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Advancements in Cardiovascular and Antidiabetic Drug Therapy, 2nd Edition

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

Deadline for manuscript submissions: closed (31 July 2025) | Viewed by 4259

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Dr. Alfredo Caturano

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Department of Human Sciences and Promotion of the Quality of Life, San Raffaele Roma Open University, 00166 Rome, Italy
Interests: diabetes; diabetes complications; cardiovascular disease; MASLD; Brugada syndrome; arrhythmias
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Dear Colleagues,

Cardiovascular diseases (CVDs) persist as the leading cause of global mortality, claiming 17.9 million lives in 2019, constituting 32% of all global deaths. A staggering 85% of these fatalities were attributed to heart attacks and strokes. Notably, the prevalence of diabetes significantly contributes to these statistics, affecting an estimated 422 million individuals worldwide, with 1.5 million deaths directly linked to diabetes annually.

As vigilant witnesses to the ongoing innovations in cardiovascular care, we have observed significant progress, especially in the realm of drug therapy. The introduction of sodium–glucose cotransporter 2 inhibitors has emerged as a transformative approach for addressing both heart failure and diabetes. Additionally, novel lipid-lowering agents, such as PCSK9 inhibitors and obeticholic acid, have revolutionized cardiovascular prevention. These pharmacological breakthroughs, among others, underscore the dynamic evolution of cardiovascular drug therapy.

In recognition of the pivotal role of drug therapy in shaping the future of cardiovascular and antidiabetic treatments, the journal Pharmaceuticals is thrilled to announce the launch of a Special Issue titled “Advancements in Cardiovascular and Antidiabetic Drug Therapy”. This initiative aims to assemble accurate and current scientific insights focused on drug-based approaches for CVDs and diabetic diseases. I am honored to extend a personal invitation to you and your esteemed co-workers to contribute to this Special Issue by submitting original research articles, systematic reviews and review articles that delve into new ideas and recent advances in the realm of cardiovascular and antidiabetic drug therapy.

Your valuable contributions will undoubtedly shape the trajectory of drug-based interventions, advancing our understanding and capabilities in the treatment landscape. We look forward to receiving your submissions and appreciate your commitment to advancing the frontiers of medical science.

Dr. Alfredo Caturano
Guest Editor

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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.

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Keywords

cardiovascular diseases
antidiabetic drugs
pharmacological interventions
sodium–glucose cotransporter 2 inhibitors
PCSK9 inhibitors
obeticholic acid
lipid-lowering agents
heart failure treatment
diabetes management
drug therapy innovations

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Advancements in Cardiovascular and Antidiabetic Drug Therapy in Pharmaceuticals (13 articles)

Published Papers (6 papers)

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Research

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16 pages, 575 KiB

Open AccessArticle

Polycystic Ovary Syndrome Attenuates TSH-Lowering Effect of Metformin in Young Women with Subclinical Hypothyroidism

by Robert Krysiak, Karolina Kowalcze, Johannes Ott, Sofia Burgio, Simona Zaami and Bogusław Okopień

Pharmaceuticals 2025, 18(8), 1149; https://doi.org/10.3390/ph18081149 - 1 Aug 2025

Viewed by 205

Abstract

Background/Objectives: The effect of metformin on the secretory function of thyrotropic cells is sex-dependent. The current study aimed to investigate whether the impact of this drug on activity of the hypothalamic–pituitary–thyroid axis in women is impacted by the androgen status of patients. Methods: The study population included 48 levothyroxine-naïve reproductive-aged women with subclinical hypothyroidism and prediabetes receiving 3.0 g of metformin daily. Women with (n = 24) and without (n = 24) polycystic ovary syndrome were matched for age, insulin sensitivity, TSH, and reasons for thyroid hypofunction. Circulating levels of glucose, glycated hemoglobin, insulin, TSH, thyroid hormones, gonadotropins, androgens, estradiol, SHBG, prolactin, ACTH, and IGF-1 were measured before metformin treatment and six months later. Results: At entry, women with and without polycystic ovary syndrome differed in LH, LH/FSH ratio, androgens, and estradiol. The decrease in TSH, fasting glucose and glycated hemoglobin, and the improvement in insulin sensitivity were less pronounced in women with than in women without polycystic ovary syndrome. In each group, there were no differences in the impact on TSH and thyroid hormones between patients with subclinical hypothyroidism of autoimmune and non-autoimmune origin. The changes in TSH inversely correlated with total testosterone and free androgen index. Only in women with coexisting polycystic ovary syndrome, did metformin slightly reduce LH, LH/FSH ratio, testosterone, and free androgen index. Conclusions: The results suggest that concurrent polycystic ovary syndrome attenuates metformin action on TSH secretion, which can be explained by increased androgen production. Moreover, the drug seems to alleviate PCOS-associated changes in the activity of the reproductive axis. Full article

(This article belongs to the Special Issue Advancements in Cardiovascular and Antidiabetic Drug Therapy, 2nd Edition)

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12 pages, 630 KiB

Open AccessArticle

Real-World Analysis of Short-Term Effectiveness of Oral Semaglutide: Impact on Glycometabolic Control and Cardiovascular Risk

by Sara Palazzi, Federica Sentinelli, Antonella Zugaro, Sara Morgante, Livia Santarelli, Sandra Melanzi, Annamaria De Mutiis, Deamaria Piersanti, Barbara Macerola, Marco Iezzi, Pietro Mercuri, Alessandro Ferranti, Daniele Tienforti, Maria Gisella Cavallo, Arcangelo Barbonetti and Marco Giorgio Baroni

Pharmaceuticals 2025, 18(6), 856; https://doi.org/10.3390/ph18060856 - 8 Jun 2025

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Abstract

Background: Oral semaglutide, a GLP1-receptor agonist (GLP1-RA), shows promise in efficacy and compliance, especially amid the global shortage of injectable GLP-1 RAs. Its short-term effectiveness remains unexplored. Objective: This real-world observational study assessed the short-term effectiveness of oral semaglutide after three months of therapy. Methods: Patients with type 2 diabetes from four Italian diabetes centers, who received an initial prescription of oral semaglutide, were reassessed after three months. Primary outcomes included glycated hemoglobin (HbA1c) and body weight reduction; secondary outcomes involved changes in lipid parameters and cardiovascular risk. Results: Among 167 participants (mean age 66.5 years, mostly obese, baseline HbA1c 8.4% ± 1.5), 83.2% received a 7 mg dose. After three months, HbA1c significantly declined (8.4% to 7.1%, −1.3%, p < 0.001), alongside body mass index (BMI) (30.9 kg/m² to 29.6 kg/m², p < 0.0001). The target HbA1c ≤ 7% was achieved by 54.5%, and 34.7% reached ≤6.5%. Patients losing >5% of their initial weight (30.5%) saw the largest HbA1c drop (−1.9%). Those with newly diagnosed diabetes or a duration < 5 years showed superior responses (p = 0.001), while no significant differences were found based on the timing of drug administration. Oral semaglutide replaced or supplemented prior therapies, allowing discontinuation of dipeptidyl peptidase 4 inhibitors (DPP4i), sulfonylureas, glinides, and acarbose, and deprescription of thiazolidinediones. A significant reduction in cardiovascular risk was observed (p = 0.04), together with a significant reduction in lipid parameters. Conclusions: Oral semaglutide showed significant short-term efficacy, reducing HbA1c, body weight, and cardiovascular risk in three months, making it a valuable therapeutic option. Full article

(This article belongs to the Special Issue Advancements in Cardiovascular and Antidiabetic Drug Therapy, 2nd Edition)

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17 pages, 1552 KiB

Open AccessArticle

The Effect of Metformin on Pituitary Function in Postmenopausal Women with Subclinical Hypothyroidism and Macroprolactinemia: A Single-Center Prospective Case–Control Study

by Robert Krysiak, Witold Szkróbka, Karolina Kowalcze and Bogusław Okopień

Pharmaceuticals 2025, 18(6), 834; https://doi.org/10.3390/ph18060834 - 2 Jun 2025

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Abstract

Background/Objectives: Metformin inhibits secretory function of overactive thyrotrophs, gonadotrophs, and lactotrophs. The clinical significance of an excess of high-molecular-weight prolactin (macroprolactinemia) remains unclear. The aim of the current study was to investigate for the first time whether macroprolactinemia determines the pituitary effects of this drug. Methods: This single-center prospective case–control study included two groups of postmenopausal women with subclinical hypothyroidism, who were matched for age, insulin sensitivity, and plasma concentrations of gonadotropins and TSH. Group A enrolled women with normal prolactin status, while group B included women with macroprolactinemia. Owing to concomitant type 2 diabetes or prediabetes, all the participants received metformin for six months. The outcomes of interest included glucose homeostasis markers (fasting glucose, glycated hemoglobin, and HOMA-IR), plasma prolactin (total and monomeric), macroprolactin, other pituitary hormones (FSH, LH, TSH, and ACTH), and peripheral hormones (estradiol, free thyroid hormones, and IGF-1). Results: Before metformin treatment, the study groups differed only in concentrations of total prolactin and macroprolactin. Metformin decreased FSH and TSH and tended to decrease LH only in group A, and the strength of this effect showed correlations with the baseline levels of these hormones, the degree of improvement in insulin sensitivity, and the macroprolactin content (only in group B). The decrease in fasting glucose, glycated hemoglobin, and HOMA-IR was more pronounced in group A than group B. There were no differences between the pretreatment and posttreatment values of total prolactin, monomeric prolactin, macroprolactin, ACTH, estradiol, free thyroid hormones, and IGF-1. Conclusions: The obtained results suggest that macroprolactinemia may counteract the pituitary effects of metformin. Full article

(This article belongs to the Special Issue Advancements in Cardiovascular and Antidiabetic Drug Therapy, 2nd Edition)

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14 pages, 1161 KiB

Open AccessArticle

The Effects of Inclisiran on the Subclinical Inflammatory Markers of Atherosclerotic Cardiovascular Disease in Patients at High Cardiovascular Risk

by Mateusz Maligłówka, Adrianna Dec, Łukasz Bułdak and Bogusław Okopień

Pharmaceuticals 2025, 18(6), 832; https://doi.org/10.3390/ph18060832 - 1 Jun 2025

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Abstract

Background/Objectives: Hypercholesterolemia, accompanied by vascular inflammation, leads to the premature initiation and progression of atherosclerosis, and both are considered nowadays as well-established cardiovascular (CV) risk factors. For several years, proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9is), drugs that reduce the degradation of the receptors for low-density lipoprotein cholesterol (LDLRs), have appeared to be a very efficient lipid-lowering therapy among patients with complications resulting from atherosclerotic cardiovascular disease (ASCVD). Previous studies showed that drugs used to fight hypercholesterolemia (predominantly statins) have significant pleiotropic effects, including anti-inflammatory effects. To date, data on the potential impact of PCSK9 inhibitors, especially inclisiran, on the course of inflammation is still lacking. Therefore, we conceived a study to evaluate the effects of inclisiran on the markers of subclinical inflammation (e.g., pentraxin 3 (PTX3), interleukin-18 (IL-18), and soluble cluster of differentiation 40 ligand (CD40L)) and compared their magnitude in patients at high CV risk, with and without established heterozygous familial hypercholesterolemia (HeFH). Methods: A total of 24 patients at high cardiovascular risk, according to European Society of Cardiology (ESC) guidelines, with or without concomitant HeFH diagnosed using Dutch Lipid Clinic Network (DLCN) criteria, were enrolled in this study. Lipid concentrations and levels of subclinical inflammatory markers of atherosclerosis were measured at the beginning and after 3 months of therapy. Results: After three months of therapy with inclisiran, a statistically significant reduction included total cholesterol (TC): study group 1: from 287.6 ± 94.15 to 215.2 ± 89.08 [mg/dL], p = 0.022 and study group 2: from 211.71 ± 52.72 to 147.64 ± 55.44 [mg/dL], p < 0.001, and low-density lipoprotein cholesterol (LDL-c): study group 1: from 180.79 ± 73.33 to 114.65 ± 71.54 [mg/dL], p = 0.031 and study group 2: from 129.62 ± 46.75 to 63.39 ± 43.6 [mg/dL], p < 0.001. Moreover significant drops were observed in concentrations of PTX3: study group 1: from 1336.33 ± 395.15 to 1121.75 ± 351.17 [pg/mL], p = 0.013 and study group 2: from 1610.76 ± 537.78 to 1376.92 ± 529.19 [pg/mL], p = 0.017), and IL-18: study group 1: from 11.89 (9.72–13.98) to 9.15 (8.62–10.06) [pg/mL], p = 0.005 and study group 2: from 11.58 (10.87–16.97) to 9.65 (8.43–10.95) [pg/mL], p = 0.003). There were no significant changes in the levels of sCD40L. Conclusions: This study confirmed the ability of inclisiran to reduce LDL-c levels in patients at high cardiovascular risk just after one dose of the drug. Furthermore, it appeared that beyond its lipid-lowering effect, the drug may also affect some inflammatory processes involved in the initiation and progression of atherosclerosis. Full article

(This article belongs to the Special Issue Advancements in Cardiovascular and Antidiabetic Drug Therapy, 2nd Edition)

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13 pages, 710 KiB

Open AccessArticle

Evaluating Guideline Alignment by Analyzing Patient Profiles of Elderly People with Type 2 Diabetes and Chronic Kidney Disease Treated or Not with SGLT2 Inhibitors

by Kyriaki Vafeidou, Ourania Psoma, Georgios Dimakopoulos, Evangelos Apostolidis, Anastasia Sarvani, Eleni Gavriilaki, Michael Doumas, Vassilios Tsimihodimos, Kalliopi Kotsa and Theocharis Koufakis

Pharmaceuticals 2025, 18(6), 807; https://doi.org/10.3390/ph18060807 - 27 May 2025

Viewed by 764

Abstract

Background/Objectives: Current guidelines for the management of type 2 diabetes (T2D) strongly recommend the use of sodium–glucose cotransporter 2 inhibitors (SGLT2is) in patients with chronic kidney disease (CKD) to alleviate cardiorenal risk. However, the implementation of this guidance in daily practice remains limited. In a real-world setting, we evaluated the frequency of SGLT2i use in elderly people with T2D and CKD and compared patient profiles between SGLT2i users and non-users. Methods: We retrospectively analyzed the medical records of individuals over 65 years of age followed in outpatient internal medicine clinics in Greece. Demographic and laboratory parameters, comorbidity profiles, and medication use were recorded and compared between the SGLT2i and non-SGLT2i groups. Results: The analysis included 135 patients with T2D and CKD, of whom the majority (57.8%) did not receive SGLT2i treatment. The patients in the SGLT2i group were younger (p = 0.006), had higher creatinine (p = 0.001) and hemoglobin (p = 0.001) values, and lower levels of uric acid (p = 0.025) than the participants not treated with SGLT2is. Heart failure rates were similar between the groups (p = 0.252). There was no difference in the use of renin–angiotensin–aldosterone system inhibitors (p = 0.210); in contrast, treatment with glucagon-like peptide 1 receptor agonists was more frequent in the group receiving SGLT2is compared to the group not treated with gliflozins (p = 0.002). Conclusions: Real-world data confirm the benefits of SGLT2i treatment for elderly people with T2D and CKD. However, our findings indicate that the use of gliflozins in this population of patients remains suboptimal, highlighting the need for greater vigilance among prescribers to align with existing guidelines. Full article

(This article belongs to the Special Issue Advancements in Cardiovascular and Antidiabetic Drug Therapy, 2nd Edition)

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39 pages, 2934 KiB

Open AccessReview

Phytocannabinoids as Novel SGLT2 Modulators for Renal Glucose Reabsorption in Type 2 Diabetes Management

by Raymond Rubianto Tjandrawinata, Dante Saksono Harbuwono, Sidartawan Soegondo, Nurpudji Astuti Taslim and Fahrul Nurkolis

Pharmaceuticals 2025, 18(8), 1101; https://doi.org/10.3390/ph18081101 - 24 Jul 2025

Viewed by 469

Abstract

Background: Sodium–glucose cotransporter 2 (SGLT2) inhibitors have transformed type 2 diabetes mellitus (T2DM) management by promoting glucosuria, lowering glycated hemoglobin (HbA1c), blood pressure, and weight; however, their use is limited by genitourinary infections and ketoacidosis. Phytocannabinoids—bioactive compounds from Cannabis sativa—exhibit multi-target pharmacology, including interactions with cannabinoid receptors, Peroxisome Proliferator-Activated Receptors (PPARs), Transient Receptor Potential (TRP) channels, and potentially SGLT2. Objective: To evaluate the potential of phytocannabinoids as novel modulators of renal glucose reabsorption via SGLT2 and to compare their efficacy, safety, and pharmacological profiles with synthetic SGLT2 inhibitors. Methods: We performed a narrative review encompassing the following: (1) the molecular and physiological roles of SGLT2; (2) chemical classification, natural sources, and pharmacokinetics/pharmacodynamics of major phytocannabinoids (Δ⁹-Tetrahydrocannabinol or Δ⁹-THC, Cannabidiol or CBD, Cannabigerol or CBG, Cannabichromene or CBC, Tetrahydrocannabivarin or THCV, and β-caryophyllene); (3) in silico docking and drug-likeness assessments; (4) in vitro assays of receptor binding, TRP channel modulation, and glucose transport; (5) in vivo rodent models evaluating glycemic control, weight change, and organ protection; (6) pilot clinical studies of THCV and case reports of CBD/BCP; (7) comparative analysis with established synthetic inhibitors. Results: In silico studies identify high-affinity binding of several phytocannabinoids within the SGLT2 substrate pocket. In vitro, CBG and THCV modulate SGLT2-related pathways indirectly via TRP channels and CB receptors; direct IC₅₀ values for SGLT2 remain to be determined. In vivo, THCV and CBD demonstrate glucose-lowering, insulin-sensitizing, weight-reducing, anti-inflammatory, and organ-protective effects. Pilot clinical data (n = 62) show that THCV decreases fasting glucose, enhances β-cell function, and lacks psychoactive side effects. Compared to synthetic inhibitors, phytocannabinoids offer pleiotropic benefits but face challenges of low oral bioavailability, polypharmacology, inter-individual variability, and limited large-scale trials. Discussion: While preclinical and early clinical data highlight phytocannabinoids’ potential in SGLT2 modulation and broader metabolic improvement, their translation is impeded by significant challenges. These include low oral bioavailability, inconsistent pharmacokinetic profiles, and the absence of standardized formulations, necessitating advanced delivery system development. Furthermore, the inherent polypharmacology of these compounds, while beneficial, demands comprehensive safety assessments for potential off-target effects and drug interactions. The scarcity of large-scale, well-controlled clinical trials and the need for clear regulatory frameworks remain critical hurdles. Addressing these aspects is paramount to fully realize the therapeutic utility of phytocannabinoids as a comprehensive approach to T2DM management. Conclusion: Phytocannabinoids represent promising multi-target agents for T2DM through potential SGLT2 modulation and complementary metabolic effects. Future work should focus on pharmacokinetic optimization, precise quantification of SGLT2 inhibition, and robust clinical trials to establish efficacy and safety profiles relative to synthetic inhibitors. Full article

(This article belongs to the Special Issue Advancements in Cardiovascular and Antidiabetic Drug Therapy, 2nd Edition)

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