March 18, 2024 | News | Living with MS MS Research

Diabetes drugs may help prevent MS

A new study suggests that some diabetes drugs – including Ozempic – may help reduce the risk of developing MS. The study results were presented at the Americas Committee for Treatment and Research in MS (ACTRIMS) Forum, held February 29-March 2 in West Palm Beach, Florida.

Obesity during childhood and adolescence has been shown to increase the risk of developing MS (Harroud and colleagues. Mult Scler 2021;27:1994-2000). The reasons behind this MS-obesity connection are not well understood. Some researchers have suggested that fat tissue produces substances (called adipokines) that promote a generalized inflammation throughout the body (Correale and Marrodan. Front Immunol 2022;13:1038393). Others point to the fact that obesity lowers levels of vitamin D (another MS risk factor) (Harroud 2021). The problem may be diet, which can enrich populations of microbes in the gastrointestinal tract that promote inflammation (Samara and colleagues. Mult Scler Relat Disord 2023;76:104768). In addition, a recent genetics study found that MS and obesity share a number of genes so people who have a genetic risk of developing obesity also have a higher risk of MS (Zeng and colleagues. EBioMedicine 2023;93:104647). All of these theories are being investigated.

However, the link between MS and obesity raises the question of whether drugs that induce weight loss might be beneficial in MS. For example, animal studies have suggested that metformin (Glucophage), which lowers blood sugar in people with diabetes and causes some weight loss, may be beneficial in MS.

Perhaps the most high-profile weight-loss drug at the moment is Ozempic (semaglutide), which was developed to treat Type 2 diabetes. An oral formulation (Rybelsus) has also obtained FDA approval for diabetes. Semaglutide is effective in diabetes because it stimulates insulin release by cells, a process that is impaired in diabetes. Weight loss was a side effect (or benefit) seen in clinical trials, so semaglutide was subsequently repackaged as a weight-loss drug (with the brand name Wegovy). The theory is that in addition to having effects on insulin, this class of drugs (called GLP-1 agonists) also acts in the brain to regulate appetite and caloric intake.

Semaglutide has proved popular – Ozempic sales in the U.S. in 2023 were about $9 billion, $4 billion for Wegovy and another $2 billion for Rybelsus. Other drugs in this class are tirzepatide (Mounjaro for diabetes, Zepbound for weight loss), dulaglutide (sold as Trulicity), and liraglutide (Saxenda). Another diabetes drug that causes weight loss is empagliflozin (Jardiance), which works by a different mechanism. Ozempic, Jardiance and Trulicity were the top 3 best-selling diabetes drugs in the U.S. last year (with some of that use for weight loss rather than diabetes). All of these products are in short supply because of the high demand – not least because of endorsements by celebrities, who use these products for cosmetic purposes.

A new study used the Food and Drug Administration’s adverse effects database over a 20-year period to see if there was an association between weight-loss drugs and MS (Shirani and colleagues. ACTRIMS Forum 2024;P178). The database found that MS-related side effects were less common in people taking weight loss-inducing diabetes drugs, including Glucophage, Ozempic/Wegovy, Saxenda, Trulicity and Jardiance. However, this effect did not appear to be related to weight loss itself. Other drugs that cause weight loss (such as amphetamine) were not associated with fewer MS-related events.

This study poses a number of problems. An adverse events database is likely too blunt a tool to identify an association between a class of drugs and MS risk. And most of the weight-loss-inducing drugs linked to a lower MS risk have only been on the market for a brief period, so that may skew the results.

The study does seem to suggest that weight loss in itself would be unlikely to prevent the development of MS since other drugs causing weight loss were not linked to MS. This underscores the point that obesity is a risk factor for MS, not a cause.

The study does raise the intriguing possibility that some diabetes drugs may have effects in the brain that may be beneficial in people with MS. Animal studies have suggested that drugs such as metformin and semaglutide may protect the brain against tissue damage (DellaValle and colleagues. Front Pharmacol 2016:7:433), although the way this might occur has not been worked out. Thus far, only one study, which used metformin as an add-on to Rebif, failed to show a benefit in people with MS (Abdelgaied and colleagues. J Neurol 2024;271:1124-1132). It remains to be seen if the new generation of diabetes drugs is more successful in reducing the risk or severity of MS.

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