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Med Hypotheses ; 171: 111020, 2023 Feb.
Article in English | MEDLINE | ID: covidwho-2211144


Research evidence suggests that adipocytes in obesity might facilitate SARS-CoV-2 replication, for it was only found in adipose tissue of individuals with overweight or obesity but not lean individuals who died from COVID-19. As lipid metabolism is key to adipocyte function, and viruses are capable of exploiting and manipulating lipid metabolism of host cells for their own benefit of infection, we hypothesize that adipocytes could not only impair host immune defense against viral infection, but also facilitate SARS-CoV-2 entry, replication and assembly as a reservoir to boost the viral infection in obesity. The latter of which could mainly be mediated by SARS-CoV-2 hijacking the abnormal lipid metabolism in the adipocytes. If these were to be confirmed, an approach to combat COVID-19 in people with obesity by taking advantage of the abnormal lipid metabolism in adipocytes might be considered, as well as modifying lipid metabolism of other host cells as a potential adjunctive treatment for COVID-19.

Diabetes Ther ; 13(5): 847-872, 2022 May.
Article in English | MEDLINE | ID: covidwho-1750861


Over recent years, the expanding evidence base for sodium-glucose cotransporter-2 inhibitor (SGLT2i) therapies has revealed benefits beyond their glucose-lowering efficacy in the treatment of Type 2 diabetes mellitus (T2DM), resulting in their recognition as cardiorenal medicines. While SGLT2is continue to be recommended among the second-line therapies for the treatment of hyperglycaemia, their true value now extends to the prevention of debilitating and costly cardiovascular and renal events for high-risk individuals, with particular benefit shown in reducing major adverse cardiac events and heart failure (HF) and slowing the progression of chronic kidney disease. However, SGLT2i usage is still suboptimal among groups considered to be at greatest risk of cardiorenal complications. The ongoing coronavirus disease 2019 (COVID-19) pandemic has intensified financial pressures on healthcare systems, which may hamper further investment in newer effective medicines. Emerging evidence indicates that glycaemic control should be prioritised for people with T2DM in the era of COVID-19 and practical advice on the use of T2DM medications during periods of acute illness remains important, particularly for healthcare professionals working in primary care who face multiple competing priorities. This article provides the latest update from the Improving Diabetes Steering Committee, including perspectives on the value of SGLT2is as cost-effective therapies within the T2DM treatment paradigm, with particular focus on the latest published evidence relating to the prevention or slowing of cardiorenal complications. The implications for ongoing and future approaches to diabetes care are considered in the light of the continuing coronavirus pandemic, and relevant aspects of international treatment guidelines are highlighted with practical advice on the appropriate use of SGLT2is in commonly occurring T2DM clinical scenarios. The 'SGLT2i Prescribing Tool for T2DM Management', previously published by the Steering Committee, has been updated to reflect the latest evidence and is provided in the Supplementary Materials to help support clinicians delivering T2DM care.

N Engl J Med ; 384(11): 989-1002, 2021 03 18.
Article in English | MEDLINE | ID: covidwho-1139778


BACKGROUND: Obesity is a global health challenge with few pharmacologic options. Whether adults with obesity can achieve weight loss with once-weekly semaglutide at a dose of 2.4 mg as an adjunct to lifestyle intervention has not been confirmed. METHODS: In this double-blind trial, we enrolled 1961 adults with a body-mass index (the weight in kilograms divided by the square of the height in meters) of 30 or greater (≥27 in persons with ≥1 weight-related coexisting condition), who did not have diabetes, and randomly assigned them, in a 2:1 ratio, to 68 weeks of treatment with once-weekly subcutaneous semaglutide (at a dose of 2.4 mg) or placebo, plus lifestyle intervention. The coprimary end points were the percentage change in body weight and weight reduction of at least 5%. The primary estimand (a precise description of the treatment effect reflecting the objective of the clinical trial) assessed effects regardless of treatment discontinuation or rescue interventions. RESULTS: The mean change in body weight from baseline to week 68 was -14.9% in the semaglutide group as compared with -2.4% with placebo, for an estimated treatment difference of -12.4 percentage points (95% confidence interval [CI], -13.4 to -11.5; P<0.001). More participants in the semaglutide group than in the placebo group achieved weight reductions of 5% or more (1047 participants [86.4%] vs. 182 [31.5%]), 10% or more (838 [69.1%] vs. 69 [12.0%]), and 15% or more (612 [50.5%] vs. 28 [4.9%]) at week 68 (P<0.001 for all three comparisons of odds). The change in body weight from baseline to week 68 was -15.3 kg in the semaglutide group as compared with -2.6 kg in the placebo group (estimated treatment difference, -12.7 kg; 95% CI, -13.7 to -11.7). Participants who received semaglutide had a greater improvement with respect to cardiometabolic risk factors and a greater increase in participant-reported physical functioning from baseline than those who received placebo. Nausea and diarrhea were the most common adverse events with semaglutide; they were typically transient and mild-to-moderate in severity and subsided with time. More participants in the semaglutide group than in the placebo group discontinued treatment owing to gastrointestinal events (59 [4.5%] vs. 5 [0.8%]). CONCLUSIONS: In participants with overweight or obesity, 2.4 mg of semaglutide once weekly plus lifestyle intervention was associated with sustained, clinically relevant reduction in body weight. (Funded by Novo Nordisk; STEP 1 number, NCT03548935).

Anti-Obesity Agents/administration & dosage , Glucagon-Like Peptide 1/agonists , Glucagon-Like Peptides/administration & dosage , Obesity/drug therapy , Adult , Anti-Obesity Agents/adverse effects , Body Composition/drug effects , Body Mass Index , Cholelithiasis/chemically induced , Diarrhea/chemically induced , Double-Blind Method , Female , Glucagon-Like Peptides/adverse effects , Healthy Lifestyle , Humans , Injections, Subcutaneous , Lipids/blood , Male , Middle Aged , Nausea/chemically induced , Obesity/complications , Prediabetic State/complications , Weight Loss/drug effects