SGLT2 Inhibitors: The Next Blockbuster Multifaceted Drug?

Chan, Jonathan Ch; Chan, Michael

doi:10.3390/medicina59020388

Cited by 5 publications

(3 citation statements)

References 61 publications

(71 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition to their preventive effect in T2DM, SGLT2i are also nephroprotective in non-diabetic patients, which further reduces cardiovascular complications, because CKD is a major risk factor for CVD. In conclusion, these new glucose-lowering drugs, especially SGLT2i and GLP1-RA, have opened a range of treatment options not only for T2DM but also for CKD and CVD, including their simultaneous presence in cardiorenal syndrome [29,152]. Elucidation of the pathomechanistic processes underlying the clinically seen beneficial effects of these drugs may improve understanding and influence further therapeutic applications.…”

Section: Discussionmentioning

confidence: 99%

An Overview of the Cardioprotective Effects of Novel Antidiabetic Classes: Focus on Inflammation, Oxidative Stress, and Fibrosis

Balogh

Wagner

Fekete

2023

IJMS

View full text Add to dashboard Cite

Metabolic diseases, particularly diabetes mellitus (DM), are significant global public health concerns. Despite the widespread use of standard-of-care therapies, cardiovascular disease (CVD) remains the leading cause of death among diabetic patients. Early and evidence-based interventions to reduce CVD are urgently needed. Large clinical trials have recently shown that sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) ameliorate adverse cardiorenal outcomes in patients with type 2 DM. These quite unexpected positive results represent a paradigm shift in type 2 DM management, from the sole importance of glycemic control to the simultaneous improvement of cardiovascular outcomes. Moreover, SGLT2i is also found to be cardio- and nephroprotective in non-diabetic patients. Several mechanisms, which may be potentially independent or at least separate from the reduction in blood glucose levels, have already been identified behind the beneficial effect of these drugs. However, there is still much to be understood regarding the exact pathomechanisms. This review provides an overview of the current literature and sheds light on the modes of action of novel antidiabetic drugs, focusing on inflammation, oxidative stress, and fibrosis.

show abstract

Section: Discussionmentioning

confidence: 99%

An Overview of the Cardioprotective Effects of Novel Antidiabetic Classes: Focus on Inflammation, Oxidative Stress, and Fibrosis

Balogh

Wagner

Fekete

2023

IJMS

View full text Add to dashboard Cite

show abstract

“…CIMT is commonly tested in the carotid arteries [81], as it is a significant indication of early atherosclerosis. I. Feinkohl et al [82,83] report that cIMT is also a significant predictor of cognitive decline in T2DM patients. Future research should assess the therapeutic significance of SGLT2 inhibitors' capacity to minimise atherosclerotic lesions and the consequent impact on cognitive functions.…”

Section: Discussionmentioning

confidence: 99%

Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitors: Harms or Unexpected Benefits?

et al. 2023

View full text Add to dashboard Cite

There is a need for innovative pharmaceutical intervention in light of the increasing prevalence of metabolic disease and cardiovascular disease. The kidneys’ sodium-glucose cotransporter 2 inhibitors (SGLT2) receptors are targeted to reduce glucose reabsorption by SGLT2. Patients with type 2 diabetes mellitus (T2DM) benefit the most from reduced blood glucose levels, although this is just one of the numerous physiological consequences. To establish existing understanding and possible advantages and risks for SGLT2 inhibitors in clinical practice, this article will explore the influence of SGLT2 inhibitors on six major organ systems. In addition, this literature review will discuss the benefits and potential drawbacks of SGLT2 inhibitors on various organ systems and their potential application in therapeutic settings.

show abstract

“…SGLT2i are a class of antihyperglycemic agents that modulate sodium-glucose transport proteins, expressed primarily in segments 1 and 2 of the renal proximal convoluted tubules, lowering the renal threshold for glucose, reducing the reabsorption of filtered glucose and promoting urinary glucose excretion [18,19]. These drugs represent a new therapeutic strategy for diabetes, cardiovascular and renal diseases [20]. The mechanistic pathways and molecular targets of these compounds are not yet completely defined, making it even more significant to advance further insight into the action of SGLT2i, especially by searching for new mechanisms that have not yet been considered.…”

Section: Introductionmentioning

confidence: 99%

Preclinical Studies of Canagliflozin, a Sodium-Glucose Co-Transporter 2 Inhibitor, and Donepezil Combined Therapy in Alzheimer’s Disease

Stanciu,

Ababei,

Solcan

et al. 2023

Pharmaceuticals

View full text Add to dashboard Cite

The incidence of neurodegenerative diseases, such as Alzheimer’s disease (AD), is continuously growing worldwide, which leads to a heavy economic and societal burden. The lack of a safe and effective causal therapy in cognitive decline is an aggravating factor and requires investigations into the repurposing of commonly used drugs. Sodium-glucose co-transporter 2 inhibitors (SGLT2i) are a new and efficient class of hypoglycemic drugs and, due to their pleiotropic effects, have indications that go beyond diabetes. There is emerging data from murine studies that SGLT2i can cross the blood–brain barrier and may have neuroprotective effects, such as increasing the brain-derived neurotrophic factor (BDNF), reducing the amyloid burden, inhibiting acetylcholinesterase (AChE) and restoring the circadian rhythm in the mammalian target of rapamycin (mTOR) activation. The current study investigates the effect of an SGLT2i and donepezil, under a separate or combined 21-day treatment on AD-relevant behaviors and brain pathology in mice. The SGLT2i canagliflozin was found to significantly improve the novelty preference index and the percentage of time spent in the open arms of the maze in the novel object recognition and elevated plus maze test, respectively. In addition, canagliflozin therapy decreased AChE activity, mTOR and glial fibrillary acidic protein expression. The results also recorded the acetylcholine M1 receptor in canagliflozin-treated mice compared to the scopolamine group. In the hippocampus, the SGLT2i canagliflozin reduced the microgliosis and astrogliosis in males, but not in female mice. These findings emphasize the value of SGLT2i in clinical practice. By inhibiting AChE activity, canagliflozin represents a compound that resembles AD-registered therapies in this respect, supporting the need for further evaluation in dementia clinical trials.

show abstract

SGLT2 Inhibitors: The Next Blockbuster Multifaceted Drug?

Cited by 5 publications

References 61 publications

An Overview of the Cardioprotective Effects of Novel Antidiabetic Classes: Focus on Inflammation, Oxidative Stress, and Fibrosis

An Overview of the Cardioprotective Effects of Novel Antidiabetic Classes: Focus on Inflammation, Oxidative Stress, and Fibrosis

Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitors: Harms or Unexpected Benefits?

Preclinical Studies of Canagliflozin, a Sodium-Glucose Co-Transporter 2 Inhibitor, and Donepezil Combined Therapy in Alzheimer’s Disease

Contact Info

Product

Resources

About