A first randomized clinical trial shows that semaglutide use in type 1 diabetes is associated with improved glucose management, weight loss and lower insulin requirements.
Semaglutide (known by its brandname Ozempic) has gained widespread attention for its weight loss benefits, but is officially approved for managing type 2 diabetes. While there is currently limited data on its risks and benefits for those with type 1 diabetes, new research offers promising insights.
A new study shows that semaglutide can improve glucose levels for people with type 1 diabetes who use automated pumps, without increasing hypoglycemia. In this double-blinded randomized trial conducted at the Centre for Innovative Medicine of the Research Institute of the McGill University Health Centre (The Institute), participants using semaglutide alongside automated insulin therapy were able to maintain safe glucose levels for longer periods. The results of the study were recently published in the journal Nature Medicine.
"The typical goal for patients with type 1 diabetes is to maintain a glycated hemoglobin (HbA1c) level of less than seven per cent, and to remain within the target glycemic range for 70 per cent or more of the time, in order to reduce the risk of microvascular and macrovascular complications. However, studies suggest that almost half of all people using automatic insulin pumps fail to achieve this," explains Dr. Michael Tsoukas, principal investigator of the study, Investigator in the Metabolic Disorders and Complications Program at The Institute and Associate Professor in the Division of Endocrinology, McGill University Health Centre (MUHC). "Our study shows that the addition of semaglutide can help them better manage the disease."
In type 1 diabetes, the pancreas is unable to produce insulin, a hormone that regulates glucose levels. As a result, people with diabetes must continuously monitor their blood glucose levels and provide their bodies with the amount of insulin they need to avoid complications. Achieving this goal can be facilitated by the use of an automated insulin delivery (AID) system, commonly known as an insulin pump, which allows for the automated administration of insulin doses that are adjusted in real time thanks to a glucose sensor and an algorithm that performs the necessary calculations.
"Multiple innovations have improved automated insulin delivery systems, which constitute the most advanced therapy for type 1 diabetes. For that reason, the placebo intervention, which consisted of using the AID with a weekly injection of a placebo, represented the best commercially available treatment and therefore the ideal point of comparison," says Ahmad Haidar, PhD, lead scientist of the study, Scientist in the Metabolic Disorders and Complications Program at The Institute and Associate Professor in the Department of Biomedical Engineering at McGill University.
The trial lasted a total of 32 weeks and included 28 adult participants. During the first 15 weeks, half of the participants injected themselves with a weekly dose of semaglutide, and the other half with a placebo, while continuing their own insulin therapy (22 of the 28 were using an insulin pump at the start of the trial). The dose of semaglutide was gradually increased up to 1 mg or the maximum tolerated dose. During the last 4 weeks of the 15, participants used a research-created automated insulin pump. After this intervention, participants took a two-week break and switched groups, so that those who had started on semaglutide took a placebo, and vice versa, for another 15 weeks.
Benefits associated with weight loss and lower insulin requirements
In the clinical trial, semaglutide use led to lower insulin requirements and increased weight loss. It showed greater benefits in participants with a higher body mass index, as they lost more weight and achieved greater glycemic benefits. This has important implications, since the prevalence of obesity in people with type 1 diabetes is increasing and is associated with the risk of cardiovascular disease and complications.
While no diabetic ketoacidosis-a life-threatening complication of diabetes-or severe hypoglycemia occurred during the trial, there were two episodes of recurrent high ketone levels without high blood sugars or acidosis that occurred while participants were using semaglutide. High ketone levels can occur in people with type 1 diabetes when there is not enough insulin for the body to absorb sugar, so the body breaks down fat instead; at very high levels, this can make blood acidic and cause severe illness. Gastro-intestinal side effects were also associated with semaglutide.
"We know that off-label use of semaglutide is rising in people with type 1 diabetes, despite a lack of information to guide patients and healthcare providers on the benefits and risks associated with it," says Dr. Melissa-Rosina Pasqua, the study's first author, endocrinologist at the MUHC and doctoral student at The Institute, who coordinated the study. "This study addresses a current treatment gap and is an important stepping stone in demonstrating the benefits of this drug, as well as the ongoing need to educate patients about the risks of high ketone levels."
About the study
The study Subcutaneous weekly semaglutide with automated insulin delivery in type 1 diabetes: a double-blind, randomized, crossover trial was conducted by Melissa-Rosina Pasqua, Michael A. Tsoukas, Alessandra Kobayati, Wedyan Aboznadah, Adnan Jafar and Ahmad Haidar.
DOI: https://doi.org/10.1038/s41591-024-03463-z
This work was funded by Professor Ahmad Haidar's Canada Research Chair in Artificial Pancreas systems.
