Evaluation of the pharmacokinetics of metformin and acarbose in the common marmoset

Abstract

Metformin has beneficial effects on several age-related diseases (e.g., diabetes, obesity, cancer) and extends lifespan in nematodes and mice. Acarbose, an FDA-approved agent for treating type 2 diabetes, prevents breakdown of complex carbohydrates. Both compounds have been suggested as potential anti-aging interventions and acarbose has been shown to extend mouse longevity by the Intervention Testing Program (ITP). One potential next step is to assess the effect of these interventions on healthspan and lifespan in non-human primates. The common marmoset (Callithrix jacchus) is a small new world monkey with a relatively short life span and small size, both valuable for the translation potential of this nonhuman primate species for the study of aging and chronic disease. However, the dosing and assessment of potential side effects of either metformin or acarbose in this species have yet to be assessed. This study evaluated the pharmacokinetics of two dosage levels each of metformin or acarbose (given separately) in two small groups of young marmosets (n = 5/group) treated for 24 h to define the pharmacokinetics of each drug. The ability to rapidly and reliably dose socially housed marmosets with an oral form of acarbose or metformin that is well tolerated indicates that this species is a reliable model for testing acarbose and metformin in a safe and efficient way in a long-term intervention.

Risk Factors for Poor Outcomes of Diabetes Patients With COVID-19: A Single-Center, Retrospective Study in Early Outbreak in China

“…The investigation provided interesting information that α-GI could be an independent protector for clinical outcome in diabetic patients with COVID-19 infection. Moreover, the protecting effect is obvious even though only a small portion of α-glucosidase inhibitor is absorbed into circulation ( 19 ) Both the SARS-CoV-2 and the Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) use ACE2 for entry into host cells. Previous studies have found that the N-linked glycan structure of the ACE2 could be altered by glucosidase inhibitors ( 20 ).…”

“…Since late December 2019, a number of pneumonia cases caused by a novel coronavirus named Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has been reported in Wuhan, China. The resultant disease from SARS-CoV-2 infection is named as Coronavirus Disease of 2019 (COVID- 19) by the World Health Organization (WHO) (1). The COVID-19 pandemic has so far spread to all continents.…”

Rapamycin-induced hyperglycemia is associated with exacerbated age-related osteoarthritis

“…Twenty-five-milligram samples of diets enriched with Rap (14 ppm) or the combination of Rap+Met (14 + 1000 ppm), and aliquots of whole blood ( n = 4 per group) were sent to the Bioanalytical Pharmacology Core at the San Antonio Nathan Shock Center to confirm drug concentrations in the diet and in circulation. Analysis was performed using tandem HPLC-MS as described previously [ 14 , 47 , 48 ]. Frozen aliquots of plasma were thawed to measure glucose and lactate concentrations using the YSI Biochemistry Analyzer (YSI 2900).…”

In Vitro Evaluation of the Anti-Diabetic Potential of Aqueous Acetone Helichrysum petiolare Extract (AAHPE) with Molecular Docking Relevance in Diabetes Mellitus

“…In view of this, the drugs formulated using these bioactive compounds that fulfilled Lipinski’s rule of five may have some significant advantages over the synthetic compound (acarbose). Interestingly, acarbose violated three out of the five rules and has been reported to be metabolically unstable [ 53 , 54 ].…”