Diabetes and obesity: new evidence on semaglutide in relation to the heart, kidneys and safety

New data on the molecule and the ESC guidelines have been released, whilst a Northern European observational study has found no increase in pancreatic cancer

by Francesca Cerati

29 September 2026

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Semaglutide pill, conceptual image. WLADIMIR BULGAR/SCIENCE PHOTO LIBRARY / AGF

3' min read

Translated by AI

Versione italiana

3' min read

Translated by AI

Versione italiana

Semaglutide is broadening the scope of evidence, from diabetes and weight management to cardio-renal protection, whilst new data are also helping to define the molecule’s safety profile. At the heart of the latest developments presented at the EASD Congress in Milan are the new European guidelines on cardiovascular disease and chronic kidney disease, the results of the most recent trials on oral formulations, and an observational study on the potential risk of pancreatic cancer.

What do the guidelines

set out?

The first step concerns the ESC 2026 Guidelines, developed in collaboration with the European Renal Association and, for the first time, specifically dedicated to the intersection between cardiovascular disease and chronic kidney disease. For people with type 2 diabetes and chronic kidney disease, the document recommends semaglutide – provided the criteria set out in the guidelines are met – to reduce the progression of kidney disease and the risk of cardiovascular events.

The recommendation is supported in particular by the results of the Flow study, which involved 3,533 people with type 2 diabetes and chronic kidney disease. Weekly treatment with semaglutide reduced the risk of the composite renal endpoint by 24 per cent; this endpoint included kidney failure, a sustained reduction of at least 50 per cent in eGFR (estimated glomerular filtration rate) or death from renal or cardiovascular causes. The trial also showed a reduction of around one-third in the rate of eGFR decline and, on the cardiovascular front, an 18 per cent reduction in the composite endpoint comprising non-fatal myocardial infarction, non-fatal stroke or cardiovascular death.

This also applies to people who are overweight or obese. In the Select study, conducted in people with pre-existing cardiovascular disease but without diabetes, semaglutide 2.4 mg reduced the risk of the primary cardiovascular endpoint by 20% and a pre-specified composite renal endpoint by 22%. The new European guidelines also highlight the role of obesity as a risk factor for heart and kidney disease and consider GLP-1 receptor agonists in patients with heart failure with preserved ejection fraction, chronic kidney disease and obesity, with the aim of promoting weight loss and improving quality of life.

Simpler, more customisable treatments

At the same time, research is moving towards simpler and more personalised treatment options. In type 2 diabetes, one of the most eagerly awaited developments is the combination of basal insulin and semaglutide in a single weekly dose. According to data presented at the conference, this strategy can reduce the burden of injections, maintain glycaemic control and offer benefits in terms of weight management, with lower rates of hypoglycaemia. This is a particularly relevant issue because, according to data presented by the experts, around 30 per cent of people with type 2 diabetes who require insulin in Italia delay starting treatment by more than two years.

On the obesity front, the other development concerns the oral formulation. In the Oasis 4 study, semaglutide in tablet form resulted in an average weight loss of 17 per cent, reaching around 22 per cent in a third of participants. The results, as reported, are accompanied by a safety profile consistent with that previously observed for the injectable formulation. The option of taking the treatment orally thus offers an alternative for eligible individuals who prefer to avoid, at least initially, an injectable therapy.

Data on pancreatic safety

Completing the picture are the pancreatic safety data presented at the EASD in Milan. A post-authorisation study conducted using national health registries from Denmark, Sweden and Norway compared 97,464 users of semaglutide with a cohort of people treated with other non-incretin antidiabetic drugs. The study, commissioned by the regulatory authorities specifically to assess the potential risk of pancreatic cancer and funded by Novo, found no increased risk.

During the observation period, 131 cases of pancreatic cancer were recorded amongst semaglutide users and 123 in the comparison group. The pooled analysis of the three countries yielded a hazard ratio of 0.91, with a 95 per cent confidence interval of 0.71 to 1.16. Furthermore, no evidence of a dose-related or duration-related effect was observed.

The findings therefore help to add to the safety profile of semaglutide, but should be interpreted with caution. This is, in fact, an observational study funded by the manufacturer, which was presented at a conference but has not yet been published in a scientific journal and has therefore not undergone peer review. The data do not indicate an increased risk in the comparison under consideration, but do not in themselves constitute absolute proof of the absence of risk.

The common thread running through the various pieces of evidence is therefore the gradual shift in the therapeutic focus: from simply controlling blood glucose levels or reducing weight to a broader management of metabolic, cardiovascular and renal risk, alongside the search for treatment options that are compatible with everyday life and an increasingly comprehensive assessment of safety.