The protective effects of SGLT-2 inhibitors, GLP-1 receptor agonists, and RAAS blockers against renal injury in patients with type 2 diabetes

Kuang, Zengguang; Hou, Ningning; Kan, Chengxia; Han, Fang; Qiu, Hongyan; Sun, Xiaodong

doi:10.1007/s11255-022-03355-6

Cited by 6 publications

(3 citation statements)

References 111 publications

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“…A variety of hypoglycemic drugs have shown protective effects on chronic diabetic kidney disease ( Kuang et al, 2023 ), but the mechanisms involved are still unclear. Consistent with previous studies ( Cha et al, 2021 ), this study showed that liraglutide and empagliflozin not only reduced blood glucose, but also improved diabetes-related kidney damage.…”

Section: Discussionmentioning

confidence: 99%

Comparing the effects of empagliflozin and liraglutide on lipid metabolism and intestinal microflora in diabetic mice

Yang,

Deng,

Feng

et al. 2024

PeerJ

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Background and Objectives Recent studies have shown that the imbalance of intestinal flora is related to the occurrence and progression of diabetic nephropathy (DN) and can affect lipid metabolism. Sodium-dependent glucose transporters 2 (SGLT2) inhibitor and glucagon-like peptide-1 (GLP-1) receptor agonist are commonly used hypoglycemic drugs and have excellent renal safety. The purpose of this study was to compare the protective effects of empagliflozin and liraglutide on kidneys, lipid metabolism, and intestinal microbiota in diabetic mice. Methods We established a mouse model of type two diabetes by feeding rats a high-fat diet (HFD) followed by an intraperitoneal injection of STZ. The mice were randomly divided into groups: normal control (NC), diabetic model (DM), liraglutide treatment (LirT), empagliflozin treatment (EmpT), and liraglutide combined with empagliflozin treatment (Emp&LirT) groups. Blood glucose, lipids, creatinine, and uric acid, as well as urinary nitrogen and albumin levels were measured. The renal tissues were subjected to HE, PAS and Masson’s staining. These parameters were used to evaluate renal function and histopathological changes in mice. Mice feces were also collected for 16sRNA sequencing to analyze the composition of the intestinal flora. Results All the indexes related to renal function were significantly improved after treatment with drugs. With respect to lipid metabolism, both drugs significantly decreased the serum triglyceride levels in diabetic mice, but the effect of liraglutide on reducing serum cholesterol was better than that of empagliflozin. However, empagliflozin had a better effect on the reduction of low-density lipoproteins (LDL). The two drugs had different effects on intestinal flora. At the phylum level, empagliflozin significantly reduced the ratio of Firmicutes to Bacteroidota, but no effect was seen with liraglutide. At the genus level, both of them decreased the number of Helicobacter and increased the number of Lactobacillus. Empagliflozin also significantly increased the abundance of Muribaculaceae, Muribaculum, Olsenella, and Odoribacter, while liraglutide significantly increased that of Ruminococcus. Conclusion Liraglutide and empagliflozin were both able to improve diabetes-related renal injury. However, the ability of empagliflozin to reduce LDL was better compared to liraglutide. In addition, their effects on the intestine bacterial flora were significantly different.

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Section: Discussionmentioning

confidence: 99%

Comparing the effects of empagliflozin and liraglutide on lipid metabolism and intestinal microflora in diabetic mice

Yang,

Deng,

Feng

et al. 2024

PeerJ

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“…The renin-angiotensin-aldosterone system is positively correlated with T2D and hypertension [196][197][198][199]. Anti-hypertensive medications that block the RAAS have been evidenced to have osteoprotective effects [3,[200][201][202][203][204][205]. Furthermore, RAAS blockers are directly correlated with improved glucose handling and inhibition of progressive insulin resistance [199,206].…”

Section: Discussionmentioning

confidence: 99%

The Relationship between Renin–Angiotensin–Aldosterone System (RAAS) Activity, Osteoporosis and Estrogen Deficiency in Type 2 Diabetes

Mkhize

Mosili

Ngubane

et al. 2023

IJMS

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Type 2 diabetes (T2D) is associated with a plethora of comorbidities, including osteoporosis, which occurs due to an imbalance between bone resorption and formation. Numerous mechanisms have been explored to understand this association, including the renin–angiotensin–aldosterone system (RAAS). An upregulated RAAS has been positively correlated with T2D and estrogen deficiency in comorbidities such as osteoporosis in humans and experimental studies. Therefore, research has focused on these associations in order to find ways to improve glucose handling, osteoporosis and the downstream effects of estrogen deficiency. Upregulation of RAAS may alter the bone microenvironment by altering the bone marrow inflammatory status by shifting the osteoprotegerin (OPG)/nuclear factor kappa-Β ligand (RANKL) ratio. The angiotensin-converting-enzyme/angiotensin II/Angiotensin II type 1 receptor (ACE/Ang II/AT1R) has been evidenced to promote osteoclastogenesis and decrease osteoblast formation and differentiation. ACE/Ang II/AT1R inhibits the wingless-related integration site (Wnt)/β-catenin pathway, which is integral in bone formation. While a lot of literature exists on the effects of RAAS and osteoporosis on T2D, the work is yet to be consolidated. Therefore, this review looks at RAAS activity in relation to osteoporosis and T2D. This review also highlights the relationship between RAAS activity, osteoporosis and estrogen deficiency in T2D.

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“…The primary mechanism by which all of this is accomplished is through attenuating the effects of angiotensin II [40]. RAAS blockers have been shown to boost insulin sensitivity, leading to a reduction in insulin resistance as well as associated inflammation [41].…”

Section: Blocking the Raas And Its Clinical Applicationsmentioning

confidence: 99%

Slowing the Progression of Diabetic Kidney Disease

Blazek,

Bakris

2023

Cells

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Diabetes is the most frequent cause of kidney disease that progresses to end-stage renal disease worldwide, and diabetic kidney disease is significantly related to unfavorable cardiovascular outcomes. Since the 1990s, specific therapies have emerged and been approved to slow the progression of diabetic kidney disease, namely, renin–angiotensin–aldosterone system blockers (including angiotensin-converting enzyme inhibitors (ACEi) angiotensin receptor blockers (ARBs), the non-steroidal mineralocorticoid receptor antagonist (NS-MRA), finerenone, and sodium–glucose cotransporter-2 (SGLT2) inhibitors). Mechanistically, these different classes of agents bring different anti-inflammatory, anti-fibrotic, and complementary hemodynamic effects to patients with diabetic kidney disease such that they have additive benefits on slowing disease progression. Within the coming year, there will be data on renal outcomes using the glucagon-like peptide-1 receptor agonist, semaglutide. All the aforementioned medications have also been shown to improve cardiovascular outcomes. Thus, all three classes (maximally dosed ACEi or ARB, low-dose SGLT-2 inhibitors, and the NS-MRA, finerenone) form the “pillars of therapy” such that, when used together, they maximally slow diabetic kidney disease progression. Ongoing studies aim to expand these pillars with additional medications to potentially normalize the decline in kidney function and reduce associated cardiovascular mortality.

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The protective effects of SGLT-2 inhibitors, GLP-1 receptor agonists, and RAAS blockers against renal injury in patients with type 2 diabetes

Cited by 6 publications

References 111 publications

Comparing the effects of empagliflozin and liraglutide on lipid metabolism and intestinal microflora in diabetic mice

Comparing the effects of empagliflozin and liraglutide on lipid metabolism and intestinal microflora in diabetic mice

The Relationship between Renin–Angiotensin–Aldosterone System (RAAS) Activity, Osteoporosis and Estrogen Deficiency in Type 2 Diabetes

Slowing the Progression of Diabetic Kidney Disease

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