Diabetes mellitus (DM) is a prevalent disease that is the sixth leading cause of death in the Philippines. The fruit juice of Crescentia cujete Linn, or “miracle fruit”, is utilized by locals from Agusan del Sur, Zamboanga del Sur, and Zamboanga Sibugay in the Philippines as an anti-diabetic and antioxidant treatment alternative or additive due to the high costs of their current prescriptions. Phytochemical screening of the fruit extract indicated the presence of alkaloids and reducing sugars with trace amounts of saponins, volatile oil, tannins, and polyphenols. Hypoglycemic and antioxidant assays were utilized to determine the potential activity. Alpha-glucosidase inhibition at 10 ppm of the fruit exhibited low enzyme inhibition activity. Methanol/H2O solvent fraction showed notable antioxidant activity in the 2,2-Diphenyl-1-PicrylHydrazyl (DPPH) assay, averaging 55.69% inhibition. For more comprehensive bioactivity comparison of C. cujete, the half-maximal inhibitory concentration (IC50) of α-glucosidase, and 2,2-diphenyl-1-picrylhydrazyl (DPPH) should be identified and various concentration screening protocols for the assays should be conducted to help identify the effective enzyme inhibitory effects of the sample. Mass Spectral Library included 1-Stearoyl-2-hydroxy-sn-glycero-3-phosphocholine, 15(S)-15-Methyl Prostaglandin E1, and 5,6-Dihydroxy-8Z,11Z,14Z-eicosatrienoic acid.

Diabetes mellitus and obesity are two of the most frequent health conditions in the world, prompting medical researchers to seek novel effective treatments. According to World Health Organization (WHO) regulations and several research studies, diabetes is regarded as a significant and leading health concern worldwide. The search for efficient and safe antidiabetic drugs has led to the study of pyridine derivatives, a family of molecules with a wide range of pharmacological characteristics. Pyridines are important heterocyclic chemicals renowned for their various pharmacological properties. Materials were compiled using the three databases of ScienceDirect, PubMed, and Google Scholar. For this study, only English-language publications have been evaluated based on their titles, abstracts, and full texts using keywords like diabetes, pyridine Derivatives, α- glucosidase inhibitors, and α-amylase inhibitors. Pyridine and its derivatives have received a lot of attention due to their wide range of potential uses in medicinal chemistry and pharmacology. Structural alterations and optimization efforts have resulted in higher effectiveness, selectivity, and safety characteristics. These discoveries highlight the importance of pyridine analogues as a novel class of therapeutic agents for diabetes management. The review highlights the significance of pyridine analogues in the development of antidiabetic treatments, opening new avenues for developing drugs and clinical use. The ongoing advancements in the discovery of pyridine derivatives underscore their potential as prospective agents in diabetic treatments.

Inhibition of respiratory chain complex I (NADH dehydrogenase) is a widely encountered biochemical consequence of drug intoxication and a primary consequence of mtDNA mutations and other mitochondrial defects. In an organ-selective form, it is also deployed as antidiabetic pharmacological treatment. Complex I inhibition evokes a pronounced metabolic reprogramming of uncertain purposefulness, as in several cases, anabolism appears to be fostered in a state of bioenergetic shortage. A hallmark of complex I inhibition is the enhanced biosynthesis of serine, usually accompanied by an induction of folate-converting enzymes. Here, we have revisited the differential transcriptional induction of these metabolic pathways in three published models of selective complex I inhibition: MPP-treated neuronal cells, methionine-restricted rats, and patient fibroblasts harboring an NDUFS2 mutation. We find that in a coupled fashion, serinogenesis and circular folate cycling provide an unrecognized alternative pathway of complete glucose oxidation that is mostly dependent on NADP instead of the canonic NAD cofactor (NADP:NAD ≈ 2:1) and thus evades the shortage of oxidized NAD produced by complex I inhibition. In contrast, serine utilization for anabolic purposes and C1-folate provision for S-adenosyl-methionine production and transsulfuration cannot explain the observed transcriptional patterns, while C1-folate provision for purine biosynthesis did occur in some models, albeit not universally. We conclude that catabolic glucose oxidation to CO2, linked with NADPH production for indirect downstream respiration through fatty acid cycling, is the general purpose of the remarkably strong induction of serinogenesis after complex I inhibition.

Introduction: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have recently gained prominence as both anti-diabetic medications and treatments for obesity in pregnancy. Nevertheless, the safety profile concerning maternal and fetal outcomes remains inadequately investigated. This meta-analysis examines the safety of GLP-1 RA utilization in pregnant women, providing valuable insights into maternal and fetal outcomes. Methods: Per PRISMA guidelines, a comprehensive literature search was performed in PubMed, Google Scholar, and Embase, along with snowballing to identify relevant studies reporting adverse maternal or fetal outcomes in pregnant women who used GLP-1 RA or other anti-diabetic medications either preconceptionally or periconceptionally. Maternal outcomes included hypertensive disorders of pregnancy, gestational diabetes, cesarean delivery, and pregnancy loss. Fetal outcomes included preterm birth, major congenital anomalies, and abnormal birth weight. Binary random-effects models were utilized to estimate pooled odds ratios (OR) and 95% confidence intervals (CI). A p-value <0.05 was considered statistically significant. Results: Four studies with 36,963 pregnancies were analyzed. GLP-1 RA was significantly associated with reduced adverse maternal outcomes (OR: 0.72, 95% CI: 0.66-0.79, p < 0.00001) and preterm birth (OR: 0.66, 95% CI: 0.53 - 0.82, p = 0.0001). However, no increased risk of major congenital anomalies was found compared to other medications (OR: 1.08, 95% CI: 0.86-1.37, p = 0.51) or insulin (OR: 1.00, 95% CI: 0.77-1.28, p = 0.98) (Fig 1). Although there was a noticeable trend toward reduced adverse fetal outcomes, the heterogeneity was significant. This variability is likely due to differences in baseline risk, timing of exposure, and how outcomes were defined in the various studies. Conclusion: GLP-1 RA use during pregnancy is associated with improved maternal outcomes and reduced preterm birth, without increased risk of congenital anomalies. Considering the cardiometabolic interplay between pregnancy complications and future cardiovascular disease, these findings support the necessity for future prospective cardio-obstetric studies aimed at assessing the long-term cardiovascular risks for both mothers and their offspring following GLP-1 RA exposure.

DNA methylation, being a predictor of gene-environment interaction, a dynamic and reversible process, and a target of drugs, may help clinicians to step towards precision medicine. Epigenome-wide association studies have linked methylation changes with type 2 diabetes and glycemic control; among such frequently documented differentially methylated loci include TXNIP (Thioredoxin interacting protein) and ABCG1 (ATP-binding cassette Subfamily G Member 1). However, research evaluating the effects of antidiabetic treatment on DNA methylation is quite meager. The current study aimed to evaluate the pre-and post-treatment methylation status of ABCG1 and TXNIP loci in individuals diagnosed recently with type 2 diabetes (T2Ds). In this quasi-experimental study, individuals recently diagnosed with T2Ds were recruited from 1st March 2022 to 12th June 2023 from diabetes OPDS/clinics. We included the participants (total n=75) as groups that were prescribed Metformin (Met)alone (n=25), Metformin and Dipeptidyl Peptidase- 4 4 inhibitors in combination (Met+DDP4I) (n=25), and Metformin andSodium-Glucose co-Transporter 2 Inhibitors in combination (Met+SGLT2I) (n=25). The methylation status of TXNIP and ABCG1 for all the study groups was evaluated by methylation-specific qPCR. Paired T-test and ANOVA were applied to compare the preand posttreatment methylation status of the study groups. Pearson's correlation test followed by multiple linear regression analysis was performed to analyze the respective correlations and effect of different independent variables on the outcome of the study i.e., post-treatment methylation percentages of ABCG1 and TXNIP. In all groups, post-treatment ABCG1 methylation was found to be significantly decreased, post-treatment TXNIP methylation displayed a significant increase. In a model of linear regression, among various dependent variables, BMI was observed to significantly influence post treatment ABCG1 methylation in all groups, including Met alone(β=0.788, p=0.002), Met+DDP4I, (β= 0.754, p=0.04) and Met+SGLT2I(β= 0.733, p=0.027), while post-treatment TXNIP methylation was significantly affected by reduction in HbA1c levels in all groups, Met alone (β= -0.999, p <0.001), Met+DDP4I (β= -0.850 p <0.001)and Met+SGLT2I (β= -1.007,p <0.001). Metformin alone and its combinations with DDP4I and SGLT2I decrease the methylation of ABCG1, while increasing the methylation of TXNIP in patients with type 2 diabetes. The post-treatment ABCG1 methylation is associated with a decrease in BMI, whereas the post-treatment TXNIP methylation is associated with a decrease in HbA1c levels. Considering the effects of antidiabetic drugs on the methylation status of aforementioned loci involved in the control of glycemic and metabolic parameters; the results of the current study may pave a path for the implementation of precision medicine in type 2 diabetes after further validation by large scale clinical studies.

Introduction: This real-world study examined the demographics, clinical characteristics, and treatment of patients with type 2 diabetes mellitus (T2DM) in routine clinical practice in the UAE. Methods: Data were drawn from the Adelphi Real World Diabetes Disease Specific Programme (DSP)TM, a cross-sectional survey of physicians and their patients with T2DM in the UAE from July to October 2022. Patient data were divided into four stratification factors: physician care, HbA1c level, obesity status, and age, with factors then divided into subgroups. Results: Seventy physicians provided data for 849 patients (mean [SD] age 46.4 [10.6] years, with 31.1% of patients ≤40 years of age; 56.8% male; BMI 28.5 [4.4] kg/m2, with 27.3% of patients having a BMI ≥30 kg/m2). The mean HbA1c was 9.0% [1.1%] at diagnosis, 8.8% [1.1%] at the start of current treatment, and 7.5% [0.9%] at the last follow-up visit. Younger age, lower BMI, and shorter time since diagnosis were associated with a lower most recent HbA1c result (each p&lt;0.0001). Overall, 84.5% of patients did not achieve the HbA1c target set by the physician post-treatment. The mean number of treatments was 1.3, and most patients (73%) only received one line of treatment. It took 3.3 years to switch patients from their previous to current therapy; only 59.7% of patients switched because of inadequate HbA1c reduction. Conclusion: Despite receiving prescribed antidiabetic treatment, a high proportion of patients in our survey did not reach their target HbA1c. High HbA1c was correlated with age, time since diagnosis, and BMI, indicating a need for more efficacious treatment, particularly for older and high-BMI patients. Use of more optimal treatments may improve glycemic control and outcomes in this patient population.

193 Background: Cancer survivors with cardiometabolic risk factors often experience reduced access to evidence-based therapies, including GLP-1 receptor agonists (GLP-1RAs), despite elevated risk of diabetes and cardiovascular disease. In March 2022, a national shortage of semaglutide raised concerns that access disparities—particularly in vulnerable populations—could worsen under constrained supply. We aimed to characterize drop-off across GLP-1RA care steps and assess how cancer status and race modified prescribing disparities before and during the shortage. Methods: We conducted a retrospective cascade-of-care cohort study using the TriNetX research network. Adults (≥18 years) with a cancer diagnosis and a subsequent diagnosis of obesity or type 2 diabetes mellitus (T2DM) were included. Exclusion criteria were GLP-1RA contraindications, ECOG&gt;2 or Karnofsky Performance Scale&lt;40. Two cohorts were defined: those diagnosed with obesity/T2DM in the Pre-Shortage Era (Mar 2019–Aug 2021) and Shortage Era (Mar 2022–Aug 2024). The study design was two-fold: first, a cascade-of-care analysis evaluated progression across six stages (eligibility, clinical engagement, metabolic assessment, antidiabetes treatment initiation, GLP-1RA prescription, and persistent GLP-1RA use [≥180 days]), and second, cox proportional hazards models, adjusted for several clinical and demographic covariates, assessed the impact of both cancer status and race on GLP-1RA prescribing patterns. Results: Among 106,457 pre-shortage and 104,863 shortage-era eligible cancer patients, GLP-1RA prescribing increased from 1.4% to 2.8%, yet disparities widened. Cancer patients were significantly less likely to receive GLP-1RA therapy than matched non-cancer patients in both eras (pre-shortage: aHR 0.57, 95% CI 0.55–0.59; shortage: aHR 0.39, 0.38–0.40). Among all cancer survivors, Black patients had persistently lower prescribing rates vs. White patients (shortage: aHR 0.72, 0.64–0.81), while Asian patients experienced newly emergent disparities during the shortage (aHR 0.65, 0.53–0.79) that were not present prior. Fewer than 1% of cancer patients demonstrated persistent GLP-1RA use. The steepest cascade drop-offs occurred between treatment initiation and GLP-1RA prescription and again at sustained use. Conclusions: Despite overall gains in GLP-1RA prescriptions, the semaglutide shortage exacerbated disparities by both cancer status and race in cancer patients. Cancer survivors, especially Black and Asian patients, were disproportionately under-prescribed during the shortage period. These findings underscore the need for equity-centered allocation strategies and real-time monitoring during drug shortages to prevent the amplification of existing access inequities in high-risk populations.

Insulin resistance is one of the main risk factors for the development of diabetes mellitus. The search for natural ingredient-based drugs for antidiabetic treatment is widely carried out through experimental evidence in the laboratory. An in vitro model has advantages in easily maintaining and replicating. It is an appropriate choice for studying insulin resistance. The critical point in conducting insulin experiments in the early stages is to make the skeletal muscle C2C12 myotube form into insulin-resistant cells. For this reason, suitable types of insulin resistance inducers, effective concentrations, and administered inducer methods need to be discussed. This systematic review provides an overview of types of insulin resistance inducers in the C2C12 in vitro method, the effective concentrations in the molecular study of insulin resistance, and the technique administered by the inducer. Methods: The PubMed and Scopus databases were searched from 2012–2022. Results: Palmitic acid is one of the popular insulin resistance inducers. Concentrations of 0.20-0.75 mM palmitic acid are sufficient to cause insulin resistance. Inducing methods were administered simultaneously or in phases, together with the compound. The difference in the addition of inducers in forming the C2C12 cell model of insulin resistance is related to the research objectives for preventive/protective or curative purposes. The methods were successfully reported in establishing an insulin-resistant C2C12 cell model.

A serious, rapidly growing global health issue is diabetes mellitus (Type 2) caused by insulin deficiency or insulin resistance. This is a chronic condition that demands ongoing care and management. Although a variety of anti-hyperglycaemic medications are available, the need for safer, more effective, and affordable antidiabetic treatments remains crucial due to the undesirable side effects associated with existing options. This review primarily highlights the innovative sodium-glucose co-transporter 2 (SGLT-2) inhibitors and explores their various characteristics. Gliflozins represent an important class of medications used to manage type II diabetes by targeting the SGLT2. By inhibiting SGLT2, they effectively reduce blood glucose levels by preventing the kidneys from reabsorbing glucose. This review offers a comprehensive overview of gliflozins approved by leading regulatory authorities such as the Food and Drug Administration (FDA), European Medicines Agency (EMA), and Pharmaceuticals and Medical Devices Agency (PMDA). It explores the design and development of sodium-glucose co-transporter (SGLT) inhibitors, their mechanisms of action, structure-activity relationships, and additional therapeutic applications.

U-shaped association between triglyceride/HDL ratio and all-cause mortality in obese sepsis patients: A retrospective study based on eICU database.

BackgroundPoor glycemic control in type 2 diabetes mellitus (T2DM) leads to serious complications that negatively impact health-related quality of life (HRQoL). This study aimed to assess glycemic control, HRQoL, and their associated factors in T2DM patients.MethodThis is a cross-sectional study and was conducted from May 1 to July 30, 2024. Systematic random sampling technique was used to recruit the study participants. The average fasting blood glucose (FBG) levels of three consecutive tests during follow-up visits were extracted from patient medical records while the data pertaining HRQoL were collected through interview using EQ-5D five-level (EQ-5D-5L) questionnaire and EQ visual analog scale (EQ VAS). EQ-5D-5L utility scores were determined using disutility values established for Ethiopian context. The FBG level was used to categorize patients by glycemic status (controlled or uncontrolled). Binary logistic regression analysis was performed to outline factors associated with glycemic control. Mann–Whitney U and Kruskal–Wallis tests were used to compare the median utility and VAS scores between subgroups. Furthermore, Tobit regression analysis was performed to determine factors associated with HRQoL.ResultsNearly half (48.7%) of the patients were with uncontrolled glycemic levels (out of the target 4.4−72 mmol/L). In the multivariate logistic regression analysis, age, disease duration, comorbid conditions, diabetes complications, adherence to antidiabetic medications, and herbal medicine use were associated with glycemic control. Pain/discomfort, performing usual activities, and anxiety/depression were HRQoL dimensions in which the majority of participants reported problems; 85.8%, 76.2%, and 74.6% of participants, respectively, reported having problems in the dimensions. The overall median (interquartile range) EQ-5D-5L utility score was 0.86 (0.76–0.93) while EQ VAS score was 75.0 (65.0–80.0). The Tobit regression analysis showed that older age, diabetes duration, comorbid conditions, diabetic complications, and herbal medicine use were significantly negatively associated with HRQoL scores. On the other hand, engagement in physical exercise, controlled glycemic level, and adherence to antidiabetic treatments were found to be positively associated.ConclusionIn conclusion, nearly half of the patients were with uncontrolled glycemic level. The majority of participants reported problems in pain/discomfort, usual activities, and anxiety/depression dimensions of HRQoL. Several factors were correlated with both glycemic control and HRQoL. Adherence to antidiabetic medications was positively associated with both glycemic control and HRQoL. In contrast, older age, longer duration of diabetes, presence of comorbidities, diabetic complications, and use of herbal medicine were all negatively associated with both outcomes. On the other hand, adherence to dietary recommendations was positively associated only with glycemic control, while engagement in physical exercise was positively associated only with HRQoL. Moreover, glycemic control was associated with improved HRQoL. The findings underscore the importance of interventions targeting modifiable factors, such as dietary modifications, physical activity, and adherence support, to improve overall glycemic control and HRQoL.

BackgroundPost-transplant diabetes mellitus (PTDM) significantly compromises patient and graft outcomes. Although multiple antidiabetic agents are available, their comparative efficacy and safety profiles in this population remain uncertain.MethodsA systematic literature search was performed across PubMed, Web of Science, Embase, and Cochrane Library to identify clinical trials comparing antidiabetic therapies in PTDM patients. Risk of bias was assessed, and a network meta-analysis was conducted to estimate relative treatment effects. Treatment ranking probabilities, contribution plots, and funnel plots were used to evaluate hierarchy, study influence, and publication bias, respectively.ResultsTwelve studies—including 10 randomized controlled trials (RCTs) and 2 cohort studies—encompassing 7,372 patients were analyzed. The network meta-analysis evaluated four outcomes: HbA1c, fasting plasma glucose (FPG), systolic blood pressure (SBP), and composite major adverse cardiovascular and kidney events (MACE and MAKE). Compared to placebo, insulin produced the greatest reductions in HbA1c (mean difference [MD] − 0.35, 95% CI − 0.90 to 0.20) and FPG (MD − 9.06 mmol/L, 95% CI − 18.66 to 0.53). DPP-4 inhibitors showed the most pronounced decrease in SBP (MD − 3.57 mmHg, 95% CI − 7.29 to 0.16). SGLT2 inhibitors (SGLT2i) demonstrated the strongest tendency to reduce MACE and MAKE events (MD − 1.95, 95% CI − 4.85 to 0.96). SUCRA plots indicated that insulin and SGLT2i ranked highest in glycemic control and safety profiles. Funnel plot analysis suggested a low risk of publication bias.ConclusionInsulin and SGLT2i represent the most efficacious and safest options among antidiabetic treatments for PTDM, supporting their preferential consideration in post-transplant diabetes management. Further large-scale, head-to-head trials are warranted to strengthen these findings.

Objectives: (1) To assess the prescription patterns of antidiabetic drugs in Type 2 diabetes patients in Rural Central India. (2) To assess compliance with American Diabetes Association guidelines for the management of Type 2 diabetes. (3) To assess the clinical and demographic characteristics, such as age, gender, comorbidities, and lifestyle. (4) To assess glycemic control based on glycated hemoglobin (HbA1c) levels. (5) Determine the most commonly prescribed antidiabetic treatments and drug selection factors. Methods: A retrospective observational study of 120 patients evaluated demographics, lifestyle characteristics, comorbidities, HbA1c, and prescribed antidiabetic treatments, with emphasis on guideline compliance. Results: The majority of participants (70.87%) were aged 41–60 years, with a near-equal gender distribution. While 89.17% adhered to lifestyle modifications, 54.17% were overweight, and 12.50% were obese. Risk factors included smoking (35.83%) and alcohol consumption (14.17%). HbA1c levels indicated that 55% had moderate glycemic control (6.5–8), though 16.67% had levels above 10. Common comorbidities included hypertension (45.00%), dyslipidemia (35.00%), and cardiovascular disease (22.50%). The most frequently prescribed antidiabetic therapy was the fixed-dose combination of glimepiride and metformin (54%), with insulin therapy used in 30% of cases. Adherence to American Diabetes Association guidelines was high (90%), though 10% showed non-adherence due to patient refusal or off-guideline practices. Conclusion: The study underscores the importance of holistic diabetes care, addressing lifestyle, pharmacological, and guideline adherence to improve outcomes.

ObjectiveDiabetes mellitus is a growing public health concern in China, with the rural areas of Guangxi facing rising prevalence, poor glycemic control, and limited healthcare access despite national efforts to improve diabetes management. This study aimed to evaluate the level of glycated hemoglobin (HbA1c) control and identify associated factors among patients with diabetes in the rural areas of Guangxi, China, to inform strategies for improving diabetes management in these regions.MethodsA multistage stratified random sampling method was employed. In the first stage, five cities (Nanning, Guilin, Hechi, Chongzuo, and Yulin) were randomly selected, each representing a geographical region of Guangxi (central, eastern, southern, western, and northern). In the second stage, three counties were randomly selected from each city, yielding a total of 15 counties. One county-level hospital with a general internal medicine department was selected in each county for patient recruitment. Data on demographic characteristics (e.g., sex, age, household income, type of medical insurance, educational level, and disease duration) were collected, and laboratory testing was conducted to measure HbA1c levels. Glycemic control was defined as an HbA1c level< 7%. Multivariate logistic regression was used to identify factors associated with glycemic control.ResultsA total of 2,178 patients with diabetes were included, of whom 1,204 (55.28%) were men and 974 (44.72%) were women. The mean age was 63.25 ± 12.71 years, and the mean duration of diabetes was 7.96 ± 4.07 years. The overall HbA1c control rate was 22.68%. Logistic regression analysis revealed that older age (OR = 1.026, 95% CI: 1.017–1.036), longer disease duration (OR = 1.137, 95% CI: 1.104–1.171), use of oral hypoglycemic agents (OR = 0.485, 95% CI: 0.377–0.624), insulin therapy (OR = 0.425, 95% CI: 0.388–0.534), and higher educational level (e.g., primary school: (OR = 6.507, 95% CI: 3.076–13.767); junior high school: (OR = 5.557, 95% CI: 2.818–10.955); senior high school: (OR = 2.848, 95% CI: 1.485–5.462); college: (OR = 2.479, 95% CI: 1.285–4.782); and bachelor’s degree: (OR = 1.915, 95% CI: 0.943–3.889), and higher annual per capita household income (OR = 0.626, 95% CI: 0.528–0.830) were significantly associated with glycemic control (p< 0.05).ConclusionThe HbA1c control rate among patients with diabetes in rural Guangxi was relatively low (22.68%). Targeted interventions should focus on patients who are older, have a longer disease duration, are not receiving antidiabetic treatment, have lower educational levels, or have lower income levels to improve glycemic management in rural areas.

Diabetes Mellitus is a chronic metabolic disorder caused by impaired insulin secretion and/or insulin resistance. Genetic testing through genomic sequencing is one of the modalities available for diabetes mellitus. Genomic sequencing is the process of analysing DNA obtained from a blood sample (or alternatively from tissue samples). Broadly, genomic sequencing plays two major roles in diabetes mellitus: supporting diagnosis and guiding therapeutic approaches. In its development, genomic sequencing has proven valuable for diagnostic investigation in type 1 diabetes and maturity-onset diabetes of the young (MODY), as well as for assessing the polygenic risk score (PRS) in type 2 diabetes. Establishing a definitive diagnosis allows for the selection of individualised therapy. Several randomised controlled trials have demonstrated that the risk of developing diabetes can be reduced by up to half if detected at an earlier stage. Moreover, genomic sequencing can identify genetic variants that influence responsiveness to antidiabetic treatments. At present, several potential antidiabetic agents targeting novel pathways are under development and in various stages of clinical trials. The application of genomic sequencing thus facilitates the implementation of individualised therapy, ultimately contributing to the realisation of precision medicine.

Potential application of quercetin as an anti-diabetic treatment: From molecular mechanism to delivery system design.

Emerging uncertainty on the anti-aging potential of metformin.

Effect of initial combination therapy vs. step-therapy on adherence and persistence in drug naïve type 2 diabetes patients.

Other than Insulin Antidiabetic Treatment Associates with Better Status of Frailty in Patients with Cirrhosis and Type 2 Diabetes on Waiting List for Liver Transplantation

Background: Type 2 diabetes mellitus (T2DM) is a growing global health burden. Conventional treatments have notable drawbacks, prompting interest in natural compounds due to their multi-targeted actions, safer profiles, lower costs, and traditional use, which supports their efficacy. Objective: The efficacy, safety, and potential for integrated therapy of both synthetic and natural anti-diabetic substances are critically assessed in this review. Methodology: Important natural ingredients, including extracts from Rosmarinus officinalis, Zingiber officinale, Trigonella foenum-graecum, Coptis chinensis, Nigella sativa, Elettaria cardamomum, Cinnamomum verum, and Bellis perennis, are evaluated for their capacity to reduce HbA1c levels, along with their active constituents and mechanisms of action. The effectiveness, mechanisms, and safety profiles of synthetic therapies, including insulin, biguanides, sulfonylureas, thiazolidinediones, DPP-4 inhibitors, GLP-1 receptor agonists, and SGLT-2 inhibitors, are also evaluated in this review. Results: This comparative study highlights the strengths and limitations of natural and synthetic therapies for lowering HbA1c, focusing on safety and cost-effectiveness. It explores the potential of integrative approaches that combine both therapy types to enhance outcomes and minimize side effects through synergistic effects. Personalized treatment strategies are also discussed, emphasizing the importance of tailoring interventions to individual genetic and cultural contexts—for instance, the proven benefits of the Mediterranean diet in managing type 2 diabetes. Conclusion: This comprehensive review highlights the need for further research to enhance anti-diabetic treatments and integrate both synthetic and natural approaches into personalized, long-term treatment plans.