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Pharmaceuticals
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Emerging Therapies for Diabetes and Obesity
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Emerging Therapies for Diabetes and Obesity

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Pharmacology".

Deadline for manuscript submissions: 15 January 2026 | Viewed by 3216

Special Issue Editor

Dr. Pedro Cisternas

E-Mail Website
Guest Editor
Núcleo de Investigación en Nutrición y Ciencias Alimentarias (NINCAL), Facultad de Salud y Ciencias Sociales, Universidad de las Américas, Santiago, Chile
Interests: Alzheimer's disease; brain metabolism; obesity
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Diabetes and obesity are among the most pressing global health challenges of the 21st century. Their growing prevalence, along with the high burden of associated comorbidities such as cardiovascular disease, non-alcoholic fatty liver disease, and neurodegeneration, demands innovative and effective therapeutic approaches. While current pharmacological treatments provide benefits in glycemic control and weight reduction, long-term efficacy, safety, and patient adherence remain significant concerns.

This Special Issue, “Emerging Therapies for Diabetes and Obesity”, aims to highlight the latest advances in the development of novel therapeutic agents, including small molecules, biologics, phytochemicals, and metabolic modulators. Of particular interest are interventions targeting insulin resistance, adipose tissue dysfunction, beta-cell preservation, gut-brain axis regulation, and inflammation. We also welcome research focused on combination therapies, drug repurposing, and personalized medicine approaches that consider genetic, metabolic, and lifestyle factors.

Submissions may include original research articles, preclinical studies, clinical trials, reviews, and meta-analyses that offer mechanistic insights or translational relevance. Interdisciplinary contributions at the interface of pharmacology, molecular biology, endocrinology, and systems medicine are especially encouraged.

Through this Special Issue, we aim to provide a comprehensive and up-to-date overview of emerging pharmacological strategies for the prevention and treatment of diabetes and obesity, ultimately contributing to the discovery of safer, more effective, and sustainable therapeutic options for patients worldwide.

Dr. Pedro Cisternas
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceuticals is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • insulin resistance
  • adipose tissue dysfunction
  • antidiabetic agents
  • metabolic disease
  • metabolic inflammation
  • pharmacological interventions

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Published Papers (5 papers)

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Research

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19 pages, 7053 KB  
Article
Investigating the Therapeutic Mechanisms of Shen-Ling-Bai-Zhu-San in Type 2 Diabetes and Ulcerative Colitis Comorbidity: A Network Pharmacology and Molecular Simulation Approach
by Qian Yu, Shijie Sun, Tao Han, Haishui Li, Fan Yao, Dongsheng Zong and Zuojing Li
Pharmaceuticals 2025, 18(10), 1516; https://doi.org/10.3390/ph18101516 - 10 Oct 2025
Viewed by 421
Abstract
Objectives: Shen-Ling-Bai-Zhu-San (SLBZS) is a classical traditional Chinese herbal formula with spleen-invigorating and dampness-resolving properties. Recent pharmacological studies suggest its potential to regulate immune and metabolic disorders. Type 2 diabetes mellitus (T2D) and ulcerative colitis (UC) often coexist as comorbidities characterized by [...] Read more.
Objectives: Shen-Ling-Bai-Zhu-San (SLBZS) is a classical traditional Chinese herbal formula with spleen-invigorating and dampness-resolving properties. Recent pharmacological studies suggest its potential to regulate immune and metabolic disorders. Type 2 diabetes mellitus (T2D) and ulcerative colitis (UC) often coexist as comorbidities characterized by chronic inflammation, microbial imbalance, and insulin dysregulation, yet effective therapies remain limited. This study aimed to investigate the molecular mechanisms through which SLBZS may benefit T2D–UC comorbidity. Methods: An integrative multi-omics strategy was applied, combining network pharmacology, structural bioinformatics, and ensemble molecular docking–dynamics simulations. These complementary approaches were used to identify SLBZS bioactive compounds, predict their putative targets, and examine their interactions with disease-related biological networks. Results: The analyses revealed that flavonoids in SLBZS act on the SLC6A14/PI3K–AKT signaling axis, thereby modulating immune responses and improving insulin sensitivity. In addition, SLBZS was predicted to regulate the NF-κB/MAPK signaling pathways, key hubs linking inflammation and metabolic dysfunction in T2D–UC. These dual actions suggest that SLBZS can intervene in both inflammatory and metabolic processes. Conclusions: SLBZS demonstrates promising therapeutic potential for T2D–UC by targeting interconnected immune–metabolic networks. These findings not only provide mechanistic insights bridging traditional therapeutic concepts with modern pharmacology but also establish a theoretical basis for future experimental validation and clinical application. Full article
(This article belongs to the Special Issue Emerging Therapies for Diabetes and Obesity)
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18 pages, 3244 KB  
Article
Effect of Combination Therapy with Probiotic Bulgarian Goat Yoghurt Enriched with Aronia melanocarpa Fruit Juice in Patients with Type 2 Diabetes Mellitus and Complication of Diabetic Nephropathy: A Pilot Study
by Petya Goycheva, Kamelia Petkova-Parlapanska, Ekaterina Georgieva, Nikolina Zheleva, Mariya Lazarova, Yanka Karamalakova and Galina Nikolova
Pharmaceuticals 2025, 18(9), 1409; https://doi.org/10.3390/ph18091409 - 19 Sep 2025
Viewed by 496
Abstract
Background: Goat milk and its fermented products exhibit unique nutritional and therapeutic characteristics corresponding to the management of metabolic disorders, such as type 2 diabetes mellitus (T2DM) and its associated complications, including diabetic nephropathy (DN). Due to its rich content of bioactive [...] Read more.
Background: Goat milk and its fermented products exhibit unique nutritional and therapeutic characteristics corresponding to the management of metabolic disorders, such as type 2 diabetes mellitus (T2DM) and its associated complications, including diabetic nephropathy (DN). Due to its rich content of bioactive compounds and superior digestibility compared to cow’s milk, goat milk enhances nutrient assimilation and exhibits notable anti-inflammatory and antioxidant effects. The primary aim of this investigation was to systematically evaluate the efficacy of goat milk-based nutritional interventions as an integral component of a multifaceted therapeutic approach aimed at attenuating oxidative stress (OS), restoring metabolic homeostasis, and mitigating the progression of long-term complications in patients with diabetes mellitus and concurrent renal dysfunction. Methods: Participants diagnosed with T2DM were stratified into three subgroups based on the severity of renal dysfunction. The results were analyzed in comparison with those of healthy control subjects. Results: Following a dietary regimen that included goat milk enriched with Aronia (Aronia melanocarpa) fruit juice patients—particularly those with DN—exhibited marked reductions in free radical concentrations, decreased cytokine production, and diminished levels of lipid and protein oxidation byproducts. Moreover, a significant improvement was observed in nitric oxide (NO) levels, along with partial restoration of the nitric oxide synthase (NOS) system and an upregulation of endogenous antioxidant enzyme activity (p < 0.05) relative to pre-intervention measurements. Conclusions: These outcomes suggest that the dietary intervention not only attenuated OS but also contributed to improved renal function in affected individuals. The results support the therapeutic potential of functional dairy-based diets—specifically those incorporating bioactive ingredients such as Aronia melanocarpa fruit juice and goat milk—in mitigating oxidative damage and enhancing metabolic and renal health in patients with T2DM and DN. Full article
(This article belongs to the Special Issue Emerging Therapies for Diabetes and Obesity)
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14 pages, 665 KB  
Article
Impact of Adding GLP-1 Receptor Agonists to Insulin Therapy on Cardiovascular and Microvascular Outcomes in Type 2 Diabetes: A Nationwide Cohort Study from Taiwan
by Fu-Shun Yen, James Cheng-Chung Wei, Chen-Yu Sung, Pei-Yun Li, Fuu-Jen Tsai, Chih-Cheng Hsu and Chii-Min Hwu
Pharmaceuticals 2025, 18(9), 1368; https://doi.org/10.3390/ph18091368 - 12 Sep 2025
Viewed by 878
Abstract
Background/Objectives: Selecting appropriate non-insulin hypoglycemic agents to complement insulin therapy is essential for achieving optimal glycemic control. This study aimed to evaluate the impact of glucagon-like peptide-1 receptor agonist (GLP-1 RA) plus insulin therapy on long-term cardiovascular and microvascular outcomes in patients with [...] Read more.
Background/Objectives: Selecting appropriate non-insulin hypoglycemic agents to complement insulin therapy is essential for achieving optimal glycemic control. This study aimed to evaluate the impact of glucagon-like peptide-1 receptor agonist (GLP-1 RA) plus insulin therapy on long-term cardiovascular and microvascular outcomes in patients with type 2 diabetes (T2D), with the goal of optimizing treatment strategies. Methods: Using Taiwan’s National Health Insurance Research Database (2008–2021), we conducted a retrospective cohort study and identified 6779 propensity score-matched pairs of insulin-treated patients with T2D who initiated either GLP-1 RAs or dipeptidyl peptidase-4 (DPP-4) inhibitors. Cox proportional hazard models were applied to compare outcome risks between the two groups. Results: The mean follow-up was 3.45 years. Compared with DPP-4 inhibitor use, GLP-1 RA use was significantly associated with a reduced risk of major adverse cardiovascular events (aHR 0.52, 95% CI 0.46–0.58), including hospitalizations for coronary artery disease (aHR 0.64, 95% CI 0.54–0.75), stroke (aHR 0.48, 95% CI 0.40–0.56), and heart failure (aHR 0.33, 95% CI 0.25–0.42). GLP-1 RA use was also linked to lower risks of major microvascular complications (aHR 0.42, 95% CI 0.35–0.50), end-stage kidney disease (aHR 0.08, 95% CI 0.04–0.14), sight-threatening retinopathy (aHR 0.62, 95% CI 0.50–0.76), leg amputation (aHR 0.16, 95% CI 0.05–0.57), and all-cause mortality (aHR 0.38, 95% CI 0.32–0.44). Conclusions: In this nationwide cohort, adding GLP-1 RAs to insulin therapy in patients with T2D was associated with significantly lower risks of cardiovascular events, major microvascular complications, and all-cause mortality compared with adding DPP-4 inhibitors. These findings suggest that incorporating GLP-1 RAs into insulin regimens may optimize treatment, lessen disease burden, and improve survival. Full article
(This article belongs to the Special Issue Emerging Therapies for Diabetes and Obesity)
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23 pages, 7539 KB  
Article
Effect and Mechanism of Qihua Tongtiao Formula (QHTTF) on Improving Glucose and Lipid Metabolism Disorders in ZDF Rats by Integrating Network Pharmacology, Metabolomics, and Biological Validation
by Yuhua Jiang, Hong Yu, Yajing Pan, Binghan Zhang, Yeteng Jing, Jingjing Lei, Ning Li and Jinsheng Yang
Pharmaceuticals 2025, 18(9), 1347; https://doi.org/10.3390/ph18091347 - 8 Sep 2025
Viewed by 741
Abstract
Background: The dysregulation of both glucose and lipid metabolism is the main clinical features of type 2 diabetes. Qihua Tongtiao Formula (QHTTF) is our team’s current clinical empirical formula, and the related patent has been granted. It is composed of Astragalus membranaceus, [...] Read more.
Background: The dysregulation of both glucose and lipid metabolism is the main clinical features of type 2 diabetes. Qihua Tongtiao Formula (QHTTF) is our team’s current clinical empirical formula, and the related patent has been granted. It is composed of Astragalus membranaceus, Atractylodes macrocephala koidz, Aurantii Fructus Immaturus, Radix Bupleuri, Ligusticum chuanxiong hort, Angelicae sinensis radix, Raphanus sativus, and Polyporus umbellatus. It can alleviate tissue pathological damage in type 2 diabetic rats by improving glycolipid metabolism disorders. Nevertheless, the specific mechanisms of QHTTF in the treatment of type 2 diabetes remain unclear. Purpose: This research aims to explore the fundamental effect and underlying mechanism of the QHTTF formula in ZDF rats via network pharmacology, biological validation, and metabolomics technology. Methods: The chemical compounds of QHTTF were initially identified via UHPLC-MS/MS analysis. Meanwhile, drug targets, genes, related diseases, and differential metabolites of QHTTF in the treatment of T2DM were obtained through network pharmacology, molecular docking, and metabolomics. Then, we conducted animal experiments to further explore the therapeutic molecular mechanism of QHTTF in ZDF rats. Results: A total of 39 main chemical components were recognized through LC-MS/MS technology, and 22 remained after the second screening. Network pharmacology and molecular docking results revealed that 59 intersection targets were involved in the treatment of glycolipid metabolic disorders, and the PPARα, PPARγ, and TNF proteins were identified as crucial targets through PPI network analysis. Additionally, serum metabolomics analysis of ZDF rats showed that QHTTF could regulate linoleic acid metabolism, fructose and mannose metabolism, galactose metabolism, fatty acid biosynthesis, and other related signaling pathways. The results of biological experiments proved that QHTTF effectively lowered blood glucose and lipid levels, alleviated hepatic and pancreatic pathological damage, increased the expression of IRS-1 and GLUT4 in the pancreas, and improved insulin resistance, while inhibiting the inflammatory response and oxidative stress, as well as enhancing the expression of liver PPARα, PPARγ, and AMPK proteins in ZDF rats. Conclusions: In summary, QHTTF exerted a significant effect in improving glycolipid metabolism disorders of ZDF rats, which might show therapeutic effects by relieving insulin resistance, mitigating inflammation and oxidative damage, regulating related glucose, fatty acid, and amino acid metabolism, and increasing the expression of PPARα, PPARγ, and AMPK proteins by combining network analysis, metabolomics, and biological research. Full article
(This article belongs to the Special Issue Emerging Therapies for Diabetes and Obesity)
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Review

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36 pages, 1186 KB  
Review
Adipokines at the Metabolic–Brain Interface: Therapeutic Modulation by Antidiabetic Agents and Natural Compounds in Alzheimer’s Disease
by Paulina Ormazabal, Marianela Bastías-Pérez, Nibaldo C. Inestrosa and Pedro Cisternas
Pharmaceuticals 2025, 18(10), 1527; https://doi.org/10.3390/ph18101527 - 11 Oct 2025
Viewed by 284
Abstract
The parallel global increase in obesity and Alzheimer’s disease (AD) underscores an urgent public health challenge, with converging evidence indicating that metabolic dysfunction strongly contributes to neurodegeneration. Obesity is now recognized not only as a systemic metabolic condition but also as a modifiable [...] Read more.
The parallel global increase in obesity and Alzheimer’s disease (AD) underscores an urgent public health challenge, with converging evidence indicating that metabolic dysfunction strongly contributes to neurodegeneration. Obesity is now recognized not only as a systemic metabolic condition but also as a modifiable risk factor for AD, acting through mechanisms such as chronic low-grade inflammation, insulin resistance, and adipose tissue dysfunction. Among the molecular mediators at this interface, adipokines have emerged as pivotal regulators linking metabolic imbalance to cognitive decline. Adipokines are hormone-like proteins secreted by adipose tissue, including adiponectin, leptin, and resistin, that regulate metabolism, inflammation and can influence brain function. Resistin, frequently elevated in obesity, promotes neuroinflammation, disrupts insulin signaling, and accelerates β-amyloid (Aβ) deposition and tau pathology. Conversely, adiponectin enhances insulin sensitivity, suppresses oxidative stress, and supports mitochondrial and endothelial function, thereby exerting neuroprotective actions. The imbalance between resistin and adiponectin may shift the central nervous system toward a pro-inflammatory and metabolically compromised state that predisposes to neurodegeneration. Beyond their mechanistic relevance, adipokines hold translational promise as biomarkers for early risk stratification and therapeutic monitoring. Importantly, natural compounds, including polyphenols, alkaloids, and terpenoids, have shown the capacity to modulate adipokine signaling, restore metabolic homeostasis, and attenuate AD-related pathology in preclinical models. This positions adipokines not only as pathogenic mediators but also as therapeutic targets at the intersection of diabetes, obesity, and dementia. By integrating mechanistic, clinical, and pharmacological evidence, this review emphasizes adipokine signaling as a novel axis for intervention and highlights natural compound-based strategies as emerging therapeutic approaches in obesity-associated AD. Beyond nutraceuticals, antidiabetic agents also modulate adipokines and AD-relevant pathways. GLP-1 receptor agonists, metformin, and thiazolidinediones tend to increase adiponectin and reduce inflammatory tone, while SGLT2 and DPP-4 inhibitors exert systemic anti-inflammatory and hemodynamic benefits with emerging but still limited cognitive evidence. Together, these drug classes offer mechanistically grounded strategies to target the adipokine–inflammation–metabolism axis in obesity-associated AD. Full article
(This article belongs to the Special Issue Emerging Therapies for Diabetes and Obesity)
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