Editorial: Advances in insulin and GLP-1 RAs continue at pace

In many of my recent editorials, I have alluded to the next generation of advancements in both insulin and incretin therapies. So, I thought I would take this opportunity to concentrate the bulk of this editorial on breaking news in these classes. 

We had been waiting with bated breath for the anticipated launch of icodec, a once-weekly basal insulin, only to receive the unbelievably disappointing news that Novo Nordisk is not planning to launch it in the UK. However, we now have encouraging news regarding the development of Eli Lilly’s once-weekly insulin efsitora. 

Among the findings from the QWINT-1 study (part of the wider QWINT programme), which were reported at the recent American Diabetes Association’s Scientific Sessions in Chicago, was a reduction in hypoglycaemia rates in insulin-naïve adults with efsitora compared with insulin glargine. My hope is that this will be launched in the UK to provide hope to the many cohorts of insulin-requiring patients, particularly the elderly, who find traditional dosing algorithms a burden. If all goes well, Lilly will be looking to submit marketing-authorisation applications to the global regulatory authorities later this year. The wait continues…

Levemir (insulin detemir) is to be discontinued, with supply anticipated to end in December 2026. We have been awaiting national guidance to prepare for this discontinuation, so it is good news that I can point you to new guidance from the Association of British Clinical Diabetologists and the Primary Care Diabetes & Obesity Society. It provides invaluable support to clinicians in appropriately selecting and safely prescribing alternative insulin therapies. It will, I am sure, be of immense use as we manage this transition for the thousands of people on this preparation nationally. 

Weight-management developments reach break-neck speed

The news regarding the pricing of the dual incretin mimetic tirzepatide (marketed by Eli Lilly as Mounjaro) is that we have been assured that the prescription price is secure, but the cost for private purchase of the highest dose of the drug looks set to increase by an astonishing 170%. The reasons are multifactorial but will, hopefully, secure demand for those who meet NHS criteria. However, given the number of people accessing this medication privately, we can only imagine the increase in demand for Mounjaro from primary care. Our colleagues are already facing a monumental number of requests from people who, as yet, do not meet the strict phased roll-out criteria discussed in my April editorial.

Lilly also has in development an oral GLP-1 receptor agonist, orforglipron. Unlike Rybelsus (oral semaglutide), which requires specific administration in the morning on an empty stomach with minimal water to maximise bioavailability, orforglipron is a non-peptide and can be taken at any time of day with no food or water restrictions. This would certainly be advantageous for a wide cohort of people. If licensing goes to plan, this could be available in late 2026.

Novo Nordisk has in development its next generation of weight-loss medication. CagriSema is a combination of cagrilintide and semaglutide. While semaglutide activates GLP-1 receptors to reduce appetite, cagrilintide increases satiety by binding to the amylin receptors in the brain. Amylin is a glucoregulatory peptide hormone that slows gastric emptying, thereby increasing a feeling of fullness and reducing calorific intake. Additionally, it suppresses glucagon to help manage blood glucose levels. The anticipated launch, if regulatory approval is achieved, would be late 2026.

Maridebart cafraglutide (also known as MariTide), for administration at monthly intervals or less frequently, is a first-in-class therapy being developed for the treatment of obesity in those with or without diabetes. You will all be familiar with tirzepatide, a single synthetic peptide molecule modified to bind to both GIP and GLP-1 receptors, which is currently the only dual agonist available. MariTide, by contrast, is a large molecule comprising a monoclonal antibody antagonist to the GIP receptor conjugated to two identical GLP-1 peptide analogues. It is now entering phase 3 trials.

Good news arrived with the results from ADJUST-T1D. This study looked at the safety and efficacy of once-weekly semaglutide use in adults with poorly controlled type 1 diabetes, a BMI >30 kg/m² and who were using a hybrid closed-loop system. It found that semaglutide significantly increased time in range and reduced HbA_1c, while no episodes of DKA were reported. Positive news, indeed!

I often hear concerns raised about the huge weight loss experienced by some on incretin therapies. Most commonly, they relate to whether there is a need to take nutritional supplements in the long term and to the amount of lean mass loss that contributes to the total weight loss experienced. It was with interest, therefore, that I read that the findings from the BELIEVE study. In this study, a group of obese adults received intravenous bimagrumab (a monoclonal antibody that targets activin type II receptors, which play a role in muscle growth and fat metabolism) as well as semaglutide treatment. At the highest doses, the weight loss attributable to lean mass was significantly lower than with semaglutide alone. With a phase 2 study underway, it is hoped that by combining GLP-1 RA therapy with bimagrumab, the benefits of significant weight loss will be reaped while muscle mass is protected. Watch this space for updates.

Many of these developments were announced at the ADA conference, which remains a very busy and exciting annual event. You can read further summaries and access links to the trials mentioned in our conference news article.