We have really good evidence that there are cardiovascular and renal benefits of GLP-1s, particularly the newer agents, in other populations, in type 2 diabetes, and in people with obesity. And cardiovascular disease remains a major complication of type 1 diabetes. What we found in our study was that adults with obesity who are already using the standard of care and automated insulin delivery systems can benefit from the use of adjunctive therapy with GLP-1s. Hello, I’m Dr Janet Snell-Bergeon, and I’m a professor of paediatrics and epidemiology at the University of Colorado at the Barbara Davis Center for Diabetes. People with type 1 diabetes have limited treatment options currently, really with just insulin available to them. And with advances in insulin treatment, people have been able to go on automated insulin delivery devices, but many people still remain above goal for haemoglobin A1c, even on these advanced technologies. So, there’s really a need for adjunctive therapies to help people achieve those targets, despite their reliance on insulin. Earlier results from clinical trials didn’t demonstrate benefit for people with type 1 diabetes with GLP-1s, but those earlier agents were less potent in terms of the effect on glycaemic control and on weight loss. And, for example, some of them were daily injections. And now we have weekly injections that are a little bit stronger in terms of their effect on glycaemic control and weight loss. And we have really moved towards putting more people on diabetes technology that helps prevent some of the hypoglycaemia and hyperglycaemia that was observed in some of the earlier trials. In addition, we have really good evidence that there are cardiovascular and renal benefits of GLP-1s, particularly the newer agents, in other populations, in type 2 diabetes and in people with obesity. And cardiovascular disease remains a major complication of type 1 diabetes. The rationale for the study was that GLP-1s seemed to be improving glycaemic control as well as reducing the need for insulin in people with type 2 diabetes. So, we designed a randomised clinical trial. We conducted it at four sites in the United States over 26 weeks, and people were randomised to either a dose of semaglutide, up to 1 mg per week, or placebo. Participants were followed periodically for examination of their weight and their HbA1c. And they also wore a continuous glucose monitor. All of the participants in the study had to be obese and they had to have an A1c above goal, so above 7 %. And they also had to be wearing an automated insulin delivery system, and so everyone was wearing a CGM. So, we looked at time in range, time below range and other CGM metrics as part of our key outcomes. The primary outcome of the study was achieving a composite endpoint, which included achieving weight loss of at least 5 %, achieving a time in range of greater than 70 %, and achieving time below range of less than 4 %. We examined as our primary outcome the percentage of people in the semaglutide-treated group versus the placebo group that were able to achieve this composite outcome. And what we observed was that 36 % of treated patients in the semaglutide group were able to achieve this outcome versus none of the participants in the placebo group. So this difference was significant with an odds ratio of over 7 %. There was substantial weight loss. So, 75 % of the participants in the semaglutide-treated group were able to achieve at least 5 % weight loss. Also, more of them were able to achieve better glycaemic control with an improvement in A1c. So, the difference between the placebo and the treated group was -0.3 % for HbA1c. So, we saw a modest effect on improvement in glycaemic control. We also did see a difference in the insulin dose required. So, participants who were randomised to semaglutide required less insulin per day, more than 22 units decrease in their daily dose, and that translated also to a 0.17 units per kilogram reduced dose of insulin per day. So, we think it’s a combination of weight loss as well as reduced insulin requirements that could have contributed to our findings. What we did see was that people had an immediate improvement in their glycaemic control and reduction in their insulin dose at even as early as four weeks in the study. And meanwhile, their weight loss continued to accrue over the 26 weeks, and so they didn’t achieve the weight loss at the same time as the improvements in metabolic health. And so, we think that there may be different mechanisms at work. Certainly, AIDs make a big difference in terms of improving people’s glycaemic control, but there still remain more than half of adults with type 1 diabetes that aren’t able to achieve glycaemic targets, even using these advanced systems. I think that in the study it was important for us to use the AID, because it is the standard of care now for people with type 1 diabetes. So, we feel like adjunctive therapy should be added onto the best already available care. But certainly, AID systems and insulin are not enough. So, we see that there’s great potential for improving people’s other cardiovascular and renal health as well as allowing them to achieve targets using these newer GLP-1 agents. What we found in our study was that adults with obesity who are already using the standard of care and automated insulin delivery systems can benefit from the use of adjunctive therapy with GLP-1s. We don’t know yet if this kind of benefit could be available to people with a lower body mass index because there could be more severe side effects. So, that remains to be determined. We also had a very promising safety profile in our study. We had no events of diabetic ketoacidosis, and we had two severe hypoglycaemic events in each group. So, there was no difference by treatment group in terms of safety outcomes. So, the study really shows that these agents can be used safely and effectively, at least in obese adults with type 1 diabetes.