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The occurrence of obesity is an increasing issue worldwide, especially in industrialized countries. Weight loss is important both to treat obesity and to prevent the development of complications. Currently, several drugs are used to treat obesity, but their efficacy is modest. Thus, new anti-obesity treatments are needed. Recently, there has been increased interest in the development of incretins that combine body-weight-lowering and glucose-lowering effects. Therefore, a new drug that simultaneously coactivates both the glucose-dependent insulinotropic polypeptide (GIP) receptor (GIPR) and the glucagon-like peptide-1 receptor (GLP-1R) has been developed. Tirzepatide, the first in this class, improves glycemic control by increasing insulin sensitivity and lipid metabolism as well as by reducing body weight. Combining the activation of the two receptors, greater improvement of β-cell function offers more effective treatment of diabetes and obesity with fewer adverse effects than selective GLP-1R agonists. In the present review, we discuss the progress in the use of GIPR and GLP-1R coagonists and review literature from in vitro studies, animal studies, and human trials, highlighting the synergistic mechanisms of tirzepatide.

Since December 2019, a new coronavirus, called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread around the world, causing the coronavirus 2019 (COVID-19) pandemic. From the beginning, SARS-CoV-2 has put a strain on the health system. In fact, many patients have had severe forms of the disease with the need for hospitalization due to respiratory failure. To contain the pandemic, the most widely used approach has been lockdowns. Social restrictions have been reduced thanks to the development of vaccines and targeted therapies. However, fatal events still occur among people at high risk of serious infection, such as patients with concomitant diabetes. Different mechanisms have been proposed to explain the poor prognosis of patients with diabetes and COVID-19, but the specific cause is unclear. It is now known that insulin resistance, inflammation, and cytokine storm are involved. Moreover, SARS-CoV-2 uses the angiotensin-converting enzyme 2 receptors to enter cells. This receptor is expressed on pancreatic beta cells and, during infection, it appears that receptor involvement may induce hyperglycemia in patients with or without diabetes. In this study, we discuss the mechanisms underlying the poor prognosis in people with COVID-19 and diabetes and what may improve the outcome in these patients.

BackgroundThe effects of sacubitril/valsartan (sac/val) on metabolic parameters and insulin resistance (IR) in non-obese/prediabetic patients have not been previously described.AimTo evaluate the effects of sac/val on glycemic and metabolic parameters, Homeostatic Model Assessment of IR (HOMA-IR), and echocardiographic parameters in prediabetic patients with heart failure with reduced ejection fraction (HFrEF).MethodsFifty-nine patients with HFrEF (EF < 35%) but without obesity and/or type 2 diabetes mellitus have been enrolled. All the patients at baseline and week 24 underwent complete anthropometrical evaluation and were subjected to an echocardiogram test. IR has been assessed by HOMA-IR.ResultsAfter 24-week of treatment with sac/val, a significant reduction in fasting plasma glucose (109 ± 9 vs 103 ± 8 mg/dl, p < 0.0001), fasting plasma insulin (16 ± 4 vs 10 ± 4 UI/L), and hemoglobin A1c (HbA1c) value (6% ± 0.5% vs 5.3% ± 0.3%, p < 0.0001) was observed. Similarly, we observed a significant improvement in IR (HOMA-IR, 4.4 ± 0.9 vs 2.5 ± 0.6, p < 0.0001). The echocardiogram evaluation showed a significant reduction of the left ventricular end-diastolic volume (168 ± 24 vs 158 ± 22 ml, p < 0.05), a significant reduction of the left ventricular end-systolic volume (111 ± 26 vs 98 ± 22 ml, p < 0.005), and a significant reduction of E/e′ ratio. Sac/val use was also associated with an average 5.1% increase in ejection fraction.ConclusionsOur data seem to indicate that sal/val enhances metabolic control and improves insulin resistance also in prediabetic non-obese patients with HFrEF.