NEPCRN Journal Club
Journal Club topics are selected by members who have a particular interest, or a paper they want to discuss, and the aim is to enhance our critical analytical abilities in evaluating the medical evidence base.
We meet in the evening, either on a Wednesday or Thursday, every 1-2 months, and there is the option to join by zoom, although an in-person group meets at the Armidale Tablelands Clinical School building. If you would like to be invited to our next Journal Club, please join us as a member – it’s free!
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Semaglutide for weight-loss?
The evidence seems compelling for using semaglutide for weight loss in overweight or obese people with CVD risk but no diabetes, although we need to be wary of the biases in the studies due to the conflicts of interest in the authors who all received funding from the drug manufacturers.
Compliance with the medication will likely help patients lose over 10% of their bodyweight, but there is usually a bounce-back weight gain once they stop taking it – Garvey et al., (2022) Two-year effects of semaglutide in adults with overweight or obesity: the STEP 5 trial. Also, we don’t have very long term data, yet – only 4 years, so the long-term risks are unknown.
On the downside, it’s a costly non-PBS item at the moment ($460/month for the 2.4 mg dose), and the gastro-intestinal effects may be unbearable.
The RACGP news article on Wegovy from 2 August 2024 recommends that GPs discuss access, cost, expectations about weight loss, and the likely need for life-long medication use with their patients before commencing them on Wegovy.
Metformin, healthspan extension & longevity?
Targets of metformin among the hallmarks of aging. Metformin attenuates aging and aging-related diseases by targeting nine hallmarks of aging, including (1) four primary hallmarks (loss of proteostasis, telomere attrition, genomic instability and epigenetic alterations); (2) three antagonistic hallmarks (deregulated nutrient sensing, mitochondrial dysfunction, and cellular senescence); (3) two integrative hallmarks (altered intercellular communication and stem cell exhaustion). Chen S, Gan D, Lin S, Zhong Y, Chen M, Zou X, Shao Z, Xiao G. Metformin in aging and aging-related diseases: clinical applications and relevant mechanisms. Theranostics. 2022 Mar 6;12(6):2722-2740. doi: 10.7150/thno.71360. https://pmc.ncbi.nlm.nih.gov/articles/PMC8965502
In the August 2024 Journal Club, we reviewed an article titled Metformin in aging and aging-related diseases: clinical applications and relevant mechanisms
looking at the pre-clinical research suggesting that metformin might have usefulness as a healthy life-prolongation medication. Although metformin is largely used to treat diabetes, it may also offer protection in other age-related diseases, such as degenerative skeletal diseases, cardiovascular disease, dementia, obesity, fatty liver disease and polycystic ovarian syndrome.
We agreed with the authors’ conclusion that “multicenter, large-scale, double-blind, randomized, placebo-controlled trials are required to further elucidate the effects of metformin on aging and major aging-related diseases” not just type 2 diabetes.
Benefits and Harms of Diabetes (T2) drugs
In June 2024, we looked at a meta-analysis comparing risks and benefits of various diabetes medications Benefits and harms of drug treatment for type 2 diabetes: systematic review and network meta-analysis of randomised controlled trials
The table below is copied from the article. The green cells show benefit, the orange cells show harm, and the grey cells are no better than standard treatment. Standard treatments included standard care (i.e., lifestyle modification) and standard drug treatments (e.g., metformin and/or sulfonylureas) other than the drug of interest in the randomised trial.