The field of diabetes care is undergoing what in hindsight might appear to be a ‘Banting and Best’ like historical moment. The discovery of the Glucagon-Like Peptide-1 Receptor Agonists (GLP-1RA) and the study of their benefits across organs has been full of unexpected surprises. The results of the advancement in the field of incretin-based therapies were on display in full swing at the American Diabetes Association (ADA) Scientific Sessions 2024 in Orlando, Florida.
Until now, incretin-based therapies have shown improvement in body weight, glycemic control, major adverse cardiovascular events, and composite major kidney disease events. The results of the SURMOUNT-OSA trial, showcased at the ADA Scientific Sessions 2024, showed that tirzepatide was superior to placebo in reducing the mean apnea-hypopnea index (AHI) in people with moderate to severe obstructive sleep apnea (OSA) with or without the use of positive airway pressure (PAP) therapy. The study also showed improvement in the hypoxic burden as well as participant reported outcomes. The results confirmed the results of a previous meta-analysis which showed that a 20% reduction in body mass index (BMI) correlated with a >50% reduction in AHI. GLP-1RA are known to have pleiotropic effects on various organs in the body and further sub-analysis might throw some hypotheses generating light on the effects of GLP-1RA in the respiratory system.
The SELECT study which evaluated semaglutide versus placebo for cardiovascular outcomes in people with obesity and established cardiovascular disease without type 2 diabetes has been previously published and showed a significant reduction in major adverse cardiovascular events in participants treated with semaglutide 2.4 mg. Additional data presented at the ADA Scientific Sessions 2024 showed that the reduction in major adverse cardiovascular events was seen across the spectrum of body weight loss and glycemic changes. The results were applicable in participants who lost minimal weight or had minimal to no improvement in their glycemic control, which indicates that the benefit of semaglutide was independent of the weight loss or glycemic control and directs us to think towards the pleiotropic effects of GLP-1RA on the heart.
The FLOW study which evaluated semaglutide versus placebo for kidney disease outcomes in people with chronic kidney disease and type 2 diabetes has been previously published and showed a reduction in a composite outcome of onset of kidney failure, sustained 50% or greater reduction in eGFR from baseline, or death from kidney-related or cardiovascular causes in those treated with semaglutide. Further data was presented at the ADA Scientific Sessions 2024 showing that the use of sodium glucose cotransporter-2 inhibitors (SGLT-2i) at baseline had no effect on the primary outcome of the trial with power being limited due to the minimal use of SGLT2i at trial entry.
With more and more data on GLP-1RA benefits on various organs of the body, the evidence upon us points strongly towards the interconnectedness of various highly prevalent chronic diseases. Despite overwhelming evidence of benefit, the design of the current healthcare delivery models show poor uptake of guideline directed medical therapy to treat individuals with type 2 diabetes and atherosclerotic cardiovascular disease. Asynchronous healthcare delivery models can slow the rapid rollout of guideline recommendations suggesting that it could take longer than a decade and a half for such knowledge to be implemented. The need of the hour is to realize the interconnectedness of chronic disease states to develop a streamlined ‘one-stop-shop’ management approach that does not necessitate our patients having to deal with a sub-specialty fragmented healthcare system. This is imperative in the light of the knowledge that GLP-1RA can reduce mortality. Who could have imagined that a class of medication would bring together sub-specialists!
Dr. Agarwal has no conflicts of interest to report.
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