Semaglutide improves glycemic control with automated insulin delivery

GLP-1 and insulin combo shows promise for type 1 diabetes with lower insulin needs, improved glucose control, and weight loss

Therapies for type 1 diabetes

At present, the AID is the most advanced form of insulin therapy for T1D. AID involves continuous glucose monitoring (CGM), and an algorithm is adjusted to insulin dosage based on blood glucose levels.

Previous studies have indicated that the use of AID effectively reduces glycated hemoglobin (HbA1c) in diabetic patients. In comparison to other conventional diabetes treatments, this treatment strategy enables a quicker resolution to the normal target glucose range of 3.9–10.0 mmol/l.

As per diabetes guidelines, it is essential to maintain an HbA1c of less than 7% to reduce the risk of microvascular and macrovascular diabetes complications. Large randomized trials that were previously conducted indicated that 34–53% of participants were not able to achieve an HbA1c of less than 7% through AID treatment, primarily due to suboptimal postprandial glucose control.

Multiple studies have highlighted the glycemic, weight, and cardiac benefits of semaglutide, a glucagon-like peptide-1 receptor agonist (GLP1-RA), treatment in patients with or without type 2 diabetes (T2D). Typically, semaglutide is subcutaneously administered once weekly. To date, no clinical trials have been conducted to investigate the effect of semaglutide against T1D.

About the study

The current study performed a randomized, double-blind, crossover trial at the Research Institute of the McGill University Health Centre in Montreal, Quebec, Canada, to investigate whether semaglutide improved glycemic control and other nonglycemic outcomes in patients with T1D and using AID.

It was a 32-week trial, with each treatment lasting 15 weeks and a two-week washout period. The current study recruited individuals 18 years of age and older with a T1D diagnosis for at least one year or longer. Each participant used an insulin pump for three months or longer, and their estimated HbA1c was 11% or less.

The selected participants were asked to use birth control or actively avoid pregnancy during the trial. Individuals with a BMI of 21 kg/m² or less or had a history of acute or chronic pancreatitis, gallbladder disease, medullary thyroid cancer, or type 2 multiple endocrine neoplasia were excluded from the study.

Participants’ demographic data, including their age, medical history, medications, and duration of diabetes, were obtained. At baseline, a physical examination and laboratory tests were conducted.

An eleven-week semaglutide drug dose titration period was started, and during this period, all participants continued using their usual pump therapy. The side effects and CGM reports were assessed on days 7, 21, 32, 56, 63, and 77 of the dose titration periods. As per requirement, insulin dosage was adjusted to prevent hypoglycemia and overt hyperglycemia.

After the dose titration period, participants were subjected to the research-based AID system for 28 days. This study used a Ypsomed insulin pump (Ypsomed), Dexcom G6 CGM (Dexcom), and a Pixel 2 smartphone with an application running the McGill insulin dosing algorithm. Remote follow-ups were carried out. After the end of AID use, participants received their usual insulin for a washout period of 2 weeks, following which the second study drug was initiated.

Study findings

A total of 113 adults with T1D were screened, among which 28 candidates (61% female and HbA1c of 7.4%) were recruited. Of these, 24 participants completed the trial. Approximately 8.3% of participants exhibited maximum semaglutide dose tolerance (0.25 mg), followed by 0.5 mg and 1 mg by 25.0% and 66.7% of participants, respectively.

The study findings indicated that semaglutide improved glycemic control with lower insulin requirements in adults with T1D when used with AID. In comparison to placebo treatment, a reduced carbohydrate intake and decreased body weight, BMI, waist, and hip circumferences were associated with semaglutide treatment. Participants with higher weight reduction exhibited greater glycemic benefits.

HbA1c reductions were found to be higher in those with detectable C-peptide levels compared to those without undetectable levels. Prominent glycemic and anthropometric benefits were linked to the use of semaglutide as an adjunct to AID therapy.

However, no significant benefits were observed in nonglycemic laboratory outcomes and blood pressure, which could be attributed to the lack of abnormalities in participants at baseline. Although changes in bilirubin, HDL-c, and alkaline phosphatase were noted, they were not statistically significant.

The most common adverse events (AEs) were gastrointestinal. Although diabetic ketoacidosis did not occur, two participants developed euglycemic ketosis during semaglutide use. One participant with a placebo developed severe hypoglycemia due to CGM malfunction.

Conclusions

The current study revealed that semaglutide, as an adjunct to AID in T1D patients, particularly in those with higher BMI, caused greater weight loss and higher glycemic benefits. Despite the benefits, one must be cautious to prevent ketoacidosis. In the future, the long-term efficacy and safety of semaglutide along with AID need to be assessed using a larger cohort.

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