GLP-1Ra can not only lower blood sugar and protect kidneys, but may also help new crown patients?

In addition to abnormal renal function and blood sugar, patients with diabetic nephropathy (DKD) often have chronic inflammation, and the risk of major adverse cardiovascular events (MACEs) is much higher than that of healthy people
.

Recently, outbreaks have been repeated, and some critically ill patients have diabetes or chronic kidney disease (CKD)¹
.

 On March 12, 2022, a review from the Cannizzaro Hospital in Italy was published in CKJ, which combined existing clinical and animal test data and concluded that glucagon-like peptide-1 receptor agonists (GLP) -1Ra) can effectively control sugar, protect the kidney, protect the heart and reduce the risk of adverse events, and may have anti-inflammatory effects in diabetic patients with COVID-19 disease²! This article mainly excerpts the pharmacological effects of GLP-1Ra, the effects of glucose control and kidney protection, and the anti-inflammatory and metabolic effects on patients with COVID-19 for reference by clinicians
.

Pharmacological effects of GLP-1Ra In general, the pharmacological effects of GLP-1Ra are mainly aimed at four aspects: stimulating insulin secretion, suppressing appetite, slowing metabolism and promoting weight loss
.

 ① GLP-1Ra stimulates insulin secretion and inhibits glucagon secretion in a glucose concentration-dependent manner to exert hypoglycemic effect, and can also promote β-cell proliferation, inhibit β-cell apoptosis and increase somatostatin release; ② suppress appetite by interacting with Hunger regulates neural interactions to increase satiety, thereby suppressing appetite; ③ slowing metabolism is associated with inhibiting hepatic gluconeogenesis, reducing hepatic steatosis and fibrosis, slowing gastric emptying and small intestinal motility; ④ promoting weight loss and increasing brown fat The metabolism of tissue cells is closely related to the reduction of lipid deposition in white adipose tissue cells
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In addition to the well-known sugar control effect, GLP-1Ra can also protect the kidney
.

This is not only related to the fact that GLP-1Ra promotes weight loss and blood sugar control, but also that GLP-1Ra can directly act on kidney cells
.

Numerous human studies have shown that GLP-1R is present in glomeruli and tubules, and GLP-1Ra appears to counteract glomerular hyperfiltration
.

Kim et al.
demonstrated that liraglutide can increase the secretion of atrial natriuretic peptide (ANP) to promote natriuresis
.

Thus, the blood pressure-lowering effect of GLP-1Ra is partially explained
.

In addition, GLP-1Ra inhibits mesangial expansion, reduces the expression of pro-fibrotic molecules in endothelial cells, and increases the availability of nitric oxide in the glomerulus, thereby slowing the progression of DKD
.

 Other scholars have proposed through studies that GLP-1Ra can protect the kidneys through anti-atherosclerotic properties, including reducing intestinal chylomicron production and secretion, and reducing total cholesterol, LDL cholesterol and triglyceride levels; Modulates mitochondrial activity in renal cells to reduce ischemic injury; and reduces renal oxidative stress
.

02Clinical evidence From the perspective of pharmacological effects, GLP-1Ra may have a renal protective effect
.

Meanwhile, the renal benefit of GLP-1Ra in patients with DKD is supported by numerous trials
.

 ① LEADER trial In the LEADER trial, the enrolled patients were 9340 diabetic patients with high risk or known cardiovascular disease, and were randomly assigned to the liraglutide group and the placebo group
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The primary endpoint was MACEs, and secondary endpoints were a composite of renal events (macroalbuminuria, doubling of creatinine or eGFR <45 ml/min/1.
73 m2, and need for dialysis and renal death), all-cause death, and retinopathy
.

 Patients in the liraglutide group had an average 0.
4% reduction in glycated hemoglobin levels and an average weight loss of 2.
3 kg
.

The incidence of MACEs in the liraglutide group (13%) was lower than that in the placebo group (14.
9%)
.

The rate of renal composite events was 22% lower in the liraglutide group than in the placebo group, and the risk of macroalbuminuria was improved
.

 ② SCALE trial The SCALE trial included 846 overweight or obese diabetic patients who were randomly assigned to 3 mg, 1.
8 mg liraglutide or placebo
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When the 56-week study ended, patients in the liraglutide group lost significantly more weight compared to the placebo group
.

However, urinary protein-to-creatinine ratio (UACR) decreased in both liraglutide groups
.

 ③ The SUSTAIN series of trials The SUSTAIN series of trials included 10 randomized controlled trials designed to evaluate the effectiveness of semaglutide on glycemic control in patients with type 2 diabetes
.

Although patients' eGFR decreased slightly at the beginning of the trial (weeks 12-16), there was no statistical difference compared with other glucose-lowering drugs or placebo throughout the trial period
.

In addition, the UACR value of the semaglutide group showed a downward trend
.

Notably, in 3297 patients, the onset or worsening of renal disease (3.
8% vs 6.
1%) was superior to the placebo group, and there was a reduction in macroalbuminuria (up to 46%)
.

COVID-19 and GLP-1Ra As we all know, the damage caused by COVID-19 to the body is mainly due to the "cytokine storm", that is, the level of inflammatory factors rises significantly, which damages alveolar epithelial cells, causing hyaline degeneration and parenchymal damage to the lungs
.

GLP-1Ra can disrupt the inflammatory process, has a certain anti-inflammatory effect, and reduce systemic inflammatory biomarkers, which is particularly evident in people with type 2 diabetes and obesity
.

 Preclinical studies have shown that GLP-1Ra inhibits pro-inflammatory cytokines, stimulates the eNOS/sGC/PKG signaling pathway, and causes inactivation of the NF-kB signaling pathway
.

In addition, liraglutide reduces the expression of key inflammasomes
.

In short, GLP-1Ra is anti-inflammatory and may be effective against COVID-19
.

 Overall, GLP-1Ra reduces the risk of cardiovascular events, is renoprotective, and has a favorable safety profile
.

In addition, GLP-1Ra can be beneficial to new crown patients from the perspective of pharmacological effects
.

Perhaps, for new crown patients with diabetes or DKD, GLP-1Ra may be better than other hypoglycemic drugs
.

 References: 1.
Li Hongyuan, Zhu Jieyun, Zhong Zhimei, et al.
Meta-analysis of the prevalence of underlying diseases in patients with severe novel coronavirus pneumonia (COVID-19) [J].
Journal of Difficult and Difficult Diseases, 2020, 19(6): 72 .
Antonio G, Rosario M, Massimiliano A, et al.
GLP-1 RECEPTOR AGONISTS AND RENALOUTCOMES IN PATIENTS WITH DIABETES MELLITUS TYPE 2 AND DIABETIC KIDNEY DISEASE:STATE OF THE ART.
CKJ.
Mar 12, 2022.