Potential role of tirzepatide towards Covid-19 infection in diabetic patients: a perspective approach

Batiha, Gaber El‐Saber; Al-Kuraishy, Hayder M; Al-Gareeb, Ali I; Ashour, Nada A.; Negm, Walaa A.

doi:10.1007/s10787-023-01239-4

Cited by 6 publications

(2 citation statements)

References 87 publications

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“…It has been shown that GLP-1 and long-acting GLP-1 analogues are not only degraded by DPP4 but also by NEP. 82,83 NEP inhibition by specific inhibitors augments circulating GLP-1, which has a neuroprotective effect against Aβ-induced cytotoxicity, neuroinflammation, synaptic dysfunction-induced memory and cognitive dysfunctions. 82 Long 84 -acting GLP-1 analogues are highly resistant to the effect of DPP4.…”

Section: Nep Inhibitors and Glp-1mentioning

confidence: 99%

Neprilysin inhibitors and risk of Alzheimer's disease: A future perspective

Ali,

Al‐Kuraishy,

Al‐Gareeb

et al. 2023

J Cellular Molecular Medi

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Alzheimer's disease (AD) is a heterogeneous neurodegenerative disease with multifaceted neuropathological disorders. AD is characterized by intracellular accumulation of phosphorylated tau proteins and extracellular deposition of amyloid beta (Aβ). Various protease enzymes, including neprilysin (NEP), are concerned with the degradation and clearance of Aβ. Indeed, a defective neuronal clearance pathway due to the dysfunction of degradation enzymes might be a possible mechanism for the accumulation of Aβ and subsequent progression of AD neuropathology. NEP is one of the most imperative metalloproteinase enzymes involved in the clearance of Aβ. This review aimed to highlight the possible role of NEP inhibitors in AD. The combination of sacubitril and valsartan which is called angiotensin receptor blocker and NEP inhibitor (ARNI) may produce beneficial and deleterious effects on AD neuropathology. NEP inhibitors might increase the risk of AD by the inhibition of Aβ clearance, and increase brain bradykinin (BK) and natriuretic peptides (NPs), which augment the pathogenesis of AD. These verdicts come from animal model studies, though they may not be applied to humans. However, clinical studies revealed promising safety findings regarding the use of ARNI. Moreover, NEP inhibition increases various neuroprotective peptides involved in inflammation, glucose homeostasis and nerve conduction. Also, NEP inhibitors may inhibit dipeptidyl peptidase 4 (DPP4) expression, ameliorating insulin and glucagon‐like peptide 1 (GLP‐1) levels. These findings proposed that NEP inhibitors may have a protective effect against AD development by increasing GLP‐1, neuropeptide Y (NPY) and substance P, and deleterious effects by increasing brain BK. Preclinical and clinical studies are recommended in this regard.

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Section: Nep Inhibitors and Glp-1mentioning

confidence: 99%

Neprilysin inhibitors and risk of Alzheimer's disease: A future perspective

Ali,

Al‐Kuraishy,

Al‐Gareeb

et al. 2023

J Cellular Molecular Medi

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“…Tirzepatide gastrointestinal adverse reactions mainly included nausea, vomiting, diarrhea, and decreased appetite, but the severity of these symptoms was mostly mild or moderate and the duration is relatively short. These effects are usually observed in irritable bowel syndrome and may suggest a potential effect of tirzepatide on the gut microbiota ( 40 ). The risk of hypoglycemia is significantly lower in the insulin group, slightly higher to the GLP-1 RA and placebo groups but without statistically significant differences.…”

Section: Discussionmentioning

confidence: 99%

Tirzepatide as a novel effective and safe strategy for treating obesity: a systematic review and meta-analysis of randomized controlled trials

Cai,

Zhang,

Yao

et al. 2024

Front. Public Health

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ObjectiveTo systematically evaluate the efficacy and safety of a new hypoglycemic drug, tirzepatide, for treating obesity based on indicators such as BMI, waist circumference, and body weight.MethodsA search formula was written using search terms such as “tirzepatide,” “overweight,” and “obesity.” A comprehensive search was conducted on databases such as PubMed, Cochrane Library, Embase, and Web of Science using a computer. Random controlled trial (RCT) literature was selected based on inclusion and exclusion criteria. After extracting the data, literature bias risk assessment and meta-analysis were conducted using RevMan 5.4 software. The search deadline is from the establishment of each database to May 2023.ResultsA total of 12 randomized controlled trials were included, with a total of 11,758 patients. Meta analysis results showed that compared with the glucagon like peptide-1 receptor agonist (GLP-1 RAs), placebo and insulin groups, tirzepatide could significantly reduce the BMI (body mass index) of patients [MD = −1.71, 95% CI (−2.46, −0.95), p < 0.00001], [MD = −3.99, 95% CI (−3.69, −2.45), p < 0.00001], [MD = −4.02, 95% CI (−4.72, −3.31), p < 00.00001]. In terms of decreasing waist circumference, tirzepatide has a more significant advantage [MD = −4.08, 95% CI (−5.77, −2.39), p < 0.00001], [MD = −7.71, 95% CI (−10.17, −5.25), p < 0.00001], [MD = −9.15, 95% CI (−10.02, −8.29), p < 0.00001]. In the analysis of body weight, tirzepatide showed a more significant reduction effect compared to the control group [MD = −5.65, 95% CI (−7.47, −3.82), p < 0.001], [MD = −10.06, 95% CI (−12.86, −7.25), p < 0.001], [MD = −10.63, 95% CI (−12.42, −8.84), p < 0.001]. In comparison with placebo, tirzepatide had a prominent advantage in weight loss ≥20% and ≥25% [RR = 30.43, 95% CI (19.56, 47.33), p < 0.00001], [RR = 37.25, 95% CI (26.03, 53.30), p < 0.00001]. Subgroup analysis showed a dose-dependent therapeutic effect. In terms of safety, compared with the placebo and insulin groups, the incidence of gastrointestinal adverse reactions was markedly higher in the tirzepatide group, slightly higher to the GLP-1 RAs group. The hypoglycemic (<70 mg/dL) risk of tirzepatide was slightly higher to that of placebo and GLP-1 RAs, but significantly lower than that of the insulin group [RR = 0.46, 95% CI (0.36, 0.58), p < 0.001]. The incidence of other adverse events, including pancreatitis, cholecystitis, major adverse cardiovascular events-4, hypersensitivity reactions, and neoplasms did not show significant statistical differences compared to the control group (p > 0.05).ConclusionTirzepatide, as a weight loss drug, significantly reduces BMI, waist circumference and body weight while gastrointestinal adverse reactions need to be vigilant. Overall, its efficacy is significant and its safety is high.

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SARS-CoV-2 infection and dysregulation of nuclear factor erythroid-2-related factor 2 (Nrf2) pathway

Hamad,

Al-kuraishy,

Alexiou

et al. 2023

Cell Stress and Chaperones

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Coronavirus disease 2019 (COVID-19) is a recent pandemic caused by a novel severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) leading to pulmonary and extra-pulmonary manifestations due to the development of oxidative stress (OS) and hyperinflammation. The underlying cause for OS and hyperinflammation in COVID-19 may be related to the inhibition of nuclear factor erythroid 2-related factor 2 (Nrf2), a master regulator of antioxidative responses and cellular homeostasis. The Nrf2 pathway inhibits the expression of pro-inflammatory cytokines and the development of cytokine storm and OS in COVID-19. Nrf2 activators can attenuate endothelial dysfunction (ED), renin-angiotensin system (RAS) dysregulation, immune thrombosis, and coagulopathy. Hence, this review aimed to reveal the potential role of the Nrf2 pathway and its activators in the management of COVID-19. As well, we tried to revise the mechanistic role of the Nrf2 pathway in COVID-19.

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Potential role of tirzepatide towards Covid-19 infection in diabetic patients: a perspective approach

Cited by 6 publications

References 87 publications

Neprilysin inhibitors and risk of Alzheimer's disease: A future perspective

Neprilysin inhibitors and risk of Alzheimer's disease: A future perspective

Tirzepatide as a novel effective and safe strategy for treating obesity: a systematic review and meta-analysis of randomized controlled trials

SARS-CoV-2 infection and dysregulation of nuclear factor erythroid-2-related factor 2 (Nrf2) pathway

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