Glucagon-like peptide-1 receptor agonist and new-onset diabetes in overweight/obese individuals with prediabetes: A systematic review and meta-analysis of randomized trials.

BACKGROUND: Glucagon-like peptide-1 receptor agonist (GLP-1RA) is incretin-based therapy that possessed significant glucose lowering and weight loss properties. The present study aims to analyze the efficacy of GLP-1RA in the management of overweight/obese individuals with prediabetes. METHODS: A thorough search was carried out on the Cochrane Library, ClinicalTrials.gov, Scopus, and Medline databases until April 3rd, 2024, using a mix of pertinent keywords. This review incorporates randomized clinical trials (RCTs) concerning the efficacy of GLP-1RA for prediabetes. The primary outcome was regression to normoglycemia and/or progression to type 2 diabetes (T2D). We used random-effect models to examine the odds ratio (OR) and mean difference (MD). RESULTS: A total of eight RCTs were incorporated. The results of our meta-analysis indicated that GLP-1RA therapy was associated with higher odds of regression to normoglycemia (OR 4.80; 95%CI: 3.40-6.77, p < 0.00001, I2 = 67 %) and lower risk of progression into T2D (OR 0.27; 95%CI: 0.18-0.42, p < 0.00001, I2 = 0 %) in overweight/obese individuals with prediabetes. Administration of GLP-1RA was also associated with higher reduction in HbA1c (MD -0.28 %; p < 0.00001), fasting glucose (MD -0.45 mmol/L; p < 0.00001), and BMI (MD -1.71 kg/m2; p < 0.00001) in comparison to placebo. However, the administration of GLP-1RA was associated with higher incidence of total adverse events (TAEs), treatment discontinuation due to AEs, hypoglycemia, and gastrointestinal AEs. CONCLUSIONS: This study indicates that while GLP-1RA is a potent therapeutic agent for prediabetes, its adverse effects are concerning, thereby precluding its recommendation as a prediabetes therapy.

Efficacy and Safety of Bromocriptine-QR as an Adjunctive Therapy on Glycemic Control in Subjects with Uncontrolled Type 2 Diabetes Mellitus: A Systematic Review and Meta-analysis.

Introduction: There has been an increasing awareness of the effects of combining bromocriptine-QR with other medications for diabetes mellitus type 2. This study aimed to assess the efficacy and safety of bromocriptine-QR as an adjunctive therapy for patients with uncontrolled type 2 diabetes mellitus. Methodology: This systematic review is registered at the International Prospective Register of Systematic Reviews (CRD42022360326). Literature search was done via MEDLINE, NCBI, Google Scholar, Science Direct, Europe PMC and Cochrane Library databases. We included randomized controlled trials with participants 18 years old and above with uncontrolled type 2 diabetes mellitus. The primary outcome of interest is the efficacy and safety of bromocriptine-QR as an adjunctive therapy for glycemic control. Case reports, case series, reviews and animal studies were excluded. The risk of bias was reviewed using the Cochrane Risk of Bias tool. Meta-analysis was performed using Review Manager 5.4 and presented as a weighted mean difference and 95% confidence interval for changes from the baseline level. Results: Nine studies were included in the systematic review with a total of 2709 participants. The baseline HbA1c in the bromocriptine-QR group was 7.42% and 7.51% in the control group. The bromocriptine-QR group was favoured, outperforming the control group in terms of reducing hemoglobin A1c(HbA1c), with a statistically significant difference (weighted mean difference -0.6%; 95% CI [-0.83,-0.36]; p<0.00001). The most common side effects were nausea (33.75% vs 6.92%), fatigue (13.11% vs 5.94%), and headache (11.17% vs 6.87%). Conclusion: Administration of bromocriptine-QR at a dose range of 1.6 to 4.8 mg/day as an adjunctive therapy reduced HbA1c and FBG in patients with uncontrolled type 2 diabetes mellitus (T2DM). However, there were also statistically greater odds of the occurrence of adverse events such as nausea, vomiting, and headache compared to controls.

Different doses of imeglimin for management of type 2 diabetes mellitus: a systematic review, meta-analysis, and meta-regression of randomized clinical trials.

BACKGROUND: A new medication for type 2 diabetes mellitus (T2DM) called imeglimin can target all three organs involved in the pathogenesis of DM, namely the liver, skeletal muscles, and pancreas. This research seeks to examine the most efficacious and safe dose of imeglimin for the management of T2DM. RESEARCH DESIGN AND METHODS: Using particular keywords, we searched the CENTRAL, Medline, Scopus, and ClinicalTrials.gov databases for pertinent literature. The results of continuous variables were pooled into the mean difference (MD) and dichotomous variables into odds ratio (OR) along with their 95% confidence intervals (95% CI) using fixed-effect models. RESULTS: Our pooled analysis revealed that imeglimin 1000 mg twice daily [MD -0.90% p < 0.00001] and 1500 mg twice daily [MD -0.84% p = 0.0003] as monotherapy was associated with a higher reduction in the HbA1c compared to placebo. This superiority was still maintained when given as combination therapy. Regrettably, there was an observed escalation in gastrointestinal AEs as the dosage of imeglimin was raised, despite the absence of a corresponding improvement in its efficacy in decreasing HbA1c levels. CONCLUSIONS: Our study suggests that imeglimin 1000 mg twice daily may offer the most optimum therapeutic effects for glycemic control without compromising its safety profiles.

The efficacy of thymosin alpha-1 therapy in moderate to critical COVID-19 patients: a systematic review, meta-analysis, and meta-regression.

BACKGROUND: Effort to search for the optimal COVID-19 treatment has continuously been attempted. Thymosin alpha-1 have immunomodulatory properties which may be beneficial in case of viral infection. This study's goal is to determine whether thymosin alpha-1 is effective in treating people with moderate-to-severe COVID-19. METHODS: We searched for literature in 4 database: Scopus, Europe PMC, Medline, ClinicalTrials.gov, and Cochrane Library until March 25th, 2023. If those articles have data on the efficacy of thymosin alpha-1 therapy on COVID-19, they would be included. Risk ratio (RR) and Mean Difference (MD) along with their 95% confidence intervals were used to pool the results of dichotomous and continuous variables, respectively. RESULTS: Pooled data from 8 studies indicated that moderate to critical Covid-19 patients who were receiving thymosin alpha-1 therapy had significantly lower mortality from COVID-19 (RR 0.59; 95% CI 0.37-0.93, p = 0.02, I2 = 84%), but without any difference in the needs for mechanical ventilation (RR 0.83; 95% CI 0.48-1.44, p = 0.51, I2 = 74%) and hospital length of stay (MD 2.32; 95% CI - 0.93, 5.58, p = 0.16, I2 = 94%) compared to placebo. The benefits of thymosin alpha-1 on the mortality rate were significantly affected only by sample size (p = 0.0000) and sex (p = 0.0117). CONCLUSION: Our study suggests that treatment with thymosin alpha-1 may reduce mortality rate in moderate to critical COVID-19 patients. Randomized clinical trials (RCTs) are still required to verify the findings of our study.

Utility of non-invasive liver fibrosis markers to predict the incidence of chronic kidney disease (CKD): A systematic review, meta-analysis, and meta-regression.

BACKGROUND AND AIMS: Chronic kidney disease (CKD) and non-alcoholic fatty liver disease (NAFLD) share common risk factors and pathogenesis mechanisms. However, the association between the degree of liver fibrosis and the incidence of CKD remains unclear. This study aims to examine the utility of non-invasive fibrosis markers to predict the occurrence of CKD. METHODS: Cochrane Library, Scopus, and Medline were searched up to May 20th, 2023 using combined keywords. Literature that analyzes FIB-4, NFS, and APRI to predict CKD incidence was included in this review. We used random-effect models of odds ratio (OR) with 95% confidence intervals (CI) to express the outcomes in this review. RESULTS: Twenty-one studies were included. Our meta-analysis showed that high FIB-4 was associated with a higher incidence of CKD (OR 2.51; 95%CI: 1.87-3.37, p < 0.00001, I2 = 96%). Further regression analysis revealed that this association was significantly influenced by hypertension (p = 0.0241), NAFLD (p = 0.0029), and body mass index (BMI) (p = 0.0025). Our meta-analysis also showed that high NFS (OR 2.49; 95%CI: 1.89-3.30, p < 0.00001, I2 = 96%) and high APRI (OR 1.40; 95%CI: 1.14-1.72, p = 0.001, I2 = 26%) were associated with a higher incidence of CKD. CONCLUSIONS: This study suggests that these non-invasive liver fibrosis markers can be routinely measured both in NAFLD patients and the general population to enable better risk stratification and early detection of CKD.

Efficacy and safety of tixagevimab-cilgavimab as pre-exposure prophylaxis for COVID-19: A systematic review and meta-analysis.

Some proportions of populations, such as immunocompromised patients and organ transplant recipients might have inadequate immune responses to the vaccine for coronavirus disease 2019 (COVID-19). For these groups of populations, administering monoclonal antibodies might offer some additional protection. This review sought to analyze the effectiveness and safety of tixagevimab-cilgavimab (Evusheld) as pre-exposure prophylaxis against COVID-19. We used specific keywords to comprehensively search for potential studies on PubMed, Scopus, Europe PMC, and ClinicalTrials.gov sources until 3 September 2022. We collected all published articles that analyzed tixagevimab-cilgavimab on the course of COVID-19. Review Manager 5.4 was utilized for statistical analysis. Six studies were included. Our pooled analysis revealed that tixagevimab-cilgavimab prophylaxis may decrease the rate of SARS-CoV-2 infection (OR: 0.24; 95% CI: 0.15-0.40, p < 0.00001, I2  = 75%), lower COVID-19 hospitalization rate (OR: 0.13; 95% CI: 0.07-0.24, p < 0.00001, I2  = 0%), decrease the severity risk (OR: 0.13; 95% CI: 0.07-0.24, p < 0.00001, I2  = 0%), and lower COVID-19 deaths (OR: 0.17; 95% CI: 0.03-0.99, p = 0.05, I2  = 72%). In the included studies, no major adverse events were reported. This study proposes that tixagevimab-cilgavimab was effective and safe for preventing COVID-19. Tixagevimab-cilgavimab may be offered to those who cannot be vaccinated or have inadequate immune response from the COVID-19 vaccine to give additional protection.

Prevalence and Determinants of COVID-19 Vaccine Acceptance in South East Asia: A Systematic Review and Meta-Analysis of 1,166,275 Respondents.

Despite its importance in guiding public health decisions, studies on COVID-19 vaccination acceptance and its determinants in South East Asia (SEA) are lacking. Therefore, this study aims to determine the prevalence of COVID-19 vaccine acceptance and the variables influencing the vaccine's acceptance. This review is registered under PROSPERO CRD42022352198. We included studies that reported vaccination acceptance from all SEA countries, utilising five academic databases (Pubmed, MEDLINE, Cochrane Library, Science Direct, and Google Scholar), three Indonesian databases (the Indonesian Scientific Journal Database, Neliti, and Indonesia One Search), two pre-print databases (MedRxiv and BioRxiv), and two Thailand databases (ThaiJo and Thai-Journal Citation Index). The analysis was conducted using STATA 17.0 with metaprop commands. The prevalence for COVID-19 vaccination acceptance in SEA was 71% (95%CI 69-74; I2 99.87%, PI: 68.6-73.5). Myanmar achieved the highest COVID-19 vaccination acceptance prevalence, with 86% (95%CI 84-89), followed by Vietnam with 82% (95% CI 79-85; I2 99.04%) and Malaysia with 78% (95%CI 72-84; I2 99.88%). None of the ten determinants studied (age, sex, education, previous COVID-19 infections, smoking and marriage status, health insurance, living together, chronic diseases, and healthcare workers) were significantly associated with acceptance. This result will be useful in guiding vaccination uptake in SEA.

Efficacy and safety of tirzepatide as novel treatment for type 2 diabetes: A systematic review and meta-analysis of randomized clinical trials.

BACKGROUND AND AIMS: This study aims to explore the efficacy and safety of tirzepatide for patients with type 2 diabetes (T2D). METHODS: Using specific keywords, we comprehensively go through the potential articles on Europe PMC, Scopus, PubMed, and ClinicalTrials.gov sources until July 12th, 2022. We collected all clinical trials that compare tirzepatide 5, 10, or 15 mg once-weekly with placebo or other glucose lowering agents in adult patients with T2D. RESULTS: Nine clinical trials were included. Our pooled analysis revealed the dose-dependent superiority of tirzepatide in reducing HbA1c, ranging from -1.50% with 5 mg to -1.80% with 15 mg when compared with placebo, -0.61% with 5 mg to -0.95% with 15 mg when compared with GLP-1 receptor agonist, and -0.70% with 5 mg to 1.09% with 15 mg when compared with basal insulin. The dose-dependent superiority of tirzepatide was also seen in the bodyweight reduction effect with all comparators. These superiorities were not accompanied by increased odds of hypoglycemia, but there is an increase in gastrointestinal adverse events incidence. CONCLUSIONS: Tirzepatide has shown superiority in glycemic control and bodyweight reduction with a good safety profile in patients with T2D. Tirzepatide may become a future potential drug in the management of T2D.

COVID-19 vaccination acceptance in Jambi City, Indonesia: A single vaccination center study.

Background: Indonesia has not met its vaccination rate target, falling short of 25% in 2021. This study aims to assess all the contributing factors towards vaccine acceptance, hesitance, and refusal in a single vaccination center in Jambi, Indonesia. Materials and methods: We collected primary data from respondents directly through a structured questionnaire. This was a cross-sectional study with total sampling. We included adults vaccinated for the first dose with CoronaVac in Puskesmas Putri Ayu. The data was collected between March 15th and June 3rd, 2021. Multivariate logistic regression analysis was done to analyse the predictive models. Results: There are 522 respondents included in this study. Nearly half of the respondents are male (52.1%) and mostly in the age category of 36-45 years old (21.1%). A total of 443 respondents (84.9%) are "vaccine acceptance," while the rest constitutes "vaccine hesitance and refusal." Multivariate analysis reveals that respondents who obtain permission from work or school to get vaccinated are more likely to be "vaccine acceptance" with an odds ratio (OR) of 1.76 (95% confidence interval [CI] 1.08-2.91; p-value 0.025), and respondents with ≥ 2 comorbidities are less likely to be "vaccine acceptance" with an OR of 0.09 (95% CI 0.01-0.64; p-value 0.015). Conclusions: There is a high vaccine acceptance in this study. Difficulties in getting a work permit and the presence of ≥ 2 comorbidities decrease the willingness to be vaccinated for COVID-19.

Antecedentes: Indonesia no ha alcanzado su objetivo de tasa de vacunación, por debajo del 25% en 2021. Este estudio tiene como objetivo evaluar todos los factores que contribuyen a la aceptación, la vacilación y el rechazo de la vacuna en un solo centro de vacunación en Jambi, Indonesia. Materiales y métodos: recopilamos datos primarios de los encuestados directamente a través de un cuestionario estructurado. Este fue un estudio transversal con muestreo total. Se incluyeron adultos vacunados para la primera dosis con CoronaVac en Puskesmas Putri Ayu. Los datos se recopilaron entre el 15 de marzo y el 3 de junio de 2021. Se realizó un análisis de regresión logística multivariante para analizar los modelos predictivos. Resultados: Hay 522 encuestados incluidos en este estudio. Casi la mitad de los encuestados son hombres (52,1%) y la mayoría se encuentran en la categoría de edad de 36 a 45 años (21,1%). Un total de 443 encuestados (84,9%) son "aceptación de la vacuna", mientras que el resto constituye "vacilación y rechazo a la vacuna". El análisis multivariado revela que los encuestados que obtienen permiso del trabajo o la escuela para vacunarse tienen más probabilidades de "aceptar la vacuna" con una razón de probabilidad (OR) de 1,76 (intervalo de confianza [IC] del 95%: 1,08-2,91; valour de p 0,025), y los encuestados con ≥ 2 comorbilidades tienen menos probabilidades de "aceptar la vacuna" con un OR de 0,09 (IC del 95%: 0,01-0,64; valour de p 0,015). Conclusiones: Existe una alta aceptación de la vacuna en este estudio. Las dificultades para obtener un permiso de trabajo y la presencia de ≥ 2 comorbilidades disminuyen la disposición a vacunarse contra el COVID-19.

Insulin Therapy and Outcome of Coronavirus Disease 2019 (COVID-19): A Systematic Review, Meta-Analysis, and Meta-Regression.

BACKGROUND: Currently, the relationship between insulin therapy and COVID-19 outcome is not yet established. Our study aims to evaluate the possible association between insulin and the composite poor outcome of COVID-19. METHODS: We systematically searched the PubMed and Europe PMC database using specific keywords related to our aims until December 12th, 2020. All articles published on COVID-19 and insulin were retrieved. Statistical analysis was done using Review Manager 5.4 and Comprehensive Meta-Analysis version 3 software. RESULTS: Our pooled analysis showed that insulin use was associated with composite poor outcomes of COVID-19 [OR 2.06 (95% CI 1.70 - 2.48), p < 0.00001, I2 = 83%, random-effect modelling], and its subgroup which comprised of risk of COVID-19 [OR 1.70 (95% CI 1.40 - 2.08), p < 0.00001, I2 = 34%, random-effect modelling], severe COVID-19 [OR 2.30 (95% CI 1.60 - 3.30), p < 0.00001, I2 = 88%, random-effect modelling], and mortality [OR 2.14 (95% CI 1.47 - 3.10), p < 0.0001, I2 = 85%, random-effect modelling]. Meta-regression showed that the association was influenced by age (p = 0.008), but not by diabetes p = 0.423) and cardiovascular disease (p = 0.086). CONCLUSION: Physicians should be more aware and take extra precautions with diabetes patients who use insulin therapy.

Psychological factors affecting COVID-19 vaccine acceptance in Indonesia.

INTRODUCTION: Increasing the rate of vaccination is crucial in combating the COVID-19 pandemic. However, a survey of 112,888 Indonesians found that only 64.8% Indonesians were willing to be vaccinated, with 7.6% refusing all vaccines and 27.6% are unsure. Several factors were related to this vaccine hesitancy and refusal, such as cognitive reflection, trust in authoritative figures, and personality traits. This study aims to identify psychological determinants and other factors associated with vaccine hesitancy and vaccine refusal. This was a cross-sectional study with data collection done in March 2021 using a questionnaire. We collected demographic data, respondents' stance on vaccination, as well as their psychology measurement. IBM SPSS 26.0 (Statistical Package for the Social Sciences, IBM Corp., Armonk, NY, USA) was used for statistical analysis. RESULTS: The data of 190 respondents were collected for this study. There are 165 respondents (86.8%) who belong to "vaccine acceptance", while 25 are "vaccine hesitance" or "vaccine resistance." Multivariate analysis shows that frequency of COVID-19 tests (p = 0.03), smoking status (p = 0.035), agreeableness trait (p = 0.001), trust in government (p = 0.04) and trust in scientist (p = 0.049) are significantly associated with the two population. CONCLUSION: Several demographic and psychological factors affect the COVID-19 vaccine acceptance. The government and other related parties should consider these factors when adjusting for future policies controlling the COVID-19 pandemic and increasing the vaccination rate.

Colchicine treatment can improve outcomes of coronavirus disease 2019 (COVID-19): A systematic review and meta-analysis.

Currently, there is no widely acceptable and proven effective treatment for coronavirus disease 2019 (COVID-19). Colchicine has been shown to offer a benefit in reducing the inflammation in several inflammatory diseases. This study aims to analyze the efficacy of colchicine administration and outcomes of COVID-19. We systematically searched the PubMed and Europe PMC database using specific keywords related to our aims until January 29, 2021. All articles published on COVID-19 and colchicine treatment were retrieved. The quality of the study was assessed using the Newcastle-Ottawa Scale (NOS) tool for observational studies and Revised Cochrane risk-of-bias tool for randomized trials (RoB 2) for clinical trial studies. Statistical analysis was done using Review Manager 5.4 software. A total of eight studies with 5778 COVID-19 patients were included in this meta-analysis. This meta-analysis showed that the administration of colchicine was associated with improvement of outcomes of COVID-19 [OR 0.43 (95% CI 0.34-0.55), p < 0.00001, I2  = 0%, fixed-effect modelling] and its subgroup which comprised of reduction from severe COVID-19 [OR 0.44 (95% CI 0.31-0.63), p < 0.00001, I2  = 0%, fixed-effect modelling] and reduction of mortality rate from COVID-19 [OR 0.43 (95% CI 0.32-0.58), p < 0.00001, I2  = 0%, fixed-effect modelling]. Our study suggests the routine use of colchicine for treatment modalities of COVID-19 patients. More randomized clinical trial studies are still needed to confirm the results from this study.

The prevalence of uninvestigated dyspepsia and the association of physical exercise with quality of life of uninvestigated dyspepsia patients in Indonesia: An internet-based survey.

BACKGROUND: Epidemiological data on the prevalence of uninvestigated dyspepsia (UD) and its impact on the health-related quality of life (HRQOL) in Indonesian population are still lacking. There is no study investigating the association between exercise and the HRQOL in UD patients. We aimed to investigate the prevalence of UD and its association with physical exercise, and its impact on HRQOL in Indonesian patients with UD. METHODS: This was a population-based, cross-sectional study, conducted using an internet-based questionnaire which was randomly distributed throughout Indonesia using the social media. The questionnaire contained socio-demographic details, exercise levels, Rome III criteria for dyspepsia, and SF-NDI (Short Form-Nepean Dyspepsia Index). The frequency, duration, the intensity of exercise, and the classification of exercise according to ACSM (American College of Sports Medicine) were included in the assessment. The screening for UD was conducted using the Rome III criteria and the SF-NDI score was calculated to assess the HRQOL in patients with UD. RESULTS: A total of 2725 valid responses were collected. The overall prevalence of UD in the study was 49.75%. Multiple logistic regression analysis showed that gender (female) and lack of exercise were independently associated with UD (OR 2.07, 95% CI 1.74-2.47, p < 0.001 and OR 1.72, 95% CI 1.42-2.07, p < 0.001). The median SF-NDI score among 1295 UD subjects in non-exercising and exercising groups was 21.00 and 18.00 (p < 0.001), respectively. CONCLUSION: This study demonstrated the prevalence of UD and the association between exercise and HRQOL among UD patients in Indonesia.

Nightmare and Abnormal Dreams: Rare Side Effects of Metformin?

BACKGROUND: Metformin is widely known as an antidiabetic agent which has significant gastrointestinal side effects, but nightmares and abnormal dreams as its adverse reactions are not well reported. CASE PRESENTATION: Herein we present a case of 56-year-old male patient with no known history of recurrent nightmares and sleep disorder, experiencing nightmare and abnormal dreams directly after consumption of 750 mg extended release metformin. He reported his dream as an unpleasant experience which awakened him at night with negative feelings. The nightmare only lasted for a night, but his dreams every night thereafter seemed abnormal. The dreams were vivid and indescribable. The disappearance and occurrence of abnormal dreams ensued soon after the drug was discontinued and rechallenged. The case was assessed using Naranjo Adverse Drug Reaction (ADR) probability scale and resulted as probable causality. CONCLUSION: Metformin might be the underlying cause of nightmare and abnormal dreams in this patient. More studies are needed to confirm the association and causality of this findings.