Metformin Use In Type Research Articles

Evaluating Physician Knowledge, Attitudes, and Practices in Screening and Supplementation for Vitamin B12 Deficiency in Type 2 Diabetes Patients Treated with Metformin.

Long-term metformin use in Type 2 Diabetes Mellitus (T2DM) patients is associated with Vitamin B12 deficiency. This study aims to evaluate physicians' knowledge, attitudes, and practices regarding Vitamin B12 screening and supplementation in this context. A survey was administered to physicians across various specialties in government hospitals and primary care centers in Riyadh, Saudi Arabia, from January 2019 to January 2020. The survey assessed their knowledge, attitudes, and practices concerning Vitamin B12 deficiency screening and supplementation. Of the 402 participating physicians, 94.0% (378 respondents) demonstrated sufficient knowledge about Vitamin B12 deficiency. However, 26.1% believed that Vitamin B12 supplementation does not necessitate screening. 55.7% did not prescribe Vitamin B12 prophylactically, 41.5% omitted neurological examinations in patients presenting with neuropathy, and 22.4% were unaware of the recommended Vitamin B12 supplement dose. Only 49.8% routinely screened for Vitamin B12 deficiency in symptomatic patients. Physicians with more extended years of experience showed significantly better knowledge about Vitamin B12 screening and supplementation (p<0.001). While most physicians were knowledgeable about Vitamin B12 deficiency and supplementation, a substantial gap in translating this knowledge into practice was observed. There is a critical need for institutional oversight to ensure adherence to American Diabetes Association (ADA) guidelines for Vitamin B12 screening and supplementation in T2DM patients on long-term metformin therapy.

Metformin administration in prevention of colorectal polyps in type 2 diabetes mellitus patients.

Colorectal polyps are frequently observed in patients with type 2 diabetes mellitus (DM), posing a significant risk for colorectal cancer. Metformin, a widely prescribed biguanidine drug for type 2 DM, has been suggested to have potential chemoprophylactic effects against various cancers. To explore the correlation between colorectal polyps and metformin use in type 2 DM patients. Type 2 DM patients were categorized into polyp and non-polyp groups. Following this, all patients were categorized into the type 2 DM-metformin, type 2 DM-non-metformin, and non-type 2 DM groups. Based on the baseline colonoscopy results, we performed pairwise comparisons of the incidence of colorectal polyps among the three groups. Additionally, we analyzed the relationship between colorectal polyps and the duration of metformin use and between the size and number of polyps and metformin use. Simultaneously, we focused on the specific pathological types of polyps and analyzed their relationship with metformin use. Finally, we compared the incidence of polyps between metformin and non-metformin groups according to the interval colonoscopy results. The rate of metformin use in patients with colorectal polyps was 0.502 times that of patients without colorectal polyps [odds ratio (OR) = 0.502, 95% confidence interval (CI): 0.365-0.689; P < 0.001]. The incidence of colorectal polyps did not differ significantly between the type 2 DM-metformin and non-type 2 DM groups (P > 0.05). Furthermore, the correlations between the duration of metformin use and the incidence of colorectal polyps and between the size and number of polyps and metformin use were not statistically significant (P > 0.05). Metformin use did not affect the incidence of colorectal polyps during interval colonoscopy (P > 0.05). Metformin use and colorectal polyp incidence in type 2 DM patients showed a negative correlation, independent of the hypoglycemic effect of metformin.

LACTIC ACIDOSIS IN TYPE 2DIABETES PATIENT WITH AND WITHOUT RENAL IMPAIRMENT TREATED WITH METFORMIN

Metformin is a widely used antihyperglycemic agent recommended by both the American Diabetes Association and the European Association for the Study of Diabetes as the first-line type 2 diabetes treatment in all patients receiving a new diagnosis, regardless of age Lactic acidosis (LA) is a rare event, with an estimated incidence of 4.3 cases per 100,000 person-years in metformin users LA is caused by the buildup of lactic acid in the bloodstream. It is characterized by an arterial lactate level ?5 mmol/L and a blood pH ?7.35, and occurs when oxygen levels in the body drop (hypoxia). The occurrence of LA in type 2 diabetes is of great concern because the mortality rate of LA can be as high as 50% .To determine whether the use of metformin in type 2 diabetic patients with various kidney functions is associated with an increased risk of lactic acidosis (LA). Lactic acidosis occurs in patients taking metformin who have renal failure. In our study, metformin was used in CKD stage 1 to 3b patients. Most of them were in stage 3. There is statistically significant association between stages of kidney disease and serum lactate level(P&lt;0.05) .There Is statistically significant association between stages of kidney disease and arterial blood gas analysis.

PSUN265 Metformin-Induced Severe Lactic Acidosis Requiring Urgent Dialysis Associated With Influenza A Infection in a Patient With Previous Preserved Renal Function: Case Report

Abstract Background Although rare, metformin-induced lactic acidosis it's a severe acute condition, that requires immediate recognition and management due to its high lethality. Clinical case Female, 70-years-old, presents to the E.R. with generalized malaise, weakness and myalgia for 4 days associated with diarrhea and vomits for 2 days. Denies fever or flu-like symptoms. History of hypertension and T2DM using metoprolol 100mg/day, perindopril 10mg/day, indapamide 2.5mg/day, amlodipine 5mg/day, linagliptin 5mg/day, rosuvastatin 10mg/day, gliclazide 120mg/day, aspirin 100mg/day, clonidine 0.3mg/day and metformin XR 1g/day. On clinical exam she was dehydrated and tachypneic with no other important findings. Laboratory showed glucose 31mg/dL, severe metabolic acidosis - pH 6,0; HCO3 5,4mmol/L; lactate 11.6mmol/L (n&amp;lt;1.6mmoL/L), acute renal failure KDIGO 3, creatinine 8.08mg/dL eGFR 5mL/min/1.73m2 (patient's baseline 0.9mg/dL), BUN 213mg/dL (n&amp;lt;50mg/dL), potassium 6.8mEq/L (3.5&amp;gt;n&amp;lt;5.1mEq/L), phosphor 14.9mg/dL (2.7&amp;gt;n&amp;lt;4.5mg/dL), chlorine 92mEq/L (98&amp;gt;n&amp;lt;107mEq/L), magnesium 1.7mg/dL (1.6&amp;gt;n&amp;lt;2.6mg/dL), calcium 0.95mmol/L (1.16&amp;gt;n&amp;lt;1.32mmol/L), and normal blood count. She was admitted to the ICU, hemodynamically stable with no need for vasoactive amine, breathing under nasal cannula and proceed with emergency hemodialysis. Acidosis was corrected after 6h of hemodialysis. Patient turned eupneic in room air and presented renal function improvement (BUN 44mg/dL; Creatinine 2.66mg/dL). She continued under intensive care and daily hemodialysis for another 4 days. The etiological investigation excluded glomerulopathies of rheumatological cause, blood cultures, serology for hepatitis, HIV and Dengue were all negative. However, respiratory viral panel was positive for influenza A. Although metformin serum dosage was not performed, renal function stability without the need for hemodialysis was only achieved after discontinuation of metformin. The main diagnostic hypothesis was metformin-induced severe metabolic acidosis. Finally, the patient was discharged on day 10, with stable renal function without hemodialysis (creatinine 2.19mg/dL eGFR 22mL/min/1.73m2) and no neurological deficits. The patient was referred to the endocrinologist and nephrologist to follow-up. Conclusion Metformin is affordable, safe and widely prescribed since the 50's. Although rare, metformin-induced lactic acidosis is a lethal toxicity, with identifiable risk factors that must be considered by prescribers. References Lazarus, Benjamin et al. "Association of Metformin Use With Risk of Lactic Acidosis Across the Range of Kidney Function: A Community-Based Cohort Study." JAMA internal medicine vol. 178,7 (2018): 903-910. doi: 10.1001/jamainternmed.2018.0292 Salpeter, Shelley R et al. "Risk of fatal and nonfatal lactic acidosis with metformin use in type 2 diabetes mellitus." The Cochrane database of systematic reviews vol. 2010,4 CD002967. 14 Apr. 2010, doi: 10.1002/14651858.CD002967.pub4 Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

Comparison of Serum Vitamin B12 Levels Among Drug-Naïve and Metformin-Treated Patients With Polycystic Ovary Syndrome.

Background Metformin is frequently prescribed for polycystic ovary syndrome (PCOS). There is a well-established causal relationship between metformin use in type 2 diabetes and vitamin B12 deficiency; such a relationship is seldom studied in PCOS. We conducted this study to compare vitamin B12 levels among newly diagnosed and metformin-treated patients with PCOS. Methodology This cross‑sectional comparative study was conducted from July 2021 to June 2022, among patients with PCOS attending a specialized endocrinology clinic of a tertiary hospital in Mymensingh, Bangladesh. A total of 50 patients newly diagnosed with PCOS and 52 with PCOS who had received metformin for at least six months were evaluated. The serum vitamin B12 level was measured by utilizing the chemiluminescent microparticle immunoassay principle. Results The new drug-naïve and metformin-treated subjects with PCOS had similar clinical and laboratory parameters except for the metformin group's lower hemoglobin levels and higher plateletcrit. Metformin receivers had lower serum vitamin B12 levels than the drug-naïve subjects (385.5 pg/mL [interquartile range, or IQR, 298.7-535.2] vs. 272.0 pg/mL [IQR 217.0-395.7];P< 0.001). The metformin group had higher frequencies of B12 deficiency and borderline deficiency (15.4% vs. 6% and 42.3% vs. 18%, respectively; P= 0.003). Conclusions This study observed lower serum B12 levels in PCOS patients using metformin than in the newly diagnosed ones. Large-scale data are needed to recommend routine periodic screening for B12 levels in metformin-treated PCOS.

Vitamin B12 Deficiency and Clinical Neuropathy with Metformin Use in Type 2 Diabetes.

Introduction: Type 2 diabetes (T2DM), which is more prevalent (more than 90% of all diabetes cases) and the main driver of the diabetes epidemic, now affects 5.9% of the world’s adult population, with almost 80% of the total in developing countries. At present, 537 million adults (20–79 years) are living with diabetes—1 in 10. This number is predicted to rise to 643 million by 2030 and 783 million by 2045. In India, reports show that 69.2 million people are living with diabetes (8.7%) as per 2015 data. Long-term metformin treatment is a known pharmacological cause of vitamin B12 (Vit B12) deficiency, as was evident within the first 10–12 years after it started to be used. Methods: This was a cross-sectional study conducted in the Postgraduate Department of Medicine in one of the tertiary hospitals in Kashmir. A total of 1600 consecutive patients with T2DM were taken for the study. Out of which 700 patients met the inclusion criteria. These 700 patients were divided into two groups: those taking metformin, and those who were not on metformin. Cumulative metformin doses were recorded in patients taking metformin, using history of dose and duration of treatment. Serum Vit B12 levels were taken for all patients. Based on the results of Vit B12 levels, patients were classified into normal levels (20 pmol/L), possible B12 deficiency (150–220 pmol/l), and definite deficiency (<150 pmol/L). Results: Our results depicted that patients on prolonged metformin therapy showed an increase in Vit B12 deficiency by 11.16%. The prevalence of clinical neuropathy in the metformin-exposed group was 45%, whereas, a prevalence of 31.8% was found in the non-metformin group. The mean age of patients with neuropathy was higher than those without neuropathy (59.01 ± 7.14 vs. 49.95 ± 7.47) (p-value < 0.514, statistically insignificant). Conclusions: In our study, we found that metformin use is associated with Vit B12 deficiency, which is dependent upon the cumulative dose of metformin. Importantly, prolonged metformin use is also associated with an increase in the prevalence of clinical neuropathy.

Prevalence of Vitamin B12 deficiency in Type II diabetic patients using metformin.

Objectives: To determine the prevalence of Vitamin B12 deficiency in type II diabetic patients using metformin. Study Design: Cross Sectional study. Setting: Endocrinology Unit Shalamar Hospital Lahore. Period: July to September 2017. Material &amp; Methods: All of our patients were having previously diagnosed type II diabetes and using metformin for more than six months. Using strict exclusion criteria, vitamin B12 levels of patients were measured and analyzed. Results: It was evident from the present study that 27.33% of type II diabetic patients using metformin were having vitamin B12 levels less than 150pg/ml. Furthermore, our study showed that smokers are more liable to develop vitamin B12 deficiency than the nonsmokers. Also, use of multivitamins (containing vitamin B12) had a protective role against vitamin B12 deficiency. Conclusions: Long term use of metformin in type II diabetic patients is strongly associated with Vitamin B12 deficiency, therefore endocrinologists and physicians should take into consideration this significant adverse effect of metformin and screen for vitamin B12 deficiency in diabetic population before starting metformin therapy.

English

BACKGROUND Metformin is considered as a cornerstone in the treatment of diabetes and is the most frequently prescribed first line therapy for individuals with T2DM. Metformin use in type 2 diabetes mellitus has shown to cause vitamin B12 (B12) deficiency. Besides these, B12 deficiency related neuropathy may mimic and/or aggravate the underlying diabetic neuropathy. Furthermore, there have been lack of consensus regarding the universal routine screening of serum B12 levels among metformin users with T2DM, and similar studies from India are also limited. So, we wanted to study the relationship between metformin use and serum B12 in T2DM patients. METHODS The study included a total of 104 subjects of which 52 are T2DM affected individuals who are only on metformin therapy for at least 3 months, served as cases and 52 are newly diagnosed T2DM age and sex matched individuals yet to be medically treated, served as controls. Their blood samples were collected to estimate vitamin B12 and other parameters. RESULTS The median B12 levels in cases 213.5 pg/mL (IQR 136.25-301.0) were found to be significantly lower (P &lt; 0.05) when compared to median levels of controls 240 pg/mL (IQR 214-303.25). B12 levels also showed a significant fall in their levels with increasing duration of T2DM. CONCLUSIONS Metformin induced vitamin B12 deficiency plays a major role in developing life risks in T2DM patients. Routine screening and supplementation of B12 may be required in T2DM patients KEYWORDS Metformin, Type 2 Diabetes Mellitus, Vitamin B12

In CKD, dapagliflozin reduced a composite of eGFR decline, end-stage kidney disease, or CV or renal mortality.

Heerspink HJ, Stefánsson BV, Correa-Rotter R, et al. Dapagliflozin in patients with chronic kidney disease. N Engl J Med. 2020;383:1436-46. 32970396.

Serum vitamin B12 and homocysteine levels in type 2 diabetes patients on metformin

Background: Metformin is reported to induce vitamin B12 deficiency, however India data is limited. The present study was conducted to assess the vitamin B12 and homocysteine levels among type 2 diabetes mellitus patients taking metformin.Methods: The present observational study included 60 patients with diabetes mellitus, 30 patients on metformin therapy (at least 6 months) and 30 patients not on metformin use. Laboratory investigations were sent for vitamin B12, homocysteine and HbA1c.Results: Mean vitamin B12 level was 159.67±95.73 and 510.73±206.18 pmol/l in the metformin and non-metformin group respectively (p value &lt;0.001). Serum homocysteine levels were found to significantly higher in the metformin group as compared to non-metformin group (17.39±4.97 vs 14.43±2.43 µmol/l, p value &lt;0.01). Folate levels were similar in the two study groups (22.71±3.67 vs 27.54±2.83 mmol/L). Haemoglobin A1c levels were significantly higher in the metformin group as compared to non-metformin group (7.85±0.97 vs 7.25±0.80 respectively). Triglycerides, high density lipoprotein and total cholesterol levels were found to be similar between the two study groups. However, low density lipoproteins were significantly higher in the metformin group as compared to the non-metformin group (3.7±0.92 vs 3.4±0.86 mmol/l).Conclusions: Our results show metformin use in type 2 diabetes mellitus patients was associated with significantly lower vitamin B12 levels and significantly high homocysteine levels.

Association of B12 levels with metformin use in type 2 diabetes patients

Association of B12 levels with metformin use in type 2 diabetes patients

Science, Medicine, and the Anesthesiologist

Science, Medicine, and the Anesthesiologist

MON-621 Prescription Analysis Shows High Metformin Use and Acceptance in a Diabetes Specialty Centre in Eastern India

Background and aims: Achieving glycemic goals is crucial in the overall management of diabetes. Selecting the right medication for the individual patient is of paramount importance in the present day’s patient centric glucose control. Metformin is the first line and gold standard antihyperglycemic agent that can be offered to type 2 diabetics. Addition of a second or third agent or insulin should be considered in those whose HbA1c remains high despite the up-regulated metformin dose or those who do not tolerate metformin. We aimed to find the pattern of metformin use in type 2 diabetic subjects in a diabetes specialty centre in coastal Odisha. Materials and methods: This observational study was conducted in a diabetes setup in coastal Odisha in June 2018. After obtaining consent from patients, authors looked into the prescriptions of all type 2 diabetic adults. Subjects who were prescribed metformin (in any dose) were enrolled in the study. Those with established nephropathy, coronary artery disease, stroke or cancers were excluded. Results:There were 802 footfalls noted during the study period, of which 723 metformin taking participants (298 females, 41.2%) were considered for analysis (79 persons were excluded: not meeting inclusion criteria/ not willing to participate/ history of nephropathy/ CAD/ stroke). Mean age, diabetes duration, FPG, HbA1c, serum creatinine, eGFR of the study population were 51.6±10.6 years, 11.9±11.2 years, 138.7±51.7 mg/dl, 7.8±2.1%, 0.93±0.29 mg/dl and 96.5±11.1ml/min respectively. Patients were prescribed metformin in various doses, i.e., 500mg (42 patients, 5.8%), 850mg (47 patients, 6.5%), 1000mg (396 patients, 54.8%), 1500mg (13 patients, 1.8%), 1700mg (86 patients, 11.9%) and 2000mg (130 patients, 18.0%), and 2500mg (9 patients, 1.2%). Metformin was prescribed as monotherapy (n=34, 4.7%) or along with other OADs (n=589, 81.5%) or in combination with insulin (n=178, 24.6%). Retrospective analysis of the medical records and further questioning revealed that gastric intolerance was the commonest reason for withdrawal of metformin in otherwise eligible subjects. Conclusion: Metformin was the most commonly prescribed antidiabetic drug and the daily dose of more than 85% of the metformin administered individuals was 1000mg or above.

576-P: Prevalence of Vitamin B12 Deficiency and Clinical Neuropathy with Metformin Use in Type 2 Diabetes Mellitus Patients

Background and Objectives: Metformin is a cornerstone in the treatment of type 2 DM (type 2 diabetes mellitus) and is used as 1st line therapy. Studies showed that an average of 10-30% of patients on metformin for longer duration and at higher dosage had Vit. B12 deficiency. Sr.(Serum) Vit. B12 levels were studied and correlated with presence of peripheral neuropathy in type 2 DM patients on long term Metformin, attending OPD of our hospital. Methods: 100 consecutive type 2 DM patients on Metformin for &amp;gt;3 years, aged &amp;gt;18 years attending OPD of the Dept. of Medicine from 1st January - 31st December 2017, were included in our study after the informed consent. Estimation of Sr. Vit. B12 levels was done and correlated with monofilament testing in all the study participants and metformin doses of 1 gm/day and &amp;gt;1 gm/day were classified. Results: In our study, 35% of Diabetic patients on Metformin had Vit. B12 deficiency with mean 168.2 ± 17.9 pg/ml which also correlated with the abnormalities in the monofilament testing, graded on a scale of 1-10, 1 being severe peripheral neuropathy and 10 being normal. The mean monofilament score was found to be 6 out of 10. The remaining 65% had a mean Vit. B12 level of 502.3 ± 16.8 and a mean monofilament score of 8 out of 10. Total mean Vit. B12 level was found to be 619.2. By applying Chi square test as test of significance, odds of positive outcome for monofilament test in Vit. B12 deficient person is 25.5 and p value is significant (P&amp;lt;0.001). Degree of dosage of metformin did not have any significant correlation with Sr. Vit. B12 levels and monofilament score. We also found evidence of Megaloblastic anemia in study participants, with 29% of patients having high MCV with a mean of 98.4 ± 2.1 fl, and dimorphic (23%) and macrocytic (6%) picture on peripheral smear. The mean Hb range was 11.1 to 14.0 g/dL. Conclusion: There is higher prevalence of Vit. B12 deficiency and linear correlation with peripheral neuropathy with long term Metformin use in type 2 DM patients which needs to be diagnosed and treated. Disclosure V. Kothiwale: None. N.D. Chafekar: None. P. Babaliche: None. N.A. Chougule: None.

Metformin use in type 2 diabetic patients is not associated with lower arterial stiffness: the Maastricht Study.

Type 2 diabetes (T2D) is associated with cardiovascular disease complications such as myocardial infarction and stroke. These complications are at least partially the consequence of diabetes-associated increased arterial stiffness. Metformin, a first choice oral glucose-lowering drug, has been associated with potential cardio-protective effects. However, there are no data on the association between real-life metformin use and arterial stiffness. The objective of the current study is to investigate in a population-based sample of individuals with T2D the association between metformin use and aortic stiffness (i.e. carotid-femoral pulse wave velocity, cfPWV) and carotid stiffness [i.e. carotid distensibility coefficient and Young's elastic modulus (YEM)]. We used data from The Maastricht Study, an ongoing observational prospective population-based cohort study (current N = 3451). All participants with T2D, based on pharmacy records (N = 672, 31.3% women, mean age 62.6 ± 7.7), were included in the current study. Linear regression analyses were used to study the association between current metformin use and cfPWV, distensibility coefficient and YEM, as compared with no metformin use. Furthermore, metformin use was stratified by cumulative dose (in grams), continuous duration of use (in days), average daily dose (in grams) and time since first prescription (in years). Regression coefficients of distensibility coefficient were multiplied by -1, consequently, for all arterial stiffness indices, a positive regression coefficient signifies increasing arterial stiffness. Linear regression showed that neither current metformin use was associated with cfPWV [adjusted B: -0.04 (-0.11 to 0.02)] nor metformin use was as stratified by cumulative dose, by continuous duration of use, by average daily dose or by time since first prescription. Metformin use was statistically significantly associated with higher carotid stiffness as assessed by distensibility coefficient [0.12 (0.01 to 0.23)], but not with YEM [0.10 (-0.03 to 0.22)]. However, there was no consistent pattern with the different stratifications of metformin use when further investigating the association with distensibility coefficient. We showed that there is no significant association between current metformin use and aortic stiffness, regardless of how metformin use in itself was defined. In addition, metformin use was not associated with a lower carotid stiffness. The present results showed no beneficial effect of metformin use, dosage or duration on arterial stiffness in middle-aged patients with T2D. Alternatively, metformin may exerts its cardio-protective effects via other pathways.

Metformin and the Risk of Dementia in Type 2 Diabetes Patients.

This retrospective cohort study investigated dementia risk associated with metformin use in type 2 diabetes patients by using the reimbursement database of the Taiwan’s National Health Insurance. The patients had new-onset diabetes during 1999-2005 and were followed up until December 31, 2011. An unmatched cohort of 147,729 ever users and 15,676 never users of metformin were identified, and a matched-pair cohort of 15,676 ever users and 15,676 never users was created by propensity score (PS). Hazard ratios were estimated by Cox regression incorporated with the inverse probability of treatment weighting using PS. Results showed that in the unmatched cohort, 713 never users and 3943 ever users developed dementia with respective incidence of 1029.20 and 570.03 per 100,000 person-years. The overall hazard ratio was 0.550 (95% confidence interval: 0.508-0.596). The hazard ratio for the first (<27.0 months), second (27.0-58.1 months) and third (>58.1 months) tertile of cumulative duration of metformin therapy was 0.975 (0.893-1.066), 0.554 (0.506-0.607) and 0.286 (0.259-0.315), respectively. Analyses in the matched cohort showed an overall hazard ratio of 0.707 (0.632-0.791) and the hazard ratio for the respective tertile was 1.279 (1.100-1.488), 0.704 (0.598-0.829) and 0.387 (0.320-0.468). In conclusion, metformin use is associated with a reduced dementia risk.

Metformin in the management of diabetes during pregnancy and lactation.

This review explores the current place of metformin in the management of gestational diabetes (GDM) and type 2 diabetes during pregnancy and lactation. The rationale and basic pharmacology of metformin usage in pregnancy is discussed along with the evidence from observational and randomized controlled trials in women with GDM or overt diabetes. There seems to be adequate evidence of efficacy and short-term safety of metformin in relation to maternal and neonatal outcomes in GDM, with possible benefits related to lower maternal weight gain and lower risk of neonatal hypoglycemia and macrosomia. Additionally, metformin offers the advantages of oral administration, convenience, less cost and greater acceptability. Metformin may, therefore, be considered in milder forms of GDM where glycemic goals are not attained by lifestyle modification. However, failure rate is likely to be higher in those with an earlier diagnosis of GDM, higher blood glucose, higher body mass index (BMI) or previous history of GDM, and insulin remains the cornerstone of pharmacological treatment in such cases. The use of metformin in type 2 diabetes has been assessed in observational and small randomized trials. Metformin monotherapy in women with overt diabetes is highly unlikely to achieve glycemic targets. Hence, the use should be restricted as adjunct to insulin and may be considered in women with high insulin dose requirements or rapid weight gain. There is clearly a need for more clinical trials to assess the effect of combined insulin plus metformin therapy in pregnancy with type 2 diabetes. Additionally, there is a paucity of data on long-term effects in offspring exposed to metformin in utero. It is imperative to further explore its impact on offspring as metformin has significant transplacental transfer and has the potential to impact the programming of the epigenome. Therefore, caution must be exercised when prescribing metformin in pregnant women. More research is clearly needed before metformin can be considered as standard of care in the management of diabetes during pregnancy.

THE RISK OF COBALAMIN DEFICIENCY SYMPTOMS RELATED TO LONG-TERM METFORMIN USE IN T2DM PATIENTS.

Metformin is the first-line oral antidiabetic agent used in the treatment of diabetes mellitus. One of the adverse reactions of the long term use of metformin is cobalamin malabsorption. Clinical and laboratory findings are important in the diagnosis of cobalamin deficiency. This study aimed to evaluate the risk of cobalamin deficiency symptoms related to long-term use of metformin in type 2 diabetes mellitus patients at Pasar Rebo General Hospital in Jakarta. This quantitative, observational study with retrospective cohort design was conducted in outpatient department Pasar Rebo General Hospital November 2015 until January 2016. 200 subjects were recruited and divided into two groups, patients who had been taking metformin for 1-3 years and patients who had been taking metformin for more than 3 years. Each patient was assessed for the presence of cobalamin deficiency symptoms. Cobalamin deficiency symptoms evaluated were symptoms of neuropathy (measured by DN4 questionnaire) and hematologic abnormalities associated to cobalamin deficiency, i.e. macrocytic erythrocyte, hypersegmented neutrophils, and giant bands. There are significant differences in the proportions of neuropathy symptoms (RR 2.36, 95%, p=0.000) and hematologic abnormalities (RR 1.5, 95%, p=0.007) between the two groups. Long-term use of metformin (≥3 years) may increase the risk of cobalamin deficiency symptoms in type 2 diabetes mellitus patients.

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.

A case risk study of lactic acidosis risk by metformin use in type 2 diabetes mellitus tuberculosis coinfection patients

Metformin (MET) has possibilities to be utilized as an adjunct of tuberculosis (TB) therapy for controlling the growth of Mycobacterium tuberculosis (M. tuberculosis). MET enhances the production of mitochondrial reactive oxygen species and facilitates phagosome–lysosome fusion; those mechanism are important in M. tuberculosis elimination. Moreover, MET-associated lactic acidosis (MALA) needs to be considered and the incidence of MALA in patients with type 2 DM–TB coinfection remains unknown. This result contributes much to our understanding about the clinical effect of MET use in type 2 DM–TB coinfection.For the purpose of understanding the MET effect as an adjuvant therapy in TB therapy and insulin simultaneous therapy, an observational clinical study was done in type 2 DM newly TB coinfection outpatients at Surabaya Paru Hospital. Patients were divided into two groups. First group was MET group, in which the patients were given MET accompanying insulin and TB treatment regimens, the golden standard therapy of DM–TB coinfection. MET therapy was given for at least 2 months. Second group was non-MET group, in which the patients were given insulin and TB treatment regimens. The lactate levels in both groups were measured after 2 months.Among 42 participants, there was no case of lactic acidosis during this study period. Data were normally distributed; thus, we continued analysis of the difference using paired T-test with 95% confidence. There was no difference in lactate levels (p=0.396) after MET therapy compared to non-MET group.In this study involving patients with TB pulmonary diseases, there is neither evidence that MET therapy induced lactic acidosis event nor that it increased lactate blood level. Thus, we concluded that MET use in type 2 DM–TB coinfection did not induce lactic acidosis.