BACKGROUND AND OBJECTIVE

Orthodontic brackets predispose dental biofilm accumulation causing caries and gingivitis. Chlorhexidine is an adjunct to mechanical plaque removal, but has side-effects (tooth staining, bacterial resistance) due to long term use. This study tested the efficacy of Photodynamic Therapy, which produces reactive oxygen species, to reduce Streptococcus mutans in dental biofilm on orthodontic brackets.

A 5-day S. mutans biofilm was grown on forty enamel-bracket specimens. Thirty-nine specimens were randomized to three treatment groups: A. Distilled Water; B. 0.12% Chlorhexidine (CHX); C. Photodynamic Therapy (PDT) using Toluidine Blue O (TBO) as a photosensitizer, activated by red LED (630nm). After treatment, one random specimen from each group was viewed under Environmental Scanning Electron Microscopy (ESEM); the other 12 specimens, biofilms were collected, weighed, and cultured onto BHI agar plates to determine the number of CFU/mg. For baseline evaluation, one clean and one untreated specimens were preserved for ESEM.

Based on Tukey HSD test, group A had the most S. mutans (37.0573 CFU/mg) and was significantly different (p < 0.05) from groups B (0.1712 CFU/mg) and C (1.1193 CFU/mg), where both showed less bacteria than group A. The statistical difference between groups B and C was insignificant. ESEM images showed specimen A covered with more abundant and denser S. mutans biofilm than specimens B and C, with almost similar morphology showing sparse, less dense, and disintegrated biofilm with unclear cellular walls and presence of amorphous masses.

Both Photodynamic Therapy and 0.12% Chlorhexidine showed a significant reduction of S. mutans in dental biofilm on orthodontic brackets. However, there is no significant difference between them in reducing S. mutans CFU/mg. Photodynamic therapy could be an alternative adjunctive tool to mechanical removal of plaque adhered to orthodontic brackets.

BACKGROUND AND OBJECTIVES

The in vitro bioequivalence assessment using a dissolution apparatus, as specified by the United States Pharmacopeia (USP), is a critical parameter in the formulation and development of generic pharmaceutical products. This study is crucial for evaluating the interchangeability of generic drugs with their reference innovator counterparts. Post-market surveillance of generic drugs ensures consistent quality after distribution in the market. Metformin hydrochloride, a widely prescribed oral hypoglycemic agent for managing type 2 diabetes, is among the most utilized medications globally.

In the Philippines, there is a growing need to assess the bioequivalence of various generic formulations of metformin HCl f ilm coated tablets to ensure compliance with regulatory requirements. The Philippine Food and Drug Administration (FDA) mandates in vivo or in vitro bioequivalence including, dissolution profile comparison, as a prerequisite for the registration of generic drugs. This study aims to evaluate the quality and in vitro bioequivalence of metformin HCl f ilm-coated tablets available in the Philippine market by comparing their dissolution profiles against the innovator, Glucophage. This research seeks to provide insights into the interchangeability, therapeutic equivalence, and overall quality of these generic formulations, thus contributing to public health and regulatory standards.

Generic metformin HCl film-coated tablets were subjected to quality control tests, including weight variation, thickness and diameter, hardness, friability, and disintegration tests, in accordance with USP guidelines. To assess in vitro bioequivalence, dissolution testing was performed, and the concentration of the dissolved drug was determined using a microplate assay reader to measure absorbance. Dissolution profiles of the generic metformin HCl film-coated tablets were compared to that of the innovator drug, Glucophage to evaluate bioequivalence.

All tested generic metformin HCl film-coated tablets complied with USP specifications for quality control tests, except for the hardness test, where three brands failed to meet the required standards. While for dissolution testing, five out of six generic brands demonstrated acceptable dissolution profiles and were bioequivalent to the innovator drug Glucophage. However, one brand (Brand A) failed to meet the bioequivalence criteria, exhibiting a dissolution profile outside the acceptable limits.

This study demonstrates that most generic metformin HCl film-coated tablets available in the Philippine market meet the United States Pharmacopeia (USP) quality control requirements and exhibit in vitro bioequivalence with the innovator drug. However, the failure of three brands to meet the hardness specifications and the lack of bioequivalence in one brand highlight the need for stringent quality assurance and  regulatory oversight. Ensuring compliance with these standards is critical to maintaining the safety, efficacy, and therapeutic interchangeability of generic drugs. These findings emphasize the importance of continuous post-market surveillance to uphold the quality of generic medications in the market, to safeguard public health.

BACKGROUND AND OBJECTIVE

Orthodontic brackets predispose dental biofilm accumulation causing caries and gingivitis. Chlorhexidine is an adjunct to mechanical plaque removal, but has side-effects (tooth staining, bacterial resistance) due to long term use. This study tested the efficacy of Photodynamic Therapy, which produces reactive oxygen species, to reduce Streptococcus mutans in dental biofilm on orthodontic brackets.

A 5-day S. mutans biofilm was grown on forty enamel-bracket specimens. Thirty-nine specimens were randomized to three treatment groups: A. Distilled Water; B. 0.12% Chlorhexidine (CHX); C. Photodynamic Therapy (PDT) using Toluidine Blue O (TBO) as a photosensitizer, activated by red LED (630nm). After treatment, one random specimen from each group was viewed under Environmental Scanning Electron Microscopy (ESEM); the other 12 specimens, biofilms were collected, weighed, and cultured onto BHI agar plates to determine the number of CFU/mg. For baseline evaluation, one clean and one untreated specimens were preserved for ESEM.

Based on Tukey HSD test, group A had the most S. mutans (37.0573 CFU/mg) and was significantly different (pCONCLUSION

Both Photodynamic Therapy and 0.12% Chlorhexidine showed a significant reduction of S. mutans in dental biofilm on orthodontic brackets. However, there is no significant difference between them in reducing S. mutans CFU/mg. Photodynamic therapy could be an alternative adjunctive tool to mechanical removal of plaque adhered to orthodontic brackets.

Background: Metformin has been studied for its anti-proliferative effects on endometrial cells, and it is hypothesized to have a synergistic effect with progestin therapy in suppressing endometrial cell proliferation. This systematic review and meta-analysis aimed to determine the efficacy of adjunctive metformin in the clinical regression of endometrial hyperplasia and early-stage endometrial carcinoma. Methodology: This meta-analysis followed the Cochrane methodology and adhered to the PRISMA 2020 guidelines. Randomized controlled trials (RCTs) were included if they enrolled reproductive-aged women with endometrial hyperplasia (with and without atypia) and endometrial carcinoma who were treated with progestin and metformin. The primary outcome was the complete response rate at 12-16 weeks, and secondary outcomes included relapse rate, clinical pregnancy rate, and live birth rate. Odds ratios (ORs) and 95% confidence intervals (CIs) were used for dichotomous data. Results: Six RCTs were included. The addition of metformin to progestin therapy may increase the complete response rate of endometrial hyperplasia without atypia (OR 5.12, 95% CI 1.17 to 22.41; n=102) and live birth rates (OR 2.51, 95% CI 1.34 to 4.69; n=188) compared to progestin therapy alone, but the certainty of the evidence is low. Metformin did not have a significant effect on the clinical response of endometrial hyperplasia with atypia and endometrial carcinoma, relapse rates, and clinical pregnancy rates. Conclusion Current evidence is uncertain on the potential benefit of metformin with progestin in endometrial hyperplasia and carcinoma. Future high-quality randomized controlled trials with larger sample sizes and longer follow-up periods are needed to support practice recommendations.
Endometrial Hyperplasia ; Endometrial Neoplasms ; Metformin ; Progesterone

Objective: To determine the efficacy of metformin and insulin in the management of gestational diabetes mellitus (GDM). Methodology: Randomized controlled trials (RCT) were retrieved from the databases. All references cited in the articles were also searched by hand to identify additional publications. Studies included were limited to trials on metformin and insulin in the management of GDM in singleton pregnancies. Four RCTs were analyzed in the study. The risk of bias was assessed using Preferred Reporting Items for Systematic reviews and Meta-Analyses Cochrane Collaboration’s tool (Rob 2). Random effects meta-analysis was carried out to pool the data. All analyses were conducted in Review Manager 5.3.5 (2014). Results: Meta-analysis of four RCT involving 807 participants (405 were treated with metformin and 402 were treated with insulin) shows that there was no significant difference between metformin and insulin in achieving glycemic control as to fasting blood sugar (FBS), postprandial blood glucose (PPBG), and glycosylated hemoglobin, mean difference (MD) −0.43 (95% confidence interval [CI] −2.77–1.91; P = 0.72), MD −2.13 (95% CI −5.16–0.90, P = 0.17), MD −0.09 (95% CI −0.20–0.02, P = 0.10), respectively. For maternal outcomes, there was a statistically significant 69% decreased risk of hypoglycemia in the metformin group (risk ratio [RR] 0.31, 95% CI 0.20–0.49; P < 0.001). There was no difference in terms of risk of preterm birth (RR 1.11, 95% CI 0.75–1.64, P = 0.60); hypertensive disorders (RR 1.06, 95% CI 0.71–1.60, P = 0.77); polyhydramnios (RR 1.04, 95% CI 0.51–2.14, P = 0.91); and risk of cesarean delivery (RR 0.90, 95% CI 0.75–1.08, P = 0.27). For neonatal outcomes, there was statistically significant 34% reduction on the risk of neonatal hypoglycemia (RR 0.66, 95% CI 0.46–0.94; P = 0.02) in the metformin group. There was no statistical difference in terms of mean birthweight (MD − 81.34, 95% CI −181.69–19.02, P = 0.11). Metformin has decreased the risk of newborns weighing more than 4000 g, babies with birthweight >90th percentile by 27% (RR 0.73, 95% CI 0.28–1.90, P = 0.52), and 20% (RR 0.80, 95% CI 0.54–1.18,P = 0.26), respectively, but these were not statistically significant. There was no significant difference in terms of risk of birthweight <10th percentile (RR 1.17, 95% CI 0.60–2.31, P = 0.65); APGAR <7 (RR 1.17, 95% CI 0.65–2.08, P = 0.60), birth trauma (RR 0.77, 95% CI 0.23–2.58, P = 0.67), and jaundice requiring phototherapy RR 1.04, 95% CI 0.66–1.65, P = 0.85). Neonatal intensive care unit admission (RR 0.89, 95% CI 0.64–1.23, P = 0.48), respiratory distress syndrome (RR 0.73, 95% CI 0.36–1.50, P = 0.39), transient tachypnea (RR 0.78, 95% CI 0.27–2.19, P = 0.63), and any congenital anomaly (RR 0.58, 95% CI 0.20–1.67, P = 0.31) were decreased in the metformin group but was not statistically significant. Conclusion There was no significant difference between metformin and insulin in achieving glycemic control as to FBS and PPBG among patients with GDM. There was a statistically significant reduction in the risk of maternal and neonatal hypoglycemia in the use of metformin.
Diabetes, Gestational ; Glycemic Control ; Insulin ; Metformin

Female ; Humans ; Hypoglycemic Agents/therapeutic use* ; Insulin Resistance ; Metformin/therapeutic use* ; Phosphatidate Phosphatase ; Pioglitazone/therapeutic use* ; Polycystic Ovary Syndrome/genetics*

Metformin has robust glucose-lowering effects and multiple benefits beyond hypoglycemic effects. It can also be used in combination with various hypoglycemic drugs and is cost effective. In the absence of the strong indications of glucagon like peptide-1 receptor agonist (GLP-1RA) or sodium glucose cotransporter 2 inhibitor (SGLT2i) for cardiorenal protection, metformin should be used as the first-line pharmacological treatment for newly diagnosed type 2 diabetes and the basic drug for the combined treatment of hypoglycemic drugs. Metformin does not increase the risk of liver and kidney function damage, but patients with renal dysfunction should adjust the dosage of metformin based on estimated glomerular filtration rate (eGFR) levels. Moreover, the correct use of metformin does not increase the risk of lactic acidosis. Because long-term use of metformin is associated with a decrease in vitamin B₁₂ levels, patients with insufficient intake or absorption of vitamin B₁₂ should be regularly monitored and appropriately supplemented with vitamin B₁₂. In view of the new progress made in the basic and clinical research related to metformin, the consensus updating expert group updated the consensus on the basis of the Expert Consensus on the Clinical Application of Metformin (2018 Edition).
Humans ; Consensus ; Diabetes Mellitus, Type 2/complications* ; Hypoglycemic Agents ; Metformin/therapeutic use* ; Sodium-Glucose Transporter 2 Inhibitors/therapeutic use* ; Vitamins/therapeutic use* ; China

OBJECTIVES: Metformin is the basic drug for treating diabetes, and the plateau hypoxic environment is an important factor affecting the pharmacokinetics of metformin, but there have been no reports of metformin pharmacokinetic parameters in patients with diabetes mellitus type 2 (T2DM) in the high-altitude hypoxic environment. This study aims to investigate the effect of the hypoxic environment on the pharmacokinetics and assess the efficacy and safety of metformin administration in patients with Type 2 diabetes mellitus (T2DM). METHODS: A total of 85 patients with T2DM taking metformin tablets in the plateau group (n=32, altitude: 1 500 m) and control group (n=53, altitude: 3 800 m) were enrolled according to the inclusion and exclusion criteria, and 172 blood samples were collected in the plateau group and the control Group. A ultra-performance liquid chromatography/tandem mass spectrometry (UFLC-MS/MS) method was established to determine the blood concentration of metformin, and Phoenix NLME software was used to establish a model of pharmacokinetics of metformin in the Chinese T2DM population. The efficacy and serious adverse effects of metformin were compared between the 2 groups. RESULTS: The population pharmacokinetic modeling results showed that plateau hypoxia and age were the main covariates for model building, and the pharmacokinetic parameters were significantly different between the plateau and control groups (all P<0.05), including distribution volume (V), clearance (CL), elimination rate constant (Ke), half-life(T_1/2), area under the curve (AUC), time to reach maximum concentration (T_max). Compared with the control group, AUC was increased by 23.5%, T_max and T_1/2 were prolonged by 35.8% and 11.7%, respectively, and CL was decreased by 31.9% in the plateau group. The pharmacodynamic results showed that the hypoglycaemic effect of T2DM patients in the plateau group was similar to that in the control group, the concentration of lactic acid was higher in the plateau group than that in the control group, and the risk of lactic acidosis was increased after taking metformin in the plateau population. CONCLUSIONS Metformin metabolism is slowed down in T2DM patients in the hypoxic environment of the plateau; the glucose-lowering effect of the plateau is similar, and the attainment rate is low, the possibility of having serious adverse effects of lactic acidosis is higher in T2DM patients on the plateau than on the control one. It is probably suggested that patients with T2DM on the plateau can achieve glucose lowering effect by extending the interval between medication doses and enhancing medication education to improve patient compliance.
Humans ; Diabetes Mellitus, Type 2/drug therapy* ; Metformin/therapeutic use* ; Acidosis, Lactic ; Tandem Mass Spectrometry ; Hypoxia ; Glucose

Childhood and adolescent obesity has become a global epidemic. The interventions mainly include lifestyle intervention, medication treatment and bariatric surgery. Among them, lifestyle intervention, especially intensive lifestyle intervention with participation of family members, is the first-line treatment for obesity in children and adolescents. Both medication and bariatric surgery are adjuvant treatments for severely obese children and adolescents. Currently, metformin is the most widely used drug for the treatment of obesity in children and adolescents in both China and other countries; orlistat and liraglutide are also the drugs that are safe and often used in other countries; other drugs are not recommended. As a tertiary prevention and treatment strategy for obesity, bariatric surgery should be carried out on the basis of good compliance from both the children and their family members, with the cooperation of multiple disciplines. Sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) are the most common types of procedure performed. Meanwhile, as a new treatment method, intra-gastric balloon procedure needs to be paid more attention to its efficacy and safety.
Adolescent ; Humans ; Child ; Pediatric Obesity/prevention & control* ; Obesity, Morbid/surgery* ; Gastric Bypass/methods* ; Metformin ; Gastrectomy/methods* ; Treatment Outcome ; Retrospective Studies

OBJECTIVE: To explore the association between the use of metformin and the risk of ischemic stroke in patients with type 2 diabetes. METHODS: A prospective cohort study was designed from the Fangshan family cohort in Beijing. According to metformin use at baseline, 2 625 patients with type 2 diabetes in Fangshan, Beijing were divided into metformin group or non-metformin group and the incidence of ischemic stroke between the different groups during follow-up was estimated and compared by Cox proportional hazard regression model. The participants with metformin were first compared with all the parti-cipants who did not use metformin, and then were further compared with those who did not use hypoglycemic agents and those who used other hypoglycemic agents. RESULTS: The patients with type 2 diabetes were with an average age of (59.5±8.7) years, and 41.9% of them were male. The median follow-up time was 4.5 years. A total of 84 patients developed ischemic stroke during follow-up, with a crude incidence of 6.4 (95%CI: 5.0-7.7) per 1 000 person-years. Among all the participants, 1 149 (43.8%) took metformin, 1 476 (56.2%) were metformin non-users, including 593 (22.6%) used other hypoglycemic agents, and 883 (33.6%) did not use any hypoglycemic agents. Compared with metformin non-users, the Hazard ratio (HR) for ischemic stroke in metformin users was 0.58 (95%CI: 0.36-0.93; P = 0.024). Compared with other hypoglycemic agents, HR was 0.48 (95%CI: 0.28-0.84; P < 0.01); Compared with the group without hypoglycemic agents, HR was 0.65 (95%CI: 0.37-1.13; P=0.13). The association between metformin and ischemic stroke was statistically significant in the patients ≥ 60 years old compared with all the metformin non-users and those who used other hypoglycemic agents (HR: 0.48, 95%CI: 0.25-0.92; P < 0.05). Metformin use was associated with a lower incidence of ischemic stroke in the patients with good glycemic control (0.32, 95%CI: 0.13-0.77; P < 0.05). In the patients with poor glycemic control, and the association was not statistically significant (HR: 0.97, 95%CI: 0.53-1.79; P>0.05). There was an interaction between glycemic control and metformin use on incidence of ischemic stroke (P_interaction < 0.05). The results of the sensitivity analysis were consistent with the results in the main analysis. CONCLUSION Among patients with type 2 diabetic in rural areas of northern China, metformin use was associated with lower incidence of ischemic stroke, especially in patients older than 60 years. There was an interaction between glycemic control and metformin use in the incidence of ischemic stroke.
Humans ; Male ; Middle Aged ; Aged ; Female ; Metformin/adverse effects* ; Diabetes Mellitus, Type 2/drug therapy* ; Cohort Studies ; Ischemic Stroke/complications* ; Prospective Studies ; Hypoglycemic Agents/adverse effects* ; Stroke/prevention & control* ; Retrospective Studies