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Background: SGLT-2 inhibitors, prescribed for type 2 diabetes, have a heightened risk of amputation. The FDA issued a warning in May 2017, leading to the inclusion of a cautionary label. Vigilance is essential for patients and healthcare providers to promptly identify and address potential limb complications associated with the use of SGLT-2 inhibitors.
Method: A comprehensive search of electronic databases was conducted, covering the period from inception to May 2024. This systematic literature review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The quality of the included studies was assessed using the Cochrane risk of bias (ROB) tool. Inclusion and exclusion criteria were predefined, and data extraction was performed to summarize the findings.
Result: A total of 12 randomized control trial (RCT) studies were included in the present systematic review. 37,657 (54.89%) participants were randomly assigned to receive the different interventions of SGLT-2 inhibitor, whereas 30,959 (45.11%) received a placebo. Overall, 618 events were reported in the treatment group, whereas 396 events were reported in the placebo group.
Conclusion: In conclusion, patients treated with SGLT-2 inhibitors did not have any significant difference in amputation occurrences compared to placebo across various studies. However, canagliflozin usage has led to higher amputation events in certain trials.
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http://dx.doi.org/10.1055/a-2366-8999 | DOI Listing |
NMR Biomed
October 2025
High-Field MR Center, Department of Biomedical Imaging and Image-Guided Therapy, Medical University of Vienna, Vienna, Austria.
The human kidneys play a pivotal role in regulating blood pressure, water, and salt homeostasis, but assessment of renal function typically requires invasive methods. Deuterium metabolic imaging (DMI) is a novel, noninvasive technique for mapping tissue-specific uptake and metabolism of deuterium-labeled tracers. This study evaluates the feasibility of renal DMI at 7-Tesla (7T) to track deuterium-labeled tracers with high spatial and temporal resolution, aiming to establish a foundation for potential clinical applications in the noninvasive investigation of renal physiology and pathophysiology.
View Article and Find Full Text PDFG Ital Nefrol
August 2025
UO Nefrologia e Dialisi, Ospedale di Cassino, Italia.
SGLT-2 inhibitors are a relatively new class of antidiabetic drugs. They activate a transcriptional response similar to calorie restriction characterized by the up-regulation of sensors involved in nutrient deprivation, such as SIRT1 and AMPK, and the down-regulation of mTOR, a molecule involved in nutritional excess signaling. The purpose of this review is to illustrate the main pathways of nutrient deprivation: a complex mechanistic framework partly responsible for the cardio-renal benefits that makes these drugs unique.
View Article and Find Full Text PDFCardiovasc Diabetol
September 2025
Computational Biomedicine, Center for Thrombosis and Hemostasis (CTH), Mainz, Germany.
Background: Sodium-glucose cotransporter 2 (SGLT2) inhibitors, such as Empagliflozin, are antidiabetic drugs that reduce glucose levels and have emerged as a promising therapy for patients with heart failure (HF), although the exact molecular mechanisms underlying their cardioprotective effects remain to be fully elucidated. The EmDia study, a randomized, double-blind trial conducted at the University Medical Center of Mainz, has confirmed the beneficial effects of Empagliflozin in HF patients after both one and twelve weeks of treatment. In this work, we aimed to assess whether changes in lipid profiles driven by Empagliflozin use in HF patients in the EmDia trial could assist in gaining a better understanding of its cardioprotective mechanisms.
View Article and Find Full Text PDFMetab Brain Dis
September 2025
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
Acute or chronic liver damage can result in Hepatic Encephalopathy (HE), a potentially fatal neuropsychiatric condition that leads to cerebral and neurological alterations. Dapagliflozin (DAPA), an orally active Sodium/Glucose cotransporter 2 inhibitor with long duration of action. The study aim was to evaluate the potential protective impact of DAPA against HE caused by Thioacetamide (TAA) in rats.
View Article and Find Full Text PDFDrug Dev Res
September 2025
School of Pharmacy, The University of Jordan, Amman, Jordan.
Cancer treatment faces challenges like nonselective toxicity and drug resistance, prompting the need for innovative therapies. This study aimed to develop liposomal formulations for co-delivery of empagliflozin and rutin, evaluating their anticancer and antioxidant efficacy. PEGylated empagliflozin-loaded nanoliposomes (Empa-NLs) and empagliflozin-rutin co-loaded nanoliposomes (Empa-Rut NLs) were synthesized using the thin-film hydration technique.
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