The field of weight loss medications has recently become much more exciting as trials have shown some of the new kids on the block to promote nearly 20% weight loss.  These are numbers far beyond what can be achieved with prior medications.  Leading these headlines is the medication semaglutide, branded in different formulations as Wegovy, Rybelsus, and Ozempic, and related to prior medications like liraglutide, exenatide, dulaglutide, and lixisenatide which had demonstrated weight loss, albeit less substantial than semaglutide.

The future also looks bright as medications with similar mechanisms plus "bonus" effects are demonstrating potentially greater weight loss with fewer side effects due to the synergy between receptor targets of the medication.  New formulations are also combining semaglutide with other medications for greater effect in treating diabetes and weight loss.

When looking at the data from prior trials, however, researchers noticed additional benefits being demonstrated.  Specifically, in addition to their effect in controlling diabetes, this class of medication was found to reduce cardiovascular disease (heart attacks and heart failure), strokes, and all causes of death overall.  In fact, the benefits spanned multiple body systems beyond the brain and heart as patients treated also had protection against worsening kidney disease (common in patients with diabetes).

Given the higher rate of cognitive decline and dementia in patients with diabetes, there is been additional interest in any potential neuroprotective effect of this class of medication and prevention of cognitive decline.  Mouse studies in which the receptor target of this class of medications demonstrated that without the effect of the hormone, mice demonstrated learning deficits/cognitive impairment.  On top of this, other studies have shown that liraglutide specifically improves memory and learning, reduces proteins associated with Alzheimer's disease, and increases the number of neurons in the hippocampus-an area crucial for memory that is affected early in Alzheimer's disease.  In reviewing the cognitive assessments of patients on dulaglutide, researchers noted a 14% reduction in substantive cognitive impairment.  As a result investigators pulled the data from multiple randomized control trials of different GLP-1 medications to better assess if there is any difference in the rate reported of individual developing dementia who had received the study medication.  As suspected, patient is in the study had a 53% lower risk of developing dementia relative to those receiving placebo.

An important consideration is whether or not these improvements were simply due to better control of diabetes, given the effect diabetes has on promoting dementia.  The study compared this class of medication with other treatments for diabetes and found negligible/no statistical benefits in insulin, sulfonylureas, DPP 4 inhibitors, or meglitinides in reducing the risk of developing dementia.  This implies that the benefit must be through other mechanisms beyond better blood sugar control, which was suggested by the earlier-mentioned mouse studies. As other studies have indicated a potential anti-inflammatory effect of these medications, some component of the benefit is likely due to a reduced level of inflammation in the brain that has been associated with dementia and other neurodegenerative diseases like Parkinson's disease.