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

Abstract

In Covid-19, variations in fasting blood glucose are considered a distinct risk element for a bad prognosis and outcome in Covid-19 patients. Tirazepatide (TZT), a dual glucagon-like peptide-1 (GLP-1)and glucose-dependent insulinotropic polypeptide (GIP) receptor agonist may be effective in managing Covid-19-induced hyperglycemia in diabetic and non-diabetic patients. The beneficial effect of TZT in T2DM and obesity is related to direct activation of GIP and GLP-1 receptors with subsequent improvement of insulin sensitivity and reduction of body weight. TZT improves endothelial dysfunction (ED) and associated inflammatory changes through modulation of glucose homeostasis, insulin sensitivity, and pro-inflammatory biomarkers release. TZT, through activation of the GLP-1 receptor, may produce beneficial effects against Covid-19 severity since GLP-1 receptor agonists (GLP-1RAs) have anti-inflammatory and pulmoprotective implications in Covid-19. Therefore, GLP-1RAs could effectively treat severely affected Covid-19 diabetic and non-diabetic patients. Notably, using GLP-1RAs in T2DM patients prevents glucose variability, a common finding in Covid-19 patients. Therefore, GLP-1RAs like TZT could be a therapeutic strategy in T2DM patients with Covid-19 to prevent glucose variability-induced complications. In Covid-19, the inflammatory signaling pathways are highly activated, resulting in hyperinflammation. GLP-1RAs reduce inflammatory biomarkers like IL-6, CRP, and ferritin in Covid-19 patients. Therefore, GLP-1RAs like TZ may be effective in Covid-19 patients by reducing the inflammatory burden. The anti-obesogenic effect of TZT may reduce Covid-19 severity by ameliorating body weight and adiposity. Furthermore, Covid-19 may induce substantial alterations in gut microbiota. GLP-1RA preserves gut microbiota and prevents intestinal dysbiosis. Herein, TZT, like other GLP-1RA, may attenuate Covid-19-induced gut microbiota alterations and, by this mechanism, may mitigate intestinal inflammation and systemic complications in Covid-19 patients with either T2DM or obesity. As opposed to that, glucose-dependent insulinotropic polypeptide (GIP) was reduced in obese and T2DM patients. However, activation of GIP-1R by TZT in T2DM patients improves glucose homeostasis. Thus, TZT, through activation of both GIP and GLP-1, may reduce obesity-mediated inflammation. In Covid-19, GIP response to the meal is impaired, leading to postprandial hyperglycemia and abnormal glucose homeostasis. Therefore, using TZT in severely affected Covid-19 patients may prevent the development of glucose variability and hyperglycemia-induced oxidative stress. Moreover, exaggerated inflammatory disorders in Covid-19 due to the release of pro-inflammatory cytokines like IL-1β, IL-6, and TNF-α may lead to systemic inflammation and cytokine storm development. Besides, GIP-1 inhibits expression of IL-1β, IL-6, MCP-1, chemokines and TNF-α. Therefore, using GIP-1RA like TZT may inhibit the onset of inflammatory disorders in severely affected Covid-19 patients. In conclusion, TZT, through activation of GLP-1 and GIP receptors, may prevent SARS-CoV-2-induced hyperinflammation and glucose variability in diabetic and non-diabetic patients.

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

“…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.…”

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

“…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.…”