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Biomedicines
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Diabetes Mellitus: Pharmacological Innovations and Related Therapeutic Benefits
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Diabetes Mellitus: Pharmacological Innovations and Related Therapeutic Benefits

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Molecular and Translational Medicine".

Deadline for manuscript submissions: closed (31 March 2026) | Viewed by 5092

Editor

Dr. Cristina-Mihaela Lăcătuşu

E-Mail Website
Guest Editor
Unit of Diabetes, Nutrition and Metabolic Diseases, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iași, Romania
Interests: type 2 diabetes; obesity; insulin resistance; metabolic syndrome; cardiovascular risk in metabolic diseases
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Modern medical care for people with diabetes mellitus has some distinctive features. First, despite all preventive measures, we have witnessed an accelerated increase in the prevalence of diabetes worldwide; the most recent global estimates suggest that approximately 537 million people have diabetes and that there were 6.7 million diabetes-related deaths in 2021, with this number projected to increase to 783 million in adults by 2045 and 1.31 billion all-age people by 2050. Secondly, there have been extraordinary advancements in diabetes-targeting therapies in recent years, with multiple new therapeutic classes and novel technologies being developed to modify the clinical outcomes of people with diabetes. These innovations have fundamentally changed clinical guidelines, and the pace of development is so swift that medical thinking today has almost completely changed compared to only fifteen or twenty years ago. The fundamentals of diabetes care currently extend well beyond glucose control to weight control, encompass a multifactorial approach to cardiovascular risk, and promote the use of antihyperglycemic medications that also offer cardiorenal benefits. Together with the ever-present need to empower patients to successfully self-manage their disease, all these approaches will hopefully change the quality of life and disease duration for millions of people worldwide. Therefore, this Special Issue focuses on these significant advancements, starting from the first phases of pharmacological research on diabetes and extending to the various benefits we see developing regarding the clinical outcomes of people with diabetes.

Dr. Cristina-Mihaela Lăcătuşu
Guest Editor

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Keywords

  • therapy of diabetes mellitus
  • pharmacological innovations
  • incretins
  • GLP-1 receptor agonists
  • SGLT-2 inhibitors
  • weight control
  • diabetes-related cardiovascular risk
  • non-glycemic benefits of diabetes drugs
  • diabetes-related technologies
  • diabetes outcomes

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Published Papers (4 papers)

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Research

11 pages, 2915 KB  
Article
siRNA-Mediated Reduction of Apolipoprotein CIII Delays Pancreatic Islet Deterioration and Onset of Type 1 Diabetes in Diabetes-Prone BioBreeding Rats
by Patricia Recio-López, Pere Rehues, Per-Olof Berggren, Lisa Juntti-Berggren and Ismael Valladolid-Acebes
Biomedicines 2026, 14(7), 1481; https://doi.org/10.3390/biomedicines14071481 - 30 Jun 2026
Viewed by 341
Abstract
Background/Objectives: Type 1 diabetes (T1D) is an autoimmune disease characterized by progressive β-cell loss. Apolipoprotein CIII (apoCIII), a lipid metabolism regulator, is elevated in T1D and implicated in β-cell apoptosis. Antisense oligonucleotide–mediated apoCIII reduction delays diabetes onset in diabetes-prone BioBreeding (DPBB) rats. [...] Read more.
Background/Objectives: Type 1 diabetes (T1D) is an autoimmune disease characterized by progressive β-cell loss. Apolipoprotein CIII (apoCIII), a lipid metabolism regulator, is elevated in T1D and implicated in β-cell apoptosis. Antisense oligonucleotide–mediated apoCIII reduction delays diabetes onset in diabetes-prone BioBreeding (DPBB) rats. This study examined whether small-interfering RNA (siRNA) targeting apoCIII during the final prediabetic month preserves islet integrity and delays T1D onset. Methods: Two siRNAs targeting rat apoCIII were evaluated in 30-day-old DPBB rats for efficacy and off-target effects. Hepatic and plasma apoCIII levels were measured, and neighboring apolipoprotein gene expression was assessed. The most specific candidate (apoCIII-siRNA2) was selected. Duration of action was determined after a single injection. To study the effects of apoCIII-lowering treatment in vivo, islets from 25-day-old DPBB rats were transplanted into the anterior chamber of the eye of age-matched DPBB recipients. Rats received weekly intravenous injections of apoCIII-siRNA2 from day 30 until diabetes onset. Islet morphology, vascularization, and phagocyte infiltration were assessed by confocal imaging three and five weeks post-transplantation. Results: Both siRNAs reduced apoCIII, but one showed off-target effects and was excluded. A single injection of apoCIII-siRNA2 suppressed plasma apoCIII for approximately one week and weekly treatment maintained low circulating apoCIII levels. Five weeks after transplantation islet morphology and vascularization were preserved, and there was no increase in phagocyte infiltration. This resulted in a delayed onset of diabetes. Conclusions: siRNA-mediated apoCIII reduction delays pancreatic islet deterioration and T1D onset in DPBB rats, supporting apoCIII as a contributing factor to β-cell vulnerability and thereby a potential therapeutic target. Full article
(This article belongs to the Special Issue Diabetes Mellitus: Pharmacological Innovations and Related Therapeutic Benefits)
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14 pages, 1026 KB  
Article
Circulating GDF15 and HbA1c Response to Add-On Exenatide Therapy in Type 2 Diabetes: A Post Hoc Analysis from a Multicenter Trial
by Qi Wu, Kun Yang, Xinyue Liao, Shiyin Zheng, Xiaoyue Zheng, Haining Wang, Jin Yang and Tianpei Hong
Biomedicines 2026, 14(3), 572; https://doi.org/10.3390/biomedicines14030572 - 3 Mar 2026
Viewed by 641
Abstract
Objectives: To assess the influences of growth differentiation factor 15 (GDF15) on the reduction in glycated hemoglobin (ΔHbA1c) induced by exenatide in type 2 diabetes mellitus (T2DM). Methods: This analysis included 166 participants with T2DM who received exenatide as add-on therapy [...] Read more.
Objectives: To assess the influences of growth differentiation factor 15 (GDF15) on the reduction in glycated hemoglobin (ΔHbA1c) induced by exenatide in type 2 diabetes mellitus (T2DM). Methods: This analysis included 166 participants with T2DM who received exenatide as add-on therapy for 16 weeks. The effect of baseline GDF15 on ΔHbA1c was evaluated using univariate, multivariate, and bidirectional stepwise linear regression models. Baseline GDF15 was categorized into tertiles with the lowest tertile (tertile 1) serving as reference. A subgroup analysis was performed in the participants aged >35 years to investigate whether age influenced the effect of GDF15 on ΔHbA1c. Results: GDF15 levels were significantly increased from baseline following 16 weeks of exenatide treatment [721.9 (513.6, 997.8) pg/mL vs. 741.4 (510.0, 1203.4) pg/mL, p = 0.031]. Univariate linear regression analysis revealed a positive association between baseline GDF15 (tertile 3: β = 0.553, 95% CI 0.115 to 0.991, p = 0.014) and ΔHbA1c. However, no significant relationship was found between GDF15 (tertile 2: p = 0.403; tertile 3: p = 0.217) and ΔHbA1c after adjusting for age and diabetes duration. Further stepwise regression analysis indicated a non-robust association for GDF15 in the absence of age as GDF15 was excluded from the model. Among the participants >35 years old, GDF15 (tertile 3: β = 0.383, 95% CI 0.002 to 0.764, p = 0.049) remained positively associated with ΔHbA1c, even after adjusting for age. Conclusions: Elevated GDF15 might potentially diminish the reduction in HbA1c following 16-week exenatide treatment, with this effect moderated by age. Full article
(This article belongs to the Special Issue Diabetes Mellitus: Pharmacological Innovations and Related Therapeutic Benefits)
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15 pages, 297 KB  
Article
Translating Guidelines into Practice: A Prospective Real-World Study of a Romanian Cohort Treated with GLP-1 RAs
by Mihaela Simona Popoviciu, Delia Reurean-Pintilei, Teodor Salmen, Marius Rus, Anca Ferician, Cristian Sava, Adriana Ioana Ardelean, Lavinia-Alexandra Moroianu and Anca Pantea Stoian
Biomedicines 2025, 13(9), 2174; https://doi.org/10.3390/biomedicines13092174 - 5 Sep 2025
Cited by 1 | Viewed by 1637
Abstract
Background/Objectives: Obesity and type 2 diabetes mellitus (T2DM) have a continuously increasing prevalence and often co-exist, exacerbating cardiometabolic risk. GLP-1 receptor agonists (GLP-1 RAs) are recommended as first-line therapy for patients with T2DM and excess weight, particularly when cardiovascular risk is present. [...] Read more.
Background/Objectives: Obesity and type 2 diabetes mellitus (T2DM) have a continuously increasing prevalence and often co-exist, exacerbating cardiometabolic risk. GLP-1 receptor agonists (GLP-1 RAs) are recommended as first-line therapy for patients with T2DM and excess weight, particularly when cardiovascular risk is present. This study assessed the real-world effectiveness of available GLP-1 RAs in Romania on glycemic control, body weight reduction (BWR), and waist circumference (WC) in T2DM patients with excess weight. Methods: A prospective observational study was conducted on 311 adults with T2DM (glycated hemoglobin (HbA1c) > 7.2%, body mass index (BMI) ≥ 25 kg/m2). Patients received exenatide, semaglutide (either oral or injectable), or dulaglutide and were monitored for a period of 6 months. Parameters assessed included HbA1c, body weight, BMI, and WC. Results: All treatments significantly improved the patients’ HbA1c, BMI, and WC (p < 0.05). Dulaglutide had the most significant impact on HbA1c (−6.69 ± 0.91%), while injectable semaglutide led to the most notable BWR (−4.60 ± 2.74 kg) and WC reduction, especially among male patients. No significant differences in treatment effect were observed concerning the patient’s age, gender, or T2DM duration. Conclusions: In real-world clinical practice, GLP-1 RAs provide significant metabolic benefits and should be considered as part of individualized treatment strategies for T2DM patients who are overweight or obese. Full article
(This article belongs to the Special Issue Diabetes Mellitus: Pharmacological Innovations and Related Therapeutic Benefits)
16 pages, 5798 KB  
Article
Ramulus Mori (Sangzhi) Alkaloids Improve Pancreatic β-Cell Function Through Gut Microbial and Intra-Islet 2-Methoxyestradiol Biosynthesis
by Nan Wu, Lusi Lu, Yiming Liu, Sunyue He, Chunyi Xu, Ying Wu, Yuchen Zhao, Xihua Lin, Wenjing Zhang and Jiaqiang Zhou
Biomedicines 2025, 13(8), 2013; https://doi.org/10.3390/biomedicines13082013 - 19 Aug 2025
Cited by 1 | Viewed by 1716
Abstract
Background: Ramulus Mori (Sangzhi) Alkaloids (SZ-A) are natural hypoglycemic compounds known to enhance insulin secretion. Given the emerging role of the gut microbiota in regulating β-cell function, in this study, we aimed to investigate whether SZ-A exert their beneficial effects through modulating [...] Read more.
Background: Ramulus Mori (Sangzhi) Alkaloids (SZ-A) are natural hypoglycemic compounds known to enhance insulin secretion. Given the emerging role of the gut microbiota in regulating β-cell function, in this study, we aimed to investigate whether SZ-A exert their beneficial effects through modulating the gut microbiota and its metabolites. Methods: A diabetic mouse model was established using a high-fat diet and streptozotocin, followed by 20 weeks of SZ-A treatment. Gut microbiota and metabolites were profiled via 16S rRNA sequencing and liquid chromatography–mass spectrometry, respectively. Spearman’s correlation analysis was used to explore associations between gut microbiota and metabolites. Single-cell RNA sequencing (scRNA-seq) was used to assess gene expression and signaling pathway changes in β cells. Results: Our results demonstrate that SZ-A alleviated hyperglycemia and increased islet numbers in T2DM mice. SZ-A treatment also reshaped the gut microbiota, notably enriching quantities of Lactobacillus and norank_f__Eubacterium_coprostanoligenes_group, which may contribute to increasing levels of 2-methoxyestradiol (2-ME), a bioactive metabolite. Moreover, scRNA-seq revealed an increased proportion of COMT+ cells in the islets, suggesting that 2-ME may also be synthesized within the islets. In vitro, 2-ME suppressed HIF-1α signaling and promoted insulin secretion, indicating that 2-ME may act as a crucial mediator of the beneficial effects of SZ-A. Conclusions: SZ-A improve β-cell function by increasing 2-ME levels via gut microbiota modulation and islet production, ultimately suppressing HIF-1α signaling and restoring β-cell homeostasis. Full article
(This article belongs to the Special Issue Diabetes Mellitus: Pharmacological Innovations and Related Therapeutic Benefits)
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