Initiation Of Metformin Therapy Research Articles

Annals for Educators - 6 October 2020.

Annals for Educators - 6 October 2020.

Annals for Educators - 4 February 2020.

Annals for Educators - 4 February 2020.

Stacked classifiers for individualized prediction of glycemic control following initiation of metformin therapy in type 2 diabetes

ObjectiveMetformin is the preferred first-line medication for management of type 2 diabetes and prediabetes. However, over a third of patients experience primary or secondary therapeutic failure. We developed machine learning models to predict which patients initially prescribed metformin will achieve and maintain control of their blood glucose after one year of therapy. Materials and methodsWe performed a retrospective analysis of administrative claims data for 12,147 commercially-insured adults and Medicare Advantage beneficiaries with prediabetes or diabetes. Several machine learning models were trained using variables available at the time of metformin initiation to predict achievement and maintenance of hemoglobin A1c (HbA1c) < 7.0% after one year of therapy. ResultsAUC performances based on five-fold cross-validation ranged from 0.58 to 0.75. The most influential variables driving the predictions were baseline HbA1c, starting metformin dosage, and presence of diabetes with complications. ConclusionsMachine learning models can effectively predict primary or secondary metformin treatment failure within one year. This information can help identify effective individualized treatment strategies. Most of the implemented models outperformed traditional logistic regression, highlighting the potential for applying machine learning to problems in medicine.

Association of Vitamin B12 and Metformin in Type II Diabetes Patients in Bahrain

Objective: Metformin therapy is the gold standard treatment for type 2 diabetic patients. Long term use of metformin has been associated with vitamin B12 deficiency. We aimed to study the level of vitamin B12 in type 2 diabetic patients on metformin, and to determine other factors affecting the level of vitamin B12. Methodology: Out of 344 patients with type 2 diabetes that were interviewed from January to December 2015; 304 (91.3%) were investigated for vitamin B12 levels deficiency. The patient’s lab results from 2015-2016 were reviewed from the electronic hospital information system, patient data file. Result: Most of the patients, 56.4% had a normal vitamin B12 level. In 91% of the patients the treating physician had already investigated for serum vitamin B12 level. Dyslipidemia and hypertension were significantly more (p=0.009 and 0.022 respectively) in patients with normal vitamin B12 level. Percentage of normal B12 level patients was higher (p=0.001)even in more than 20 years of metformin use; 46.7% of more than 20 years Metformin users had vitamin B12 level within 301-450 pg/mL and 33.3% had more than 450 pg/mL. Conclusion: We recommend routine screening for basal vitamin B12 level for all patients with type 2 diabetes mellitus (T2DM) at the initiation of metformin therapy with subsequent annual follow up of the level.

Perfil clínico de los pacientes con diabetes mellitus tipo 2 tratados con inhibidores del cotransportador sodio-glucosa tipo 2 y experiencia clínica real en España

The main aim of the treatment of type 2 diabetes is overall control of cardiovascular risk factors. Almost 50% of patients with type 2 diabetes do not achieve glycaemic targets, and a much higher percentage do not achieve weight and blood pressure targets, despite the therapeutic arsenal that has appeared in the last decade for the treatment of this disease. In addition, antidiabetic secretatogues and insulin are associated with weight gain and an increased risk of hyperglycaemic episodes. Clinical practice guidelines recommend sodium-glucose cotransporter-2 inhibitors (SGLT2i) as an alternative in the same therapeutic step as the other options after initiation of metformin therapy. The present study reviews the most appropriate patient profile for SGLT2i therapy, based on their safety and efficacy demonstrated in controlled clinical trials. The article discusses which patients are at risk of experiencing the possible secondary effects due to the mechanism of action of this new therapeutic class, in whom SGLT2i should be used with caution. These considerations on the profile of patients suitable for SGLT2i therapy are contrasted with the results obtained in daily clinical practice, both in retrospective studies from other countries and from real-world experiences in Spain. This article presents a selection of studies performed in distinct centres with a minimum follow-up of 6 months and compares their results with those from clinical trials. SGLT2i are used in clinical practice in any therapeutic step and the efficacy results are very similar to those reported by controlled clinical trials, with a slightly higher proportion of genitourinary infections and a low dropout rate. Half the reported patients are diabetics receiving insulin therapy plus a gliflozin, showing the wide uptake of this therapeutic strategy by clinicians. SGLT2i are especially attractive due to their additional effectiveness in weight and blood pressure control and the possibility of using them in association with other antidiabetic agents or in monotherapy in patients at any stage of type 2 diabetes.

Use of metformin earlier in pregnancy predicts supplemental insulin therapy in women with gestational diabetes

The use of metformin in gestational diabetes is safe and effective, yet some women require additional insulin therapy to achieve glycaemic targets. We found a significant association between earlier gestational age at initiation of metformin therapy and the necessity for supplemental insulin in women treated with metformin during pregnancy.

The effect of metformin on TSH levels in euthyroid and hypothyroid newly diagnosed diabetes mellitus type 2 patients.

Metformin is the first-line oral hypoglycemic agent in the treatment of type 2 diabetes mellitus with a number of positive effects. The aim of the study was to determine the effect of metformin on TSH levels in euthyroid and hypothyroid newly diagnosed diabetes mellitus type 2 patients. The study included 255 newly diagnosed diabetes mellitus type 2 drug naive patients, 170 euthyroid patinets, group A, 85 hypothiroid patients, group B, and 80 euthyroid DM type 2 patients on metformin therapy for more than 5 years, group C. Patients in groups A and B began metformin treatment with a dose of 2000 mg/day. We assessed baseline TSH, FT3, FT4 levels and TPOab, in groups A , B and C, and 6 months after initiation of metformin therapy in groups A and B. There were no differences in FT3 and FT4 levels after 6 months of metformin treatment in all groups. TSH level in Group A showed some reduction after 6 months of metformin therapy, not statistically significant. The only statistically significant change in Group A is the change of TSH level after 6 months in TPOAb positive patients. There was statiscically significant decrease in TSH level after 6 months in group B. There were no significant differences of basal TSH, FT3 and FT4 levels in groups A and B compared to group C. The results show that metformin has TSH lowering effect in patients with type 2 DM and hypothyreoidism, but also in euthyroid TPOab positive, levothyroxine naive patients. We have shown that the TSH lowering effect of metformin is not dependent on long term metformin therapy (Tab. 2, Ref. 18).

The lost correlation between leptin and CRP in type 2 diabetes

C reactive protein (CRP) is an inflammatory marker believed to be of value in the early prediction of type 2 diabetes (T2DM). Recent studies have shown a positive correlation between leptin and CRP levels. Here, we aimed to study the correlation between leptin and CRP in patients with T2DM. We also studied the effect of metformin therapy on the CRP-leptin correlation in patients with newly diagnosed diabetes. We performed a follow-up study on three groups of participants defined as 1: patients with newly diagnosed T2DM, 2: patients with long-standing T2DM, and 3: healthy controls. Patients with newly diagnosed diabetes were followed for three months after the initiation of metformin therapy. The homeostatic model assessment of insulin resistance (HOMA-IR) decreased, while leptin levels (15.9±1.6 versus 21.4±2.5, p<0.01) increased after metformin therapy. Leptin levels correlated significantly with CRP in healthy controls (r=0.48; p<0.01); patients with newly diagnosed diabetes before (r=0.35; p<0.05), and after (r=0.55, p<0.001) metformin therapy, while there was no significant correlation between leptin and CRP in patients with long-standing diabetes (r=0.15; p=0.55). After multiple adjustments for potential confounders, leptin was the best predictor of CRP in controls (β coefficient=0.433, p<0.01), and patients with newly diagnosed T2DM who received metformin (β coefficient=0.584, p<0.01). Statin treatment did not have any significant effect on the results. This is the first report demonstrating the restorative role of metformin on the leptin-CRP correlation in patients with newly diagnosed diabetes.

Metformin-Associated Exacerbation of Chronic Pancreatitis: A Possible Adverse Drug-Disease Interaction

Objective: To report a case of metformin-associated exacerbation of chronic pancreatitis and examine this possible drug-disease interaction. Case Summary: A 59-year-old woman with chronic pancreatitis (CP) experienced a severe exacerbation of her characteristic chronic abdominal pain 3 weeks after initiation and titration of metformin therapy; the exacerbation resolved upon discontinuation of metformin. The patient presented to the emergency department experiencing nausea and severe right upper quadrant abdominal pain with radiation to the right flank. Persistent abdominal pain, which had been a primary feature of CP, was previously mild and easily controlled with oral analgesics. Laboratory studies ruled out acute pancreatitis and were significant only for elevated glucose (168 mg/dL). Subsequently, she was given intravenous pain and nausea medications and discharged to home. The pain and nausea shortly returned and continued for 3 more days, at which point she telephoned her gastroenterologist, who advised that she discontinue metformin because of possible adverse reaction. Within a few days of discontinuing metformin, the nausea resolved and abdominal pain gradually returned to baseline level. Discussion: Metformin is not generally known to cause or exacerbate pancreatitis, although cases of acute pancreatitis associated with metformin therapy have been reported in the literature. No cases involving chronic pancreatitis have been reported. Consequently, metformin's prescribing guidelines do not contain precautions or contraindications for patients with chronic pancreatitis. Use of the Naranjo probability scale for assessment of this case revealed that the adverse drug effect was possible, reflecting the symptomatic resolution upon discontinuation while accounting for the lack of causative certainty, previous conclusive case reports, as well as the presence of possible nondrug causes. Conclusions: To our knowledge, this is the first case describing metformin-associated exacerbation of chronic pancreatitis. Although this occurrence may be rare, cautionary consideration, education, and monitoring should accompany initiation of metformin therapy in select patients with chronic pancreatitis.

Interplay of insulin resistance and the reproductive and metabolic changes in women with polycystic ovary syndrome

Background: Polycystic ovary syndrome (PCOS) is a complex reproductive, endocrine-metabolic disorder with insulin resistance (IR) as a common feature. Objective: To clarify whether IR and associated hyperinsulinemia play a key role in the pathophysiological changes in PCOS especially, reproductive and metabolic changes, and the efficacy of metformin therapy in these cases. Patients and Methods: Twenty five PCOS patients received metformin 850 mg twice daily for four months and fifteen healthy controls were included in this study. Body mass index (BMI) evaluation followed by ultrasound examination for measurement of antral follicle count (AFC) in both ovaries, oral glucose tolerance test (OGTT), fasting blood glucose, insulin and glucose / insulin ratio (G/I) were measured in addition to serum total testosterone (T), luteinizing hormone (LH) and insulin like growth factor-1 (IGF-1) estimation for all subjects. These parameters were re-evaluated again 4 months after metformin treatment was initiated in PCOS patients. Results: PCOS patients had significantly increased fasting blood glucose levels (P &lt; 0.05), BMI, T, IGF-1 (P &lt; 0.01), LH, insulin levels and AFC (P &lt; 0.001) but G/I ratio was significantly (P &lt; 0.001) lower in comparison to controls. Significant negative correlations between fasting G/I ratio and each of BMI, T, and AFC respectively were evident. Impaired OGTT at baseline was observed in PCOS patients with significant improvement noted after initiation of metformin therapy. Metformin significantly decreased BMI, serum T, LH, IGF-1 levels and AFC and increased the G/I ratio versus pretreatment values. Conclusion: IR plays a vital pathophysiological role in PCOS patients as manifested by causal relationship between insulin resistance and the reproductive and metabolic changes of PCOS. Metformin potentially improves these changes.

Metformin decreases ovarian volume in lean patients with polycystic ovary syndrome (PCOS)

To assess the effects of metformin treatment for 3 months on ovarian volume and ovarian blood flow with Doppler studies in lean patients with polycystic ovary syndrome. Prospective longitudinal study. This study, conducted between May 2002-June 2003, included 27 lean patients with PCOS, (mean age±S.D: 23.9±4.03 years; body mass index: 24.3±4.1 kg/m2). All patients with oligomenorrhea or amenorrhea who also had at least one of the following evidence of hyperandrogenism; a hirsutism score of more than 7, according to Ferriman and Gallway; and/or an elevated serum testosterone level were diagnosed as PCOS, after all the other causes of hyperandrogenism were excluded. Patients received 850 mg metformin bid for 3 months. Measurements of ovarian volumes and ovarian artery Doppler flow meter using systolic/diastolic ratio (S/D); pulsality and, resistance indices (PI and SI) were performed at baseline and 3 months after initiation of metformin therapy. At the end of study, mean right ovarian volume decreased from 12.8 ± 4.7 to 9.3 ± 2.6 cm3 and left ovarian volume has decreased from 13.3 ± 6.1 to 9.6 ± 3.1 cm3, which were found to be statistically significant (p<0.05). However, Doppler parameters (S/D, RI, PI) of both ovaries before and after the treatment were similar (P>0.05). Insulin plays a central regulatory role in the activity of theca and granulosa cells, by possibly increasing intra ovarian free androgens. There is some controversy about the molecular mechanism of action of metformin. It has been demonstrated a direct inhibition of androgen production by metformin in a human ovarian thecal-like androgen producing tumour cell culture study1. The results of our study, which is also in agreement with Genazzani et al.2, may be an evidence for the efficacy of metformin in modulating the ovarian activity. Therefore, we conclude that metformin, in lean PCOS patients, may cause decrease in the ovarian volume by decreasing intraovarian stromal androgens even in relatively short time such as three months. Since this study was completed in a relatively short term, we might not have observed significant blood flow changes.