Sodium-Glucose Cotransporter 2 (SGLT-2) Inhibitors: Delving Into the Potential Benefits of Cardiorenal Protection Beyond the Treatment of Type-2 Diabetes Mellitus

Srinivas, Natasha; Sarnaik, Mubashira K; Modi, Srimy; Pisipati, Yasaswi; Vaidya, Sarayoo; Gaggatur, Naqvi Syed; Sange, Aliya H; Sange, Ibrahim

doi:10.7759/cureus.16868

Cited by 14 publications

(11 citation statements)

References 49 publications

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“…Sodium-glucose cotransporter 2 inhibitors upgrade glycemic regulation by promoting the elimination of glucose via the kidneys [ 96 ]. Glucosuria is caused by the inhibition of the SGLT2 cotransporter.…”

Section: Discussionmentioning

confidence: 99%

Interactions between Gut Microbiota and Oral Antihyperglycemic Drugs: A Systematic Review

Mindrescu,

Guja,

Jinga

et al. 2024

IJMS

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The intestinal microbiota refers to the collection of microorganisms that exist in the human gut. It has been said that bacteria influence the development of metabolic diseases, such as diabetes mellitus, as they have roles in immunomodulation, protection against pathogens, blood vessel growth, repairing the intestinal wall, and the development of the neurological system. In this review, we look at the latest research regarding interactions between gut microbiota and oral antihyperglycemic drugs and we present data suggesting that the microbiome may help counteract the reduced glucose tolerance and insulin resistance associated with metabolic disorders. We found that antidiabetic drugs can have significant impacts on gut microbiota composition and function, potentially influencing both the efficacy and side effects of these medications. Additionally, we discovered that microbial-based therapeutics, including probiotics, prebiotics, and postbiotics, and fecal microbiota can be considered when discussing preventive measures and personalized treatment options for type 2 diabetes mellitus. Understanding how antidiabetic drugs modulate gut microbiota composition and function is essential for optimizing their therapeutic efficacy and minimizing potential adverse effects. The relationship between the gut microbiota and glycemic agents, not fully understood, is currently the subject of increasing research and discussion. It has been proven that the microbiome can impact the effectiveness of the medications, but further research in this field may uncover novel therapeutic strategies for diabetes and other metabolic disorders by targeting the gut microbiota.

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Section: Discussionmentioning

confidence: 99%

Interactions between Gut Microbiota and Oral Antihyperglycemic Drugs: A Systematic Review

Mindrescu,

Guja,

Jinga

et al. 2024

IJMS

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show abstract

“…In addition, SGLT-2i act as a blocker for sodium-hydrogen exchanger in the heart, increasing mitochondrial calcium and decreasing cytoplasmic sodium and calcium levels. In this way, the antioxidant capacity of the mitochondria is improved, and patients will be at a reduced risk of developing cardiac fibrosis and systolic dysfunction [ 33 ].…”

Section: Reviewmentioning

confidence: 99%

The Roles of Glucagon-Like Peptide 1 (GLP-1) Receptor Agonists and Sodium-Glucose Cotransporter 2 (SGLT-2) Inhibitors in Decreasing the Occurrence of Adverse Cardiorenal Events in Patients With Type 2 Diabetes

Shami¹,

Sousou²,

Batarseh³

et al. 2023

Cureus

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Diabetes mellitus is a metabolic disorder characterized by increased serum glucose due to errors in insulin production or response. The prevalence of diabetes mellitus has continued to rise globally over the years, with roughly 7079 persons per 100,000 expected to be impacted by 2030. A vast number of patients with diabetes mellitus experience unfavorable side effects such as weight gain, hypoglycemia, and hepatorenal toxicity from the several diabetic medications available. These adverse effects may result in life-threatening consequences with a high likelihood of occurrence; therefore, ongoing efforts continue to develop medications with improved tolerability and better glycemic control. Glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium-glucose cotransporter 2 inhibitors (SGLT-2i) are examples of new innovative targeted therapies to manage diabetes mellitus and potentially improve cardiorenal conditions. This review article details the specific mechanisms of action, potential side effects, and cardiorenal benefits of GLP-1RA and SGLT-2i therapies to fully understand their roles in combating type 2 diabetes mellitus (T2D).

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“…SGLT-2 inhibitors prevent both renal damage and the onset of chronic kidney disease in addition to their glucose-lowering Figure 3. Potential mechanisms of SGLT2 inhibitors-induced renoprotection [29].…”

Section: Role Of Sglt-2i In Diabetic Nephropathymentioning

confidence: 99%

“…Multiple mechanisms that contribute to nephroprotective effects of SGLT2-Is in T2D patients may not only include glucose lowering-dependent but also glucose loweringindependent mechanisms (figure 3). These include: (1) Restoration of the tubule-glomerular feedback by increasing sodium delivery at macula densa, leading to afferent arteriolar constriction and reduced glomerular hyperfiltration, (2) Decreased activation of the intra-renal RAAS, which also contributes to reducing glomerular hyperfiltration, (3) Increased production of ketone bodies, which serves as an alternate fuel for adenosine triphosphate production in mitochondria, which helps in attenuating inflammation and (4) Protection against hypoxia, oxidative stress, and fibrosis 28,29 .…”

Section: Role Of Sglt-2i In Diabetic Nephropathymentioning

confidence: 99%

Can DPP-4 Enhibitors and SGLT-2 Inhibitors Pleotropic Effects be Extended to Treat Diabetic Nephropathy?

Faruqui

2023

J. Medicine

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Impaired insulin secretion and resistance remain the core defects in T2DM, but at least six other pathophysiological abnormalities contribute to the dysregulation of glucose metabolism. Diabetic nephropathy is one of the most common microvascular complications and a major cause of end-stage renal disease. Despite many treatment options available, diabetic kidney disease continues to affect a large population with diabetes. The kidneys have the highest DPP-4 expression level in mammalians. DPP- 4 is expressed in several segments of the nephron and the tubule interstitium, placing it at the nexus of inflammation, immune system activation, glomerular and proximal tubular function, salt regulation, and kidney fibrosis. Moreover, DPP-4 expression and urinary activity are up-regulated in diabetic nephropathy, highlighting its role as a potential target to manage diabetic nephropathy. DPP-4 inhibition is associated with mitigation of diabetic and hypertensive renal injury and protection of renal function. Renal glucose reabsorption by SGLT proteins is a critical component of glycemic regulation. SGLT2 protein expression is increased in human diabetic nephropathy even with advanced kidney disease indicating that SGLT2 can be an effective target in treatment of diabetic nephropathy. This review article discusses roles played by DPP-4 inhibitors and SGLT-2 inhibitors alone and in combination in diabetic nephropathy supported by clinical evidences. MEDLINE and EMBASE were searched through September 2022. Randomized controlled trials published in English that evaluated SGLT2 inhibitors and/or DPP4 inhibitors in patients with T2DM were selected. J MEDICINE 2023; 24: 43-49

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Sodium-Glucose Cotransporter 2 (SGLT-2) Inhibitors: Delving Into the Potential Benefits of Cardiorenal Protection Beyond the Treatment of Type-2 Diabetes Mellitus

Cited by 14 publications

References 49 publications

Interactions between Gut Microbiota and Oral Antihyperglycemic Drugs: A Systematic Review

Interactions between Gut Microbiota and Oral Antihyperglycemic Drugs: A Systematic Review

The Roles of Glucagon-Like Peptide 1 (GLP-1) Receptor Agonists and Sodium-Glucose Cotransporter 2 (SGLT-2) Inhibitors in Decreasing the Occurrence of Adverse Cardiorenal Events in Patients With Type 2 Diabetes

Can DPP-4 Enhibitors and SGLT-2 Inhibitors Pleotropic Effects be Extended to Treat Diabetic Nephropathy?

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