Weight Loss and Diabetes Drugs: What’s the Latest Research?
What do we know about glucagon-like peptide-1 receptor agonists, and what does the latest research say?

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Drugs like Ozempic® and Mounjaro® have become blockbuster drugs as of late, making headlines not only for their powerful weight loss effects, but also for their potential to help other conditions – as well as their possible side effects.
These drugs target a receptor located on the outside of cells, called the glucagon-like peptide 1 receptor (GLP-1R). They work by mimicking the hormone GLP-1, which binds to these receptors and helps to control levels of insulin and glucose in the blood. Acting as GLP-1R agonists (GLP-1RAs), the drugs promote feelings of satiety and fullness, aiding weight loss among patients who are overweight or obese.
The huge waves being made by these drugs in the pharmaceutical industry cannot be denied; pharma brands Eli Lilly and Novo Nordisk have seen their value grow by over 50% this year, largely thanks to their offerings tirzepatide (also known as Mounjaro or Zepbound™) and semaglutide (Ozempic or Wegovy®).
GLP-1RAs were first approved by the US Food and Drug Administration (FDA) for type 2 diabetes in 2005 and for weight management in 2014; but a huge uptick in recent demand has had a profound impact, creating drug shortages, accessibility issues and the worrying appearance of falsified medicines.
Aside from their success for type 2 diabetes and overweight/obesity, numerous clinical studies have suggested that the drugs may also show promise for a host of other conditions, from alcohol use disorder to Parkinson’s. But in the wake of these promising results, reports of unpleasant side effects including stomach paralysis and suicidal ideation have prompted further studies and investigations.
So, what do we know about these drugs, and what is the latest research?
Success for weight loss
GLP-1RAs have shown considerable effects for weight loss to treat obesity. A recent Phase 3 trial published in Nature Medicine found that tirzepatide led to additional weight loss of over 20% when used alongside intensive lifestyle interventions in overweight or obese adults.
In the study – which was sponsored by drugmaker Eli Lilly – over 800 participants underwent 12 weeks of intensive lifestyle intervention to lose at least 5% of their body weight. They were then randomized into two groups that would receive either ascending doses of tirzepatide or a placebo once a week for 72 weeks.
The 12 weeks of lifestyle interventions led to an average reduction of 6.9% of the participants’ body weight. Those who went on to receive tirzepatide after this initial phase achieved an additional 21.1% weight loss in the following 72 weeks, bringing their total to an average of 26.6%. The placebo group, on the other hand, achieved a total weight loss of 3.8% on average. This translates to a total mean weight loss of 9 lbs (4.1 kg) for those taking a placebo, compared to the tirzepatide group’s 64.4 lbs (29.2 kg).
So, we know that the data shows a strong effect toward reducing body weight. But could these weight reductions lead to meaningful health outcomes?
A study published in Cardiovascular Drugs and Therapy suggests that over 90 million overweight or obese US adults could benefit from semaglutide helping to improve their blood pressure, blood glucose levels and lipid levels. Furthermore, patients with cardiovascular disease could have a 20% reduction in their risk of “major adverse cardiovascular events”. The researchers behind the study postulated that 93 million US adults may be suitable for semaglutide treatment, with the potential effect of reducing the number of people classed as obese by 43 million.
Continued dosing for long-term effects?
Given that obesity is a complex and chronic condition, it is important to question whether these drugs have a sustained effect on weight loss. Research suggests, possibly not, as one such study published in JAMA found that stopping the drugs can lead to weight regain.
In the SURMOUNT-4 study – also sponsored by drugmaker Eli Lilly – participants who stopped taking tirzepatide regained much of their lost weight within a year, suggesting that long-term use may be required to keep weight off. The study participants received 36 weeks of tirzepatide treatment, before they were randomly assigned into two groups: one group which continued with their treatment for another year, while the other switched to a placebo. Those who continued tirzepatide treatment reduced their body weight by a further 5.5%, while those who switched to a placebo regained 14% of their body weight.
Genetics may also play a role in the efficacy of these drugs, studies suggest, as well as the duration of treatment. A genome-wide association study (GWAS) published in Nature Genetics found that variations in the GLP-1R gene led to differences in study participants’ randomly tested blood glucose levels, and that, when lab-cultured cells were accordingly genetically modified, cells with these variants had different responses to GLP-1RAs. This suggests that patients with variations in the GLP-1R gene could also have differing responses to the drugs depending on their genetic makeup, possibly requiring more tailored treatments to be most effective.
Potential side effects
Though these drugs may be considered “blockbusters” due to their commercial success, their beneficial effects can, of course, come at the cost of negative side effects.
Gastrointestinal (GI) issues are some of the most reported side effects in clinical trials, including nausea, diarrhea and constipation. However, some evidence suggests that GLP-1RAs can result in more severe effects on the GI system, such as the potential for stomach paralysis, or gastroparesis. One study compared GLP-1RAs against another weight loss drug, bupropion-naltrexone, revealing GLP-1RAs led to a 3.67-fold higher risk of gastroparesis. There was also a 9.09-fold higher risk of pancreatitis and a 4.22-fold higher risk of bowel obstruction. Though these were still relatively rare, the number of people taking these drugs around the world today means that many more could experience these conditions.
Data on adverse events from earlier studies suggested that GLP-1RAs may be associated with an increased risk of developing thyroid tumors. However, a recent study by Karolinska Institute researchers found there was no increased risk of thyroid cancer associated with treatment with GLP1-RAs, such as liraglutide or semaglutide, over an average follow-up period of nearly four years.
Additionally, in 2023, a review by the European Medicines Agency (EMA) was also triggered in response to reports from the Icelandic Medicines Agency of thoughts of suicide and self-injury among people treated with GLP-1RAs. The regulator received and analyzed information on approximately 150 reported cases. However, a subsequent Nature Medicine study analyzed data from over 1.5 million US adults with type 2 diabetes and found no link between semaglutide and suicidal ideation compared to other non-GLP-1RA anti-obesity or anti-diabetes medications. Another concluded that there was no clear link between the use of GLP1-RAs and increased risk of suicide, self-harm, depression and anxiety-related disorders. In-depth investigations eventually led both the FDA and EMA to conclude that the available evidence does not support a link between the drugs and suicidal or self-injurious thoughts and actions.
The appearance of counterfeit drugs available online is another hurdle for these drugs to overcome. Unfortunately, shortages and supply chain issues have caused the demand for these drugs to outstrip supply. This has potentially fueled an increase in reports of fake medicines reported by the World Health Organization (WHO) Global Surveillance and Monitoring System. Confirmation of the reports led to an official warning – a medical product alert – from the WHO regarding increasing reports of falsified semaglutide since 2022.
Falsified GLP1-RA drug products have the potential to harm health, either from lacking the necessary ingredients to manage glucose levels or by containing other undeclared ingredients. This is important to consider in the wake of huge increases in the number of adolescents and young people aged 12–25 taking GLP1-RAs; one study found a striking 594% increase in the monthly number of people in this age group using GLP1-RAs such as Wegovy and Ozempic, making the need to tackle the uptick in falsified medicines even more pressing.
Potential for other conditions
The immense popularity of these drugs combined with the sheer number of people taking them has also highlighted several cases in which they appear to have beneficial effects against other, seemingly unrelated conditions.
For example, many patients undergoing GLP1-RA treatment for diabetes and weight loss report less of a desire to drink alcohol; something also supported by animal studies, which see decreases in drug and alcohol consumption. One study examining these anecdotal reports by patients on social media recruited 153 participants from various social media platforms who self-reported having obesity; one-third were taking semaglutide, one-third were taking tirzepatide and the remaining third were a control group. Those taking semaglutide and tirzepatide reported having significantly fewer drinks on average as well as significantly lower odds of binge drinking in comparison to the control group. Treatment of addiction disorders could therefore be another avenue for these drugs, with particular promise for alcohol use disorder, as the only three FDA-approved treatments for the condition have seen limited success.
They may also impact the risk of developing neurodegenerative disorders like dementia and Parkinson’s. A study that used target trial emulation – designed to imitate a randomized clinical trial – found that older people with type 2 diabetes who are treated with GLP1-RAs may have a lower risk of developing dementia. The study suggested that GLP1-RA-treated patients had a 30% lower risk of dementia compared to those taking other anti-diabetes drugs called sulfonylureas, and a 23% lower risk compared to those taking dipeptidyl peptidase-4 (DPP-4) inhibitors. Another similarly designed study found that semaglutide, in particular, may also lower the risk of Alzheimer’s disease among those with type 2 diabetes compared to seven other anti-diabetic drugs – including other GLP1-RAs.
Parkinson’s disease is another potentially promising treatment area, according to results from early trials. In a Phase 2 trial, the GLP1-RA drug lixisenatide led to slower progression of motor symptoms over a 12-month period among patients with Parkinson’s compared to those who took a placebo. However, additional and larger studies are still required to unravel the potential effects of these drugs for neurological conditions, as not all GLP1-RAs have a strong ability to enter the brain via the blood–brain barrier.
There is also evidence for a reduction in the risk of colorectal cancer, a disease that is on the rise, particularly among younger people under the age of 50. One study found that GLP1-RAs were associated with lower colorectal cancer risk in patients with type 2 diabetes regardless of whether they were obese/overweight – though the effect was stronger in overweight/obese patients.
More research still to be done
As these drugs continue to gain popularity and achieve commercial success, their list of indications may also proceed to expand in kind. The potential benefits of GLP1-RAs for other conditions, from reducing colorectal cancer risk and alcohol cravings to influencing the progression of some neurodegenerative diseases, could be more than we bargained for; but much more research remains to be carried out to confirm.