Reclaiming Ozempic: the use of semaglutide to protect kidney function

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Content warning: discussions of weight loss/eating disorders. 

Semaglutide, which is one of the active ingredients in brand name drugs Ozempic and Wegovy, has caused a frenzy in the world of weight loss as a supposed ‘miracle drug’. Celebrity advocates have ranged from Elon Musk to Oprah Winfrey with Sharon Osbourne televising the aggressive results of treatment on Celebrity Big Brother. In fact, the use of GLP-1 agonists, of which semaglutide is a variant, has become so popular that in May 2024 health pollster KFF estimated that 1 in 8 have taken this class of drugs in their lives.

Despite the main publicity deriving from shocking weight loss results, semaglutide is licenced in the UK to treat two specific conditions. It was firstly approved as a drug to treat type two diabetes drug, tightly regulating blood sugar levels. One of the more useful side effects was weight loss, the use for which has been authorised by the National Institute for Health and Care Excellence (NICE), a body which issues guidance for the NHS, under strict criteria. Only doctors specialising in weight loss may issue an NHS prescription for individuals with a body mass index (BMI) of over 30 or over 27 if there are weight related medical conditions such as diabetes or high blood pressure. 

However, this does not prevent private doctors dishing out private prescriptions for the drug without following NICE’s guidance. Therefore, some people have acquired the drug ‘off-label’, where there is not a strong clinical need.

As these supposed ‘quick-fixes’ to lose weight get increasingly popular and increasingly misused, more harmful side effects have been demonstrated including reports of interference with contraceptive pills causing the ‘miracle drug’ to produce ‘miracle babies’, severe nausea and the distinct ‘Ozempic face’ popularised on social media. On a meta level, the off-label demand has diminished supplies for those who need it to manage their conditions.

Weekly injections showed benefits in several metrics for kidney function

A recent three-and-a-half-year clinical trial, known as SELECT, however, has revealed another, more positive outcome of semaglutide usage. This outcome is a result of the active ingredient, semaglutide, in protecting kidney function. Weekly injections showed benefits in several metrics for kidney function compared to those not receiving weekly injections including less adverse kidney-related events, a lower decline in glomerular filtration rate and a significant reduction in urinary albumin-to-creatine ratio. 

So, what is semaglutide? How does it aid kidney function? And, lastly, how will this study impact discussions around off-label weight-loss drug usage? 

GCSE Biology has versed us well in insulin, its adversary glucagon, and the use of insulin to treat type 1 diabetes. However, it does not cover the medication semaglutide and a lesser discussed hormone called GLP-1.

GLP-1 increases insulin secretion and inhibits glucagon secretion which reduces blood sugar levels. It does this by binding to a specific receptor in pancreas cell membranes. Furthermore, it has a role in the complex gut-brain hunger relationship, prolonging gut emptying time. With structural compatibility between a molecule and its receptor key to functionality, one way of replicating these blood-sugar-lowering and satiating effects, is by replicating the structure of GLP-1. 

This is where semaglutide comes into play. Semaglutide is in some ways a more optimised form of GLP-1, retaining structural similarity with additional modifications to increase the time it circulates in the bloodstream. This improves blood glucose level control, decreasing the likelihood of diabetes associated complications such as nerve damage and cardiovascular disease. It also emulates the same appetite-supressing effects of GLP-1, hence the utilisation for weight loss.

According to the journal Nature, researchers say that how semaglutide works is unclear. It could be from reductions in blood sugar linked kidney inflammation. Further research is required into underlying mechanisms of action and who should be eligible for the treatment, but scientists are confident in its potential for reducing risks of kidney disease. In an alternate study, a semaglutide manufacturer based in Denmark, Novo Nordsik, went as far as halting a clinical trial investigating the role of semaglutide in kidney disease because the results were overwhelming positive to the point that it was deemed unethical to continue giving patients a placebo (non-active control).

This evidence confirms the need to leave semaglutide as a transformative drug for those who have a medical necessity. In line with general discussions about media driven popularisations, we need better information and regulation to help people in making informed decisions. With the rather paradoxical rise in both eating disorders and obesity, this is more important than ever in the case of semaglutide. A weight loss drug grey area is growing and the ‘off label’ taking of drugs sets a scary precedent extending far beyond shedding a few pounds.

Image: Kawinnat Sue-ob via Wikimedia Commons

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