Real World-Based Cohort Study.

BackgroundTo investigate the effects of dipeptidyl peptidase-4 inhibitor (DPP4i) as add-on medications to metformin on progression of diabetic retinopathy (DR) in patients with type 2 diabetes mellitus, compared with sulfonylurea (SU) or thiazolidinedione (TZD).MethodsWe identified 4,447 patients with DPP4i, 6,136 with SU, and 617 with TZD in addition to metformin therapy from the database of Korean National Health Insurance Service between January 2013 and December 2015. Cox proportional hazards regression models were used to calculate hazard ratios (HRs) for DR progression. The progression of DR was defined by the procedure code of panretinal photocoagulation, intravitreal injection or vitrectomy; or the addition of diagnostic code of vitreous hemorrhage, retinal detachment, or neovascular glaucoma.ResultsThe age and sex-adjusted HR of DR progression was 0.74 for DPP4i add-on group compared with SU add-on group (95% confidence interval [CI], 0.62 to 0.89). This lower risk of DR progression remained significant after additional adjustments for comorbidities, duration of metformin therapy, intravitreal injections and calendar index year (HR, 0.80; 95% CI, 0.66 to 0.97).ConclusionThis population-based cohort study showed that the use of DPP4i as add-on therapy to metformin did not increase the risk of DR progression compared to SU.

Relationship of Vitamin B12 and Homocysteine Status with Nephropathy and Neuropathy in Metformin-Treated Patients with Type 2 Diabetes

Limited evidence suggests that both vitamin B12 (B12) and homocysteine (Hcy) status are impacted by metformin use and may be associated with diabetes complications. The goal of this research project was to assess the cross-sectional association between B12 and Hcy status and kidney function and neuropathy among patients with type 2 diabetes (T2D) taking metformin. Adult patients in an academic primary care clinic (n = 52; mean age = 53 ± 12.5 years; female 56%; African American 70%) with T2D (mean duration = 9.8 year) and taking metformin (mean duration = 9.2 year) provided informed consent and had blood and urine specimens drawn for: A1c, B12, Hcy, serum creatinine (sCr), urine albumin/creatinine ratio, and eGFR. Neuropathy was assessed using the validated Michigan Neuropathy Screening Instrument. Mean B12 and Hcy levels were 568.7pg/ml and 12.85 µmol/L, respectively. Serum B12 was significantly correlated with Hcy (r = -0.3, p = 0.035) and with A1c (r = 0.36, p = 0.01). Hcy was significantly correlated with both sCr (r = 0.70: p = 0.0001) and eGFR (r = -0.68; p = 0.0001). While B12 was not directly correlated with either diabetes duration or duration of metformin therapy, the correlation of B12 with total metformin exposure (dose x years) approached significance (r = -0.26; p = 0.06). There was no relationship of either B12 or Hcy with neuropathy scores. The bivariate relationship of B12 and Hcy to renal function measures was not different in patients with a diabetes duration of less than 10 years vs. 10 or more years. Consistent with previous studies our findings suggest that B12 status, in addition to correlating with renal function, correlated with glycemic control. Periodic measurement of B12 status should be considered in metformin-treated patients with T2D. Disclosure S. Patil: None. R. Pawlak: None. A. Thombare: None. R. Baltaro: None. K. Hicks: None. D.M. Cummings: None.

Metformin and Risk of Hepatocellular Carcinoma in Taiwanese Patients with Type 2 Diabetes

Background: Whether metformin may reduce hepatocellular carcinoma (HCC) risk requires confirmation. Methods: Newly diagnosed type 2 diabetes patients during 1999-20with 2 or more prescriptions of antidiabetic drugs were enrolled from the Taiwan’s National Health Insurance. A total of 173917 ever users and 21900 never users of metformin were identified (unmatched cohort). A 1:1 matched-pairs cohort of 21900 ever users and 21900 never users based on propensity score was created. Hazard ratios were estimated by Cox regression incorporated with the inverse probability of treatment weighting using PS. Additionally, the interactions with aspirin and statin were evaluated. Results: In the unmatched cohort, 619 never users and 2642 ever users developed HCC, with respective incidence of 668.0 and 330.7 per 100,000 person-years and overall hazard ratio of 0.49 (95% confidence interval: 0.45-0.54). The hazard ratio for the first (&amp;lt;25.7 months), second (25.7-56.9 months) and third (&amp;gt;56.9 months) tertile of cumulative duration of metformin therapy was 0.89 (0.81-0.98), 0.50 (0.46-0.56) and 0.23 (0.21-0.26), respectively. Analyses in the matched cohort showed an overall hazard ratio of 0.69 (0.62-0.78) and the hazard ratio for the respective tertile was 1.28 (1.10-1.50), 0.68 (0.57-0.82) and 0.35 (0.29-0.44). A significant interaction with metformin was observed for aspirin and statin. Conclusions: Metformin is associated with a reduced risk of HCC in a dose-response pattern. Users of both metformin and aspirin or statin have the lowest risk. Disclosure C. Tseng: None.

Serum B12 Levels in Type II Diabetics on Metformin Therapy and its association with Clinical Neuropathy

Background: Metformin use in type II DM has also been known to cause B12 deficiency in as reported many studies. Iatrogenic neuropathy caused by Metformin induced B12 deficiency can add to burden of peripheral neuropathy that already exists in diabetic patients. Aims and Objectives: 1)To determine the serum vitamin B12 levels in patients of type II DM on metformin therapy and compare it with those not on metformin therapy; 2) To correlate serum vitamin B12 levels with dose and duration of metformin therapy; 3) To investigate association between peripheral neuropathy and serum vitamin B12 levels. Method: The present two year hospital based cross sectional study enrolled total 132 cases of type 2 diabetes mellitus and divided into two groups, (metformin group 70 and non-metformin group 62). Serum vitamin B12 levels were measured in all patients. Toronto clinical scoring system (TCSS) and nerve conduction velocity (NCV) tests were used to assess peripheral neuropathy. The correlations of vitamin B12 levels with Toronto clinical score, nerve conduction studies, cumulative dose and duration of metformin therapy was done. Results: The serum vitamin B12 levels were significantly lower in patients who consumed metformin (292.64 152.82 pg/ml) as compared to non-metformin, (406.91 126.59 pg/ml) group. There was a significant negative correlation of serum vitamin B12 levels with cumulative dose and duration of metformin therapy. The incidence of neuropathy by TCSS and NCV test was significantly higher in metformin group with a positive correlation with cumulative dose and duration of metformin and a negative correlation with serum vitamin B12 levels. Conclusion: Metformin use is significantly associated with decrease in vitamin B12 levels and increased incidence of neuropathy, this is dependent on dose and duration of metformin therapy.

An observational study of vitamin b12 levels and peripheral neuropathy profile in patients of diabetes mellitus on metformin therapy

MethodsA descriptive, observational study was completed in a tertiary care hospital between November 2014 and March 2016. Fifty consecutive patients of Type 2-Diabetes Mellitus who had been on metformin therapy for at least three months were included in our study. Several Parameters were compared with vitamin B12 levels and severity of peripheral neuropathy (using Toronto Clinical Scoring System (TCSS) and Nerve Conduction Velocity). These included the duration of diabetes, duration of metformin usage, dietary history, and HbA1c levels. Definite B12 deficiency was defined as B12<150pg/ml and possible B12 deficiency as <220pg/ml. ResultsIn our study, we found a negative correlation between duration of metformin use and Vitamin B12 levels(r=−0.40). The mean Vitamin B12 levels seen in our study was 212.3pg/mL. There is a positive correlation between the duration of metformin therapy and peripheral neuropathy (r=0.40). The mean TCSS score was 6.8. The percentage of patients with mild neuropathy was 28%, with moderate neuropathy was 20% and severe neuropathy in 12% of the patients. The average duration of metformin use in patients without peripheral neuropathy was 5.5yrs whereas the average length of metformin use in patients with peripheral neuropathy was 10.4 yrs. ConclusionPatients on long-term metformin therapy are at a high risk for Vitamin B12 deficiency and peripheral neuropathy. Interval Screening for peripheral neuropathy is recommended for patients on metformin even if Vitamin B12 levels appear to be normal.

Abstract 2296: Metformin reduces colon cancer risk in patients with type 2 diabetes: a retrospective cohort analysis

Abstract Background: The effect of metformin on colon cancer is rarely investigated in Asian populations. Methods: This is a retrospective cohort study. Patients with newly diagnosed type 2 diabetes during 1999-2005 were recruited from Taiwan’s National Health Insurance. A 1:1 propensity score matched-pair sample of 16314 ever users and 16314 never users of metformin were followed until December 31, 2011. Cox regression incorporated with the inverse probability of treatment weighting using propensity score was used to estimate hazard ratios. Results: The incidence of colon cancer was 272.04 and 392.44 per 100,000 person-years, respectively, in ever and never users. The overall hazard ratio (0.691, 95% confidence interval: 0.578-0.826) suggested a significantly lower risk in metformin users. While compared to never users, the hazard ratio (95% confidence interval) for the first (&amp;lt;20.00 months), second (20.00-45.20 months) and third (&amp;gt;45.20 months) tertile of cumulative duration of metformin therapy was 1.455 (1.165-1.816), 0.683 (0.526-0.885) and 0.224 (0.152-0.331), respectively. The protective effect of metformin on colon cancer was not affected by the use of aspirin and statin or the infection of Helicobacter pylori in additional analyses. Conclusions: Metformin reduces colon cancer risk in patients with type 2 diabetes. The protective effect is more remarkable when the cumulative duration is more than 20 months. Citation Format: Chin-Hsiao Tseng. Metformin reduces colon cancer risk in patients with type 2 diabetes: a retrospective cohort analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2296. doi:10.1158/1538-7445.AM2017-2296

Vitamin B12 Deficiency in Diabetic Patients on Chronic Metformin Therapy

Introduction: Since its approval and universal acknowledgement in the 1990's as a first line agent for the treatment of Diabetes Mellitus Type II, studies have shown vitamin B12 deficiency to be a complication of chronic metformin therapy. Despite this awareness and few studies aimed at the general population, a systematic assessment of the prevalence of vitamin B12 deficiency in Type II diabetics on metformin in the veteran population has not been performed. Methods: A retrospective data analysis at a VA Hospital from 2002-2012 was performed which included 3844 diabetic patients on metformin who had B12 levels drawn while on metformin. Vitamin B12 deficiency was defined as B12 ≤ 218 pg/mL and further subdivided into moderate (218-175 pg/mL) and severe (1500 mg/day). The duration of metformin therapy was categorized as short (4 years) and long (>4 years). Results: Overall prevalence of B12 deficiency while on metformin therapy was 9.8 %. Only 38 % of the patients had baseline B12 levels checked prior to their becoming deficient. There was a significant difference when comparing B12 deficiency between control vs. metformin group (P < 0.0001 CI (2.5-10.6), OR 5.1, and Metformin vs. Insulin group P < 0.0001, CI (0.13-1.43), OR 11.6 (Table 1). There was a significant difference between short duration vs. long duration of metformin in regards to moderate vs. severe B12 deficiency (Table 2). In addition, there was a significant difference between low dose metformin group and high dose metformin group in regards to moderate vs. severe B12 deficiency (Table 2).Table 1: P value, Confidence Interval, and OR for Control vs. Metformin vs. Insulin.Table 2: Comparison of Duration and Dosing of Metformin therapy vs. B12 deficiencyConclusion: We report 9.8% overall prevalence of patients with B12 deficiency while on metformin. Compared to insulin-treated diabetics and non-diabetics, metformin group had significantly more patients with overt B12 deficiency (B12 < 218 pg/mL). Higher dose and longer duration appear to worsen the problem. B12 deficiency develops gradually and is frequently overlooked although it is easy to treat if suspected and managed in time. Our study highlights the lack of awareness of this important problem as evidenced by the small percentage of veterans that had undergone prior B12 testing (38%). Primary care providers and specialists need to be cognizant of the necessity of Vitamin B12 testing with chronic metformin therapy.

Vitamin B12 Deficiency in the Elderly using Metformin Long Term: Prevalence and Relationship to Putative Risk Factors

ABSTRACTAimTo determine the prevalence of vitamin B12 deficiency in elderly patients using metformin long term and to assess putative risk factors for reduced vitamin B12 concentrations.MethodPatients using metformin for more than 2 years admitted to or reviewed in the Repatriation General Hospital from June to December 2006 were enrolled in this cross‐sectional study. The prevalence of vitamin B12 deficiency and the association between vitamin B12 deficiency and putative risk factors were determined.Results60 patients were recruited. Of the 53 patients not taking vitamin B12 supplements, 8 (15%; 95%CI 7.2–28.1) were vitamin B12 deficient (83–148 pmol/L). 7 patients taking vitamin B12 supplements had statistically significantly higher serum vitamin B12 concentrations and decreased B12 deficiency. Daily metformin dose was associated with a statistically significant negative correlation with vitamin B12 concentration and was statistically higher in vitamin B12‐deficient patients. Duration of metformin therapy, age and use of proton pump inhibitors or calcium supplements were not statistically significantly associated with vitamin B12 concentration or deficiency.ConclusionElderly patients taking metformin should be monitored for vitamin B12 status, especially those on high doses of metformin. Vitamin B12, but not calcium, supplements should be considered to prevent or correct deficiency.

Effect of metformin on glycaemic control in type 2 diabetes in daily practice: a retrospective study

Introduction. Recently the UKPDS study revealed the potency of metformin therapy in obese type 2 diabetic patients. A retrospective study was performed to assess the efficacy of metformin therapy in improving metabolic control in everyday practice.Patients and methods. Type 2 diabetic patients were included if they met the following criteria: metformin had been added when the previous treatment failed to optimise glycaemic control expressed in HbA1c level; duration of metformin therapy had to be at least six months. Efficacy of metformin therapy, expressed as a decrease in HbA1c, was measured with a median follow-up of 32 (range 6–60) months. Variables were analysed using a paired t-test.Results. One hundred and sixty-three patients were treated with metformin. 98 patients were excluded, because of absence of an HbA1c value prior to treatment with metformin mainly (n=78). The mean HbA1c of included patients had decrerased 1.4% (p<0.001) after 6 months (n=65), 1.6% (p<0.001) after 24 months (n=45) and 1.5 (p<0.001) after 36 months (n=28). During follow-up there was no significant weight gain or loss.Conclusion. Metformin can be considered an effective treatment to improve glycaemic control in obese type 2 diabetic patients.