Current Drug Therapy - Volume 20, Issue 7, 2025

Type 2 Diabetes (T2D) is a chronic metabolic disease characterized by hyperglycemia and carries a high risk of numerous complications. The rising prevalence of this lifelong condition affects millions globally, demanding novel therapeutic strategies. Existing medications targeting insulin and other pathways often pose limitations like suboptimal glycemic control, side effects, and high costs. Novel therapeutic targets are crucial for developing better treatments and potentially reducing side effects associated with previous drugs.

This paper aims to comprehensively review and analyze potential targets for the treatment of diabetes mellitus.

We conducted a comprehensive search of MEDLINE, Scopus, Science Direct, PubMed, and Google Scholar databases. Search terms included “diabetes mellitus”, “novel targets”, “drug discovery”, “gene expression” and “molecular pathways”. We identified over 175 published articles exploring novel therapeutic targets for DM.

The review presented a detailed analysis of promising anti-diabetic targets. These targets encompass various pathways and mechanisms, including insulin signaling, Glucose signaling, inflammation and oxidative stress, gut microbiome, and epigenetic modifications. Several promising candidates emerged, such as Glucokinase activators, GPCRs modifiers, Fructose-1,6-bisphosphatase antagonists, Protein tyrosine phosphatase 1B antagonist, 11β-Hydroxysteroid, andDehydrogenase antagonists. Potential therapeutic agents targeting these emerging targets will be discussed, along with their mechanisms of action and preclinical/clinical evidence.

By identifying and comprehensively analyzing new therapeutic targets, this review intends to provide insights for the development of more effective and efficient diabetes management strategies. The information presented can guide future research initiatives and drug development efforts toward novel and promising anti-diabetic therapies.

Type 2 Diabetes Mellitus (T2DM) is a prevalent metabolic disorder characterized by insulin resistance and hyperglycemia. Herbal remedies have been explored as alternative or adjunctive therapies for managing T2DM due to their perceived safety and potential antidiabetic properties.

This study aimed to provide a comprehensive examination of the current state of knowledge regarding herbal remedies for managing Type 2 Diabetes Mellitus (T2DM). It explored bioactive compounds in herbs implicated in glycemic control and evaluated their potential therapeutic effects on T2DM from both traditional and contemporary perspectives.

The primary objectives of this in-depth study included scrutinizing the literature on herbal interventions for T2DM, identifying and evaluating the bioactive compounds in herbs implicated in glycemic control, assessing the mechanisms of action responsible for their antidiabetic properties, and investigating the safety profile and potential side effects associated with their use.

A systematic literature search was conducted across multiple databases, including PubMed, Scopus, and Web of Science. Articles published up to the present date, including peer-reviewed research articles, clinical trials, and systematic reviews, were considered for inclusion in this review.

The review presented a thorough analysis of herbal remedies commonly associated with T2DM management. Reductions in HbA1c levels and fasting blood glucose concentrations indicated that the investigated herbal medicines, including fenugreek, cinnamon, and bitter melon, have shown potential results in improving glycemic control in people with type 2 diabetes but more study is needed to verify their safety & effectiveness. The safety profile and possible adverse effects of herbal interventions are also addressed. While some herbs show promise in glycemic control, caution is advised in their use due to the limited number of high-quality clinical trials. The findings highlight the need for further research to validate the efficacy and safety of herbal remedies for T2DM.

The study provided valuable insights into the current understanding of herbal interventions for T2DM and underscored the importance of continued research in this field for the development of evidence-based therapeutic approaches.

Ischemic heart disease and coronary artery disease are both considered to be the causative factors for Acute Coronary Syndrome (ACS). Cardiovascular disease is the primary cause of death and illness in individuals with both type 1 and type 2 diabetes. It has been reported that long-term hyperglycemia causes chronic heart disease.

This study aimed to explore the hyperlinks between dysglycemia and acute coronary syndrome.

Databases specifically designed for medical research, such as PubMed, Medline, Embase, and Google Scholar, were utilized for the study. In addition, data from credible health groups and government authorities were also obtained.

It has been reported that long-term hyperglycemia causes chronic heart disease. Individuals with type 1 diabetes mellitus tend to develop Coronary Heart Disease (CHD), especially if they have nephropathy. The correlation between dysglycemia and ACS is intricate, and individual reactions may differ. The relationship between genes and environment is now recognized to be mediated by epigenetic factors through many sorts of responses, which can help explain the link between diabetes and cardiovascular disease. HbA1c, a measure of long-term glycemic management, may independently increase CHD risk; however, this is unclear.

Poor glycemic management, oxidative stress, insulin resistance indicators, and low-grade inflammation may cause cardiovascular disease and diabetes. Optimal management of blood glucose levels and comprehensive cardiovascular care are essential in minimizing the impact of dysglycemia on Acute Coronary Syndrome (ACS) outcomes.

Those who suffer from migraines, a neurological illness characterized by unilateral pulsating headaches, may find their daily activities impaired. Migraine sufferers often experience non-selective symptoms after taking an oral administration, such as discomfort, nausea, vomiting, and in rare circumstances, auras. The elastic nanovesicles work well as drug-delivery vehicles across the nasal passages and into the brain. Despite kynurenic acid's (KNA) potential as a neuroprotective drug, because of its poor capacity to penetrate the BBB, it has very limited use in therapeutic settings. This is why different drug delivery strategies to deliver KNA to the brain are being explored. This research intended to optimize KNA’s solubility, bioavailability, and penetration across the nasal mucosa for intranasal administration by formulating and evaluating KNA-loaded spanlastics (KNA-SPLs).

Due to its enormous surface area, permeable endothelium membrane, abundant blood flow, ability to avoid first-pass metabolism, and convenience, the nasal mucosa is a promising target for drug delivery. making it an ideal site for drug absorption. The purpose of this investigation was to create KNA-SPLs and KNA spanlastic gel with this information in mind.

After creating the KNA-SPLs with thin-film hydration, a Box-Behnken design (BBD) was used for optimization. The PDI, zeta potential, vesicle size, entrapment efficiency, and in vitro drug release of the KNA-SPLs optimized formulation were evaluated. In addition to pharmacodynamics, confocal scanning laser microscopy (CLSM), and transmission electron microscopy (TEM), researchers looked into the nasal cavity and the brain. KNA-SPLs were prepared as a part of the Carbopol 934P and HPMC K4M liquid gelling system for in situ gelation. The gelling duration, gelling capacity, and viscosity of the resulting solution were evaluated over two pH ranges (5 and 6).

The vesicles' average diameters varied from 102.46 ± 7.68 to 254.31 ± 5.03 nm. The best nano-spanlastic formulation (F3) showed excellent EE% (61.27 ± 0.51%), PDI (0.156 ± 0.01), zeta potential (-29.43 ± 0.38), and drug release > 80%. The ingredients were as follows: phospholipon 90G 70mg, span 60 mg, and tween 80 mg and 75 mg. For sustained release and in vivo bio-distribution, the gelling time (3.240.28) and dissolution rate (> 50% within 24 min) of the produced nasal gel (G5) containing 1% Carbopol and 4% HPMC were much lower. Studies on animals have shown that intranasal treatment significantly increases the pace and extent of brain and plasma absorption, showing a high efficiency for targeting the brain. Pharmacodynamic studies involving Swiss albino mice have corroborated that the treatment formulation crossed the blood-brain barrier, adding credence to the drug's much improved anti-migraine capacity.

When compared to the conventional gel formulations, intranasal administration of KNA has been shown to be feasible with the use of spanlastics. The use of intranasal drug administration to deliver KNA has been reported to be mostly successful. This study demonstrates the efficacy of KNA-SPLs in treating migraine by targeting the brain.