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Pharmaceutics
Special Issues
Effective Therapies for Diabetes
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Effective Therapies for Diabetes

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Clinical Pharmaceutics".

Deadline for manuscript submissions: closed (25 February 2024) | Viewed by 14540

Special Issue Editors

Dr. Miodrag Janić

E-Mail Website
Guest Editor
Department Endocrinology, Diabetes and Metabolic Diseases, University Medical Centre Ljubljana, SI-1000 Ljubljana, Slovenia
Interests: type 2 diabetes; type 1 diabetes; medication-induced diabetes; GLP-1 receptor agonists; GLP-1/GIP dual agonist; SGLT-2 inhibitors; pleiotropic drug effects; cardiovascular complications; prevention of cardiovascular diseases; cardiometabolic diseases; chronic inflammatory diseases
Dr. Mojca Lunder

E-Mail Website
Guest Editor
Department Endocrinology, Diabetes and Metabolic Diseases, University Medical Centre Ljubljana, SI-1000 Ljubljana, Slovenia
Interests: diabetes; type 2 diabetes; type 1 diabetes; other types of diabetes; novel antidiabetic therapies; SGLT-2 inhibitors; GLP-1 receptor agonists; GLP-1/GIP dual agonist; pleiotropic effects; target organ protection; vascular protection; glycemic variability; chronic diabetic complications; microvascular complications; cardiovascular diseases

Special Issue Information

Dear Colleagues,

Treatment of diabetes, particularly type 2 diabetes, is a growing field. In the last decade, we have gone on an interesting path, from glucocentricity to ever-evolving targeted diabetes therapies aimed at the reduction of chronic complications per se, above all, reducing morbidity and mortality from cardiovascular disorders. In recent years, the protection of target organs, particularly cardiovascular and kidney protection, with antidiabetic drugs have been found to be very important regardless of glycemic control. However, as the field evolves, new questions are emerging, and therefore answers are needed. To answer questions from our daily clinical practice and open new ones, we have created this Special Issue.  

This Special Issue will cover a wide range of topics related to diabetes therapies.

  • The effects of antidiabetic drugs on glycemic parameters and beyond;
  • Efficacy and safety of new innovative antidiabetic drug formulations;
  • Diabetes therapy particularly aimed at reducing chronic diabetic complications;
  • The role of antidiabetic therapy in the prevention of macrovascular complications;
  • Mechanisms of action of antidiabetic drugs aimed at reducing chronic diabetic complications;
  • Drug prescription aspects and approaches in diabetes;
  • Treatment of different types of diabetes (beyond type 1 and 2); 
  • New and emerging drugs and technologies in diabetes;
  • Detection and prevention of hypoglycemia, related to drugs and beyond.

Dr. Miodrag Janić
Dr. Mojca Lunder
Guest Editors

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. Pharmaceutics 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

  • antidiabetic drugs
  • new antidiabetic drug formulations
  • cardioprotective action
  • reducing chronic complications in diabetes
  • emerging drugs in diabetes

Published Papers (7 papers)

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Research

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14 pages, 1011 KiB  
Article
Comparative Safety Analysis of Empagliflozin in Type 2 Diabetes Mellitus Patients with Chronic Kidney Disease versus Normal Kidney Function: A Nationwide Cohort Study in Korea
by Ha Young Jang, In-Wha Kim and Jung Mi Oh
Pharmaceutics 2023, 15(10), 2394; https://doi.org/10.3390/pharmaceutics15102394 - 27 Sep 2023
Viewed by 1174
Abstract
Background: Empagliflozin has been shown to reduce cardiovascular morbidity and mortality in patients with type 2 diabetes. Various research on its efficacy in patients with chronic kidney disease (CKD) have been actively conducted. So far, few studies have investigated the safety of these [...] Read more.
Background: Empagliflozin has been shown to reduce cardiovascular morbidity and mortality in patients with type 2 diabetes. Various research on its efficacy in patients with chronic kidney disease (CKD) have been actively conducted. So far, few studies have investigated the safety of these adverse effects specifically in Asians with CKD. We aim to address these safety concerns on a patient population of Asian CKD patients using real-world data. Methods: We conducted a retrospective cohort study using health insurance data from the Korean Health Insurance Review & Assessment Service and compared safety outcomes between empagliflozin and sitagliptin in 26,347 CKD patients diagnosed with diabetes. Adverse outcomes, including major adverse cardiac events (MACEs), all-cause mortality, myocardial infarction (MI), stroke, and hospitalization for heart failure (HHF), among others, were assessed. Results: Among a 1:1 matched cohort (6170 on empagliflozin, 6170 on sitagliptin), empagliflozin was associated with a significant reduction in MACEs, all-cause mortality, MI, hospitalization for unstable angina, coronary revascularization, HHF, hypoglycemic events, and urinary tract infections, but increased the risk of genital tract infections. No significant changes were observed for transient ischemic attack, acute kidney injury, volume depletion, diabetic ketoacidosis, thromboembolic events, and fractures. Conclusions: The usage of empagliflozin in diabetic CKD patients shows a significant reduction in many adverse outcomes compared to sitagliptin, but with an increased risk of genital tract infections. These findings provide evidence for future clinical decision-making around the use of empagliflozin in Asian CKD patients. Full article
(This article belongs to the Special Issue Effective Therapies for Diabetes)
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12 pages, 980 KiB  
Article
Effect of Switching to Once-Weekly Semaglutide on Non-Alcoholic Fatty Liver Disease: The SWITCH-SEMA 1 Subanalysis
by Hiroshi Nomoto, Yuka Takahashi, Yoshinari Takano, Hiroki Yokoyama, Kazuhisa Tsuchida, So Nagai, Aika Miya, Hiraku Kameda, Kyu Yong Cho, Akinobu Nakamura and Tatsuya Atsumi
Pharmaceutics 2023, 15(8), 2163; https://doi.org/10.3390/pharmaceutics15082163 - 20 Aug 2023
Cited by 1 | Viewed by 1528
Abstract
Non-alcoholic fatty liver disease (NAFLD) is an important common comorbidity in individuals with type 2 diabetes (T2DM). Although some glucagon-like peptide-1 receptor agonists (GLP-1RAs) have beneficial effects on NAFLD, the efficacy of once-weekly semaglutide has not been established. This was a subanalysis of [...] Read more.
Non-alcoholic fatty liver disease (NAFLD) is an important common comorbidity in individuals with type 2 diabetes (T2DM). Although some glucagon-like peptide-1 receptor agonists (GLP-1RAs) have beneficial effects on NAFLD, the efficacy of once-weekly semaglutide has not been established. This was a subanalysis of the SWITCH-SEMA 1 study, a multicenter, prospective, randomized, parallel-group trial comparing switching from liraglutide or dulaglutide to once-weekly semaglutide in subjects with T2DM (SWITCH) versus continuing current GLP-1RAs (Continue) for 24 weeks. This subanalysis consisted of participants who were suspected to have NAFLD [fatty liver index (FLI) ≥ 30]. In total, 58 participants met the criteria of this subanalysis. There were no statistical differences in baseline characteristics between the SWITCH (n = 31) and Continue groups (n = 27). FLI significantly improved during treatment in the SWITCH group (68.6 to 62.7) but not in the Continue group (71.1 to 72.3) (p < 0.01). The improvement of FLI in the SWITCH group was greater in switching from dulaglutide to semaglutide and significantly correlated with older age (p = 0.016) and lower baseline FLI (p < 0.01). The multiple linear regression analysis revealed that the switch from dulaglutide was associated with an improvement in FLI (p = 0.041). Switching from conventional GLP-1RAs to once-weekly semaglutide might be beneficial for individuals with NAFLD complicated with T2DM. Full article
(This article belongs to the Special Issue Effective Therapies for Diabetes)
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18 pages, 1077 KiB  
Article
The Effect of Additional Treatment with Empagliflozin or Semaglutide on Endothelial Function and Arterial Stiffness in Subjects with Type 1 Diabetes Mellitus—ENDIS Study
by Maja Preložnik Navodnik, Andrej Janež and Ivan Žuran
Pharmaceutics 2023, 15(7), 1945; https://doi.org/10.3390/pharmaceutics15071945 - 14 Jul 2023
Cited by 2 | Viewed by 1300
Abstract
We investigated the effect of additional treatment with newer antidiabetic drugs on endothelium function and arterial stiffness in subjects with type 1 diabetes mellitus (T1DM) without cardiovascular diseases. A total of 89 participants, all users of CGMS (continuous monitoring glucose system), were randomized [...] Read more.
We investigated the effect of additional treatment with newer antidiabetic drugs on endothelium function and arterial stiffness in subjects with type 1 diabetes mellitus (T1DM) without cardiovascular diseases. A total of 89 participants, all users of CGMS (continuous monitoring glucose system), were randomized into three comparable groups, receiving empagliflozin (E; n = 30), receiving semaglutide (S; n = 30), and a control group (C; n = 29). At baseline and 12 weeks post treatment, we measured FMD (brachial artery flow-mediated dilation) and FBF (forearm blood flow as reactive hyperemia assessed with strain gauge plethysmography) as parameters of endothelial function, as well as pulse wave velocity (PWV) and peripheral resistance as parameters of arterial stiffness. Improvement in FMD was significant in both intervention groups compared to controls (E group 2.0-fold, p = 0.000 and S group 1.9-fold, p = 0.000), with no changes between those two groups (p = 0.745). During the evaluation of FBF, there were statistically insignificant improvements in both therapeutic groups compared to controls (E group 1.39-fold, p = 0.074 and S group 1.22-fold, p = 0.701). In arterial stiffness parameters, improvements were seen only in the semaglutide group, with a decline in peripheral resistance by 5.1% (p = 0.046). We can conclude that, for arterial stiffness, semaglutide seems better, but both drugs positively impact endothelial function and, thus, could also have a protective role in T1DM. Full article
(This article belongs to the Special Issue Effective Therapies for Diabetes)
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10 pages, 1010 KiB  
Article
Favorable Effect of Pemafibrate on Insulin Resistance and β-Cell Function in Subjects with Type 2 Diabetes and Hypertriglyceridemia: A Subanalysis of the PARM-T2D Study
by Hiroshi Nomoto, Kenichi Kito, Hiroshi Iesaka, Yuki Oe, Shinichiro Kawata, Kazuhisa Tsuchida, Shingo Yanagiya, Aika Miya, Hiraku Kameda, Kyu Yong Cho, Ichiro Sakuma, Naoki Manda, Akinobu Nakamura and Tatsuya Atsumi
Pharmaceutics 2023, 15(7), 1838; https://doi.org/10.3390/pharmaceutics15071838 - 27 Jun 2023
Viewed by 1052
Abstract
Pemafibrate, a novel selective peroxisome proliferator-activated receptor modulator, has beneficial effects on lipid metabolism. However, its effects on glucose metabolism in individuals with type 2 diabetes (T2DM) remain to be fully clarified. This was a subanalysis of the PARM-T2D study, a multicenter prospective [...] Read more.
Pemafibrate, a novel selective peroxisome proliferator-activated receptor modulator, has beneficial effects on lipid metabolism. However, its effects on glucose metabolism in individuals with type 2 diabetes (T2DM) remain to be fully clarified. This was a subanalysis of the PARM-T2D study, a multicenter prospective observational study on the use of pemafibrate versus conventional therapy for 52 weeks in subjects with T2DM complicated with hypertriglyceridemia. The subanalysis included participants who did not change their treatment for diabetes and did not receive insulin or insulin secretagogues during the study period. Changes in glucose metabolism markers, including homeostatic model assessment (HOMA2) scores and disposition index, were assessed. A total of 279 participants (141 in the pemafibrate group; 138 in the control group) met the criteria for the subanalysis. There were no significant changes in HbA1c during the 52-week study period in both groups. However, the pemafibrate group showed significant improvements versus the control group for insulin resistance assessed by HOMA2-R (−0.15 versus 0.08; estimated treatment difference −0.23 (95% confidence interval −0.44, −0.02); p = 0.03) and maintenance of β-cell function assessed by disposition index (0.015 versus −0.023; estimated treatment difference 0.037 (95% confidence interval 0.005, 0.069); p = 0.02). Correlation analyses showed that improvements in HOMA2-R and disposition index were significantly associated with improvements in lipid abnormalities and γ-glutamyl transpeptidase. In conclusion, pemafibrate reduced insulin resistance and maintained β-cell function in subjects with T2DM and hypertriglyceridemia, presumably by improving lipid profiles and lipid-related hepatocyte stress. Full article
(This article belongs to the Special Issue Effective Therapies for Diabetes)
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Review

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20 pages, 1926 KiB  
Review
SGLT2 Inhibitors in the Treatment of Diabetic Kidney Disease: More than Just Glucose Regulation
by Jasna Klen and Vita Dolžan
Pharmaceutics 2023, 15(7), 1995; https://doi.org/10.3390/pharmaceutics15071995 - 20 Jul 2023
Cited by 6 | Viewed by 4469
Abstract
Diabetic kidney disease (DKD) is a severe and common complication and affects a quarter of patients with type 2 diabetes mellitus (T2DM). Oxidative stress and inflammation related to hyperglycemia are interlinked and contribute to the occurrence of DKD. It was shown that sodium–glucose [...] Read more.
Diabetic kidney disease (DKD) is a severe and common complication and affects a quarter of patients with type 2 diabetes mellitus (T2DM). Oxidative stress and inflammation related to hyperglycemia are interlinked and contribute to the occurrence of DKD. It was shown that sodium–glucose cotransporter-2 (SGLT2) inhibitors, a novel yet already widely used therapy, may prevent the development of DKD and alter its natural progression. SGLT2 inhibitors induce systemic and glomerular hemodynamic changes, provide metabolic advantages, and reduce inflammatory and oxidative stress pathways. In T2DM patients, regardless of cardiovascular diseases, SGLT2 inhibitors may reduce albuminuria, progression of DKD, and doubling of serum creatinine levels, thus lowering the need for kidney replacement therapy by over 40%. The molecular mechanisms behind these beneficial effects of SGLT2 inhibitors extend beyond their glucose-lowering effects. The emerging studies are trying to explain these mechanisms at the genetic, epigenetic, transcriptomic, and proteomic levels. Full article
(This article belongs to the Special Issue Effective Therapies for Diabetes)
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Graphical abstract

25 pages, 1398 KiB  
Review
Incretins-Based Therapies and Their Cardiovascular Effects: New Game-Changers for the Management of Patients with Diabetes and Cardiovascular Disease
by Federico Bernardini, Annunziata Nusca, Federica Coletti, Ylenia La Porta, Mariagrazia Piscione, Francesca Vespasiano, Fabio Mangiacapra, Elisabetta Ricottini, Rosetta Melfi, Ilaria Cavallari, Gian Paolo Ussia and Francesco Grigioni
Pharmaceutics 2023, 15(7), 1858; https://doi.org/10.3390/pharmaceutics15071858 - 01 Jul 2023
Cited by 2 | Viewed by 1921
Abstract
Atherosclerosis is the leading cause of death worldwide, especially in patients with type 2 diabetes mellitus (T2D). GLP-1 receptor agonists and DPP-4 inhibitors were demonstrated to play a markedly protective role for the cardiovascular system beyond their glycemic control. Several cardiovascular outcome trials [...] Read more.
Atherosclerosis is the leading cause of death worldwide, especially in patients with type 2 diabetes mellitus (T2D). GLP-1 receptor agonists and DPP-4 inhibitors were demonstrated to play a markedly protective role for the cardiovascular system beyond their glycemic control. Several cardiovascular outcome trials (CVOT) reported the association between using these agents and a significant reduction in cardiovascular events in patients with T2D and a high cardiovascular risk profile. Moreover, recent evidence highlights a favorable benefit/risk profile in myocardial infarction and percutaneous coronary revascularization settings. These clinical effects result from their actions on multiple molecular mechanisms involving the immune system, platelets, and endothelial and vascular smooth muscle cells. This comprehensive review specifically concentrates on these cellular and molecular processes mediating the cardiovascular effects of incretins-like molecules, aiming to improve clinicians’ knowledge and stimulate a more extensive use of these drugs in clinical practice as helpful cardiovascular preventive strategies. Full article
(This article belongs to the Special Issue Effective Therapies for Diabetes)
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28 pages, 2637 KiB  
Review
Mesenchymal Stem Cell-Derived Extracellular Vesicles: A Potential Therapy for Diabetes Mellitus and Diabetic Complications
by Fengtian Sun, Yuntong Sun, Feng Wu, Wenrong Xu and Hui Qian
Pharmaceutics 2022, 14(10), 2208; https://doi.org/10.3390/pharmaceutics14102208 - 17 Oct 2022
Cited by 9 | Viewed by 2212
Abstract
As a novel cell-free strategy, mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) inherit the therapeutic potential of donor cells, and are widely used for the treatment of many diseases. Increasing studies have shown that MSC-EVs transfer various bioactive molecules to create a beneficial microenvironment, [...] Read more.
As a novel cell-free strategy, mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) inherit the therapeutic potential of donor cells, and are widely used for the treatment of many diseases. Increasing studies have shown that MSC-EVs transfer various bioactive molecules to create a beneficial microenvironment, thus exerting protective roles in diabetic mellitus (DM) and diabetic complications. To overcome the limitations of natural MSC-EVs such as heterogeneity and insufficient function, several modification methods have been established for constructing engineered MSC-EVs with elevated repairing efficiency. In this review, the PubMed library was searched from inception to August 2022, using a combination of Medical Subject Headings (MeSH) and keywords related to MSC-EVs, DM, and diabetic complications. We provide an overview of the major characteristics of MSC-EVs and summarize the recent advances of MSC-EV-based therapy for hyperglycemia-induced tissue damage with an emphasis on MSC-EV-mediated delivery of functional components. Moreover, the potential applications of engineered MSC-EVs in DM-related diseases therapy are discussed by presenting examples, and the opportunities and challenges for the clinical translation of MSC-EVs, especially engineered MSC-EVs, are evaluated. Full article
(This article belongs to the Special Issue Effective Therapies for Diabetes)
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