Metformin: New Preparations and Nonglycemic Benefits.

Metformin has been widely used for over 5 decades. New preparations have been developed for possible enhancement of efficiency, tolerability, and pleiotropic nonglycemic effects. Extended-release metformin has contributed to adherence and improved gastrointestinal tolerability. Delayed-release metformin acts in the lower gastrointestinal tract and exerts glucose-lowering effects at lower plasma metformin levels, which might suggest use of this biguanide in patients with chronic kidney disease. Metformin is also known to have numerous nonglycemic effects. Results of the UK Prospective Diabetes Study indicate improvements in cardiovascular outcome and reduced total mortality independent of glycemic control. Anticancer effects of metformin have been discussed and many clinical trials are on-going. Metformin is noted for its beneficial effects on lifespan extension and on disorders due to increased insulin resistance. Further investigations, including randomized control trials in nondiabetic individuals, are required to demonstrate the nonglycemic effects of metformin.

Insights Into Metformin XR Pharmacotherapy Knowledge Among Community Pharmacists: A Cross-Sectional Study.

Background: There is a little knowledge on the extent to which healthcare providers understand and accept the professional recommendations and appropriate dosing strategy regarding metformin XR. Objectives: To evaluate UAE community pharmacists' knowledge, attitude, and practices (KAP) concerning metformin XR. Methods: This is a cross-sectional research study conducted amongst licensed community pharmacists. The survey took place via a questionnaire and physical interviews were held. The survey used in this study included questions on demographics and questions on the participants' attitudes, knowledge and practices concerning metformin XR. The factors influencing KAP regarding metformin XR were examined via simple logistic regression analysis. Results: Threehundred fifty-three (n = 353) participants were recruited in the study. Independent pharmacies constituted 57.5% of this study sample and 42.5% were chain pharmacies. The average knowledge score about metformin XR tablets was 42.5% with a confidence interval (CI) of 95% [37.3%, 47.4]. Better knowledge scores on metformin XR tablets was observed in respondents aged ⩾40 years (OR 2.97, 95% CI 1.63-5.4), having greater than 10 years in terms of experience (OR 2.28; 95% CI 1.25-4.16) and pharmacist graduated from Regional or international universities (OR 2.08; 95% CI 1.34-3.24). About 78% (n = 275) of the participants believed that metformin XR tablets have better efficacy and 63.2% (n = 233) indicated that metformin IR was associated with greater adverse effects. Conclusion: This study demonstrated a distinct gap in knowledge, attitude and practice pertaining to metformin XR among community pharmacists in the UAE. The community pharmacists need to enhance their practice by receiving accurate and reliable data to support their decision-making on the prescribing of metformin XR. The implementation of novel guidelines and evidence dissemination strategies may help bridge this gap.

Feasibility trial of metformin XR in people with pre-diabetes and stroke (MIPPS)-randomised open blinded endpoint controlled trial.

AIMS: Pre-diabetes is a common condition that affects about 16.4% of Australian adults. Hyperglycaemia is a strong risk factor for the development of stroke. Metformin XR is an approved medication to treat type 2 diabetes in Australia but not pre-diabetes. Additionally, whether it is tolerated following a stroke is unclear. In this pilot study, we aimed to assess the feasibility of Metformin XR in people with stroke and pre-diabetes. METHODS: In this PROBE design trial, people who had recent stroke (within 3 months) with pre-diabetes were randomized to either the active arm (n = 13) receiving usual care plus Metformin XR (500 mg daily increased to a total daily dose of 1500 mg) or the control group receiving only usual care (n = 13). At baseline & after four months of intervention, clinical and biomedical characteristics, cardiovascular risk factors and medication data were recorded. At one month and 2.5 months into the study, compliance rateandside effects were determined. RESULTS: This trial showed that it is feasible to recruit, retain and monitor participants. However, the compliance rate was low. Adherence to metformin XR was 52% (IQR:42% to 61%) based on the remaining tablets in the container after 4 months of intervention. None of the reported side effects were deemed to be related to the study treatment and no significant differences were observed between the metformin XR and the control group. CONCLUSION: Treatment with Metformin XR in participants admitted with stroke and with pre-diabetes is feasible and safe. Strategies are needed to improve adherence in future trials.

Knowledge, Attitude, and Practice of Metformin Extended-Release Tablets Among Clinicians in China: A Cross-Sectional Survey.

Background: Metformin extended-release (XR) is a once-daily alternative conventional immediate-release (IR) tablet for adults with type 2 diabetes. Aim: This study aimed to investigate the knowledge, attitude, and practice of the use of metformin XR tablets among clinicians. Methods: We conducted a cross-sectional online survey among endocrinologists, general practitioners, and internists, who are taking routine care of adults with type 2 diabetes in health institutes at all levels in Sichuan Province, China. We designed an online questionnaire including the demographic information, knowledge, attitude, and practice about metformin XR tablets. Results: We included 158 clinicians, 67.7% of whom were females and 63.9% were from tertiary hospitals. The median age was 39.6 years (ranging between 22 and 62 years). Only 8.2% of the clinicians correctly answered the knowledge questions, 82.3% and 62.0% of the responders assumed that metformin XR had superior efficacy and tolerability to the metformin IR, respectively. Only 46.8% of the clinicians prescribed the metformin XR based on the patient's preference for once daily frequency. Conclusion: The knowledge, attitude, and practice of metformin XR among Chinese clinicians need improving. Clinicians need credible information to support their clinical decision-making regarding metformin XR.

Pharmacokinetics of the evogliptin/metformin extended-release (5/1,000 mg) fixed-dose combination formulation compared to the corresponding loose combination, and food effect in healthy subjects.

A new fixed-dose combination formulation of evogliptin 5 mg and metformin extended-release (XR) 1,000 mg (FDC_EVO5/MET1000) was developed to improve medication adherence for type 2 diabetes mellitus. The pharmacokinetics of FDC_EVO5/MET1000 was compared to the corresponding loose combination in a randomized, open-label, crossover study in 36 healthy male subjects (Part 1), and the food effect on FDC_EVO5/MET1000 was assessed (under fasted or fed conditions) in a randomized, open-label, crossover study in 28 healthy male subjects (Part 2). Serial blood samples for pharmacokinetic analysis were collected up to 72 hours, and pharmacokinetic parameters of evogliptin and metformin were calculated using non-compartmental methods. The geometric mean ratios (fixed-dose combination to loose combination) and 90% confidence intervals of pharmacokinetic parameters for evogliptin and metformin were all within 0.800-1.250, suggesting bioequivalent pharmacokinetic. After a single oral dose of FDC_EVO5/MET1000, food did not significantly affect evogliptin pharmacokinetic while systemic exposure of metformin was increased about 47.5% under the fed condition, which is consistent with the already established food effect on metformin XR. FDC_EVO5/MET1000 was generally well tolerated without any drug-related serious adverse events. In conclusion, FDC_EVO5/MET1000 can be substituted for the loose combination of FDC_EVO5/MET1000, providing better compliance with convenient administration.

Bioequivalence, Food Effect, and Steady-State Assessment of Dapagliflozin/Metformin Extended-release Fixed-dose Combination Tablets Relative to Single-component Dapagliflozin and Metformin Extended-release Tablets in Healthy Subjects.

PURPOSE: Simplification of therapeutic regimens for patients with type 2 diabetes mellitus can provide convenience that leads to improved compliance. Dapagliflozin/metformin extended-release (XR) fixed-dose combination (FDC) tablets offer the convenience of once-daily dosing. Two pharmacokinetic (PK) studies were conducted to establish bioequivalence for 2 doses of dapagliflozin/metformin XR FDC versus the same dosage of the individual component (IC) tablets in healthy adults. METHODS: Two open-label, randomized, 4-period, 4-arm crossover studies were conducted to assess the bioequivalence and PK properties of dapagliflozin and metformin FDCs in healthy subjects under fed and fasting conditions. Participants received single oral doses or once-daily dosing of dapagliflozin/metformin XR (5 mg/500 mg [study 1] or 10 mg/1000 mg [study 2]) for 4 days in an FDC formulation or corresponding strengths of IC tablets. FINDINGS: For both of the studies, dapagliflozin and metformin 5 mg/500 mg or 10 mg/1000 mg FDC tablets were bioequivalent to the respective IC tablets. The 90% CIs of the ratio of the adjusted geometric means for all key PK parameters (Cmax, AUC0-T, and AUC0-∞) were contained within the predefined 0.80 to 1.25 range to conclude bioequivalence for both dapagliflozin and metformin. Once-daily dosing to steady state of each FDC tablet had no effect on the PK properties of dapagliflozin or metformin. When the FDCs were administered with a light-fat meal, there was no effect on metformin PK values and only a modest, nonclinically meaningful effect on dapagliflozin PK values. There were no safety or tolerability concerns. IMPLICATIONS: Bioequivalence of the FDCs of dapagliflozin/metformin XR and the ICs was established, and no safety issues of clinical concern were raised.