Simple meal announcements and pramlintide delivery versus carbohydrate counting in type 1 diabetes with automated fast-acting insulin aspart delivery: a randomised crossover trial in Montreal, Canada.

BACKGROUND

In type 1 diabetes, carbohydrate counting is the standard of care to determine prandial insulin needs, but it can negatively affect quality of life. We developed a novel insulin-and-pramlintide closed-loop system that replaces carbohydrate counting with simple meal announcements.

METHODS

We performed a randomised crossover trial assessing 14 days of (1) insulin-and-pramlintide closed-loop system with simple meal announcements, (2) insulin-and-placebo closed-loop system with carbohydrate counting, and (3) insulin-and-placebo closed-loop system with simple meal announcements. Participants were recruited at McGill University Health Centre (Montreal, QC, Canada). Eligible participants were adults (aged ≥18 years) and adolescents (aged 12-17 years) with type 1 diabetes for at least 1 year. Participants were randomly assigned in a 1:1:1:1:1:1 ratio to a sequence of the three interventions, with faster insulin aspart used in all interventions. Each intervention was separated by a 14-45-day wash-out period, during which participants reverted to their usual insulin. During simple meal announcement interventions, participants triggered a prandial bolus at mealtimes based on a programmed fixed meal size, whereas during carbohydrate counting interventions, participants manually entered the carbohydrate content of the meal and an algorithm calculated the prandial bolus based on insulin-to-carbohydrate ratio. Two primary comparisons were predefined: the percentage of time in range (glucose 3·9-10·0 mmol/L) with a non-inferiority margin of 6·25% (non-inferiority comparison); and the mean Emotional Burden subscale score of the Diabetes Distress Scale (superiority comparison), comparing the insulin-and-placebo system with carbohydrate counting minus the insulin-and-pramlintide system with simple meal announcements. Analyses were performed on a modified intention-to-treat basis, excluding participants who did not complete all interventions. Serious adverse events were assessed in all participants. This trial is registered on ClinicalTrials.gov, NCT04163874.

FINDINGS

32 participants were enrolled between Feb 14, 2020, and Oct 5, 2021; two participants withdrew before study completion. 30 participants were analysed, including 15 adults (nine female, mean age 39·4 years [SD 13·8]) and 15 adolescents (eight female, mean age 15·7 years [1·3]). Non-inferiority of the insulin-and-pramlintide system with simple meal announcements relative to the insulin-and-placebo system with carbohydrate counting was reached (difference -5% [95% CI -9·0 to -0·7], non-inferiority p<0·0001). No statistically significant difference was found in the mean Emotional Burden score between the insulin-and-pramlintide system with simple meal announcements and the insulin-and-placebo system with carbohydrate counting (difference 0·01 [SD 0·82], p=0·93). With the insulin-and-pramlintide system with simple meal announcements, 14 (47%) participants reported mild gastrointestinal symptoms and two (7%) reported moderate symptoms, compared with two (7%) participants reporting mild gastrointestinal symptoms on the insulin-and-placebo system with carbohydrate counting. No serious adverse events occurred.

INTERPRETATION

The insulin-and-pramlintide system with simple meal announcements alleviated carbohydrate counting without degrading glucose control, although quality of life as measured by the Emotional Burden score was not improved. Longer and larger studies with this novel approach are warranted.

FUNDING

Juvenile Diabetes Research Foundation.

Informations de copyright

Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC 4.0 license. Published by Elsevier Ltd.. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests MAT received speaker honoraria from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Janssen, Novo Nordisk, and Sanofi. LL received research support from AstraZeneca and Merck; consultant fees from Abbott, Dexcom, Insulet, and Novo Nordisk; payment or honoraria and support for attending meetings or travel from Novo Nordisk; and participated on a data safety monitoring board and advisory board for the National Institutes of Health artificial pancreas programme. MV received research support from Abbott, Bausch Health, and Novo Nordisk; consultant fees from AbbVie, Abbott, Bausch Health, Boehringer Ingelheim, Lifescan, Lyceum, Novo Nordisk, Roche, and Sanofi; and speaker honoraria from Abbott, AbbVie, Bausch Health, Lifescan, Lilly, Merck, Novo Nordisk, Pfizer, Roche, and Sanofi. J-FY received research support from Bayer, Novo Nordisk, Novartis, and Sanofi; consultant fees from Abbott, Bayer, Boehringer Ingelheim, Dexcom, Eli Lilly, Janssen, Merck, Mylan, Novo Nordisk, and Sanofi; and speaker honoraria from Novo Nordisk and Eli Lilly. NG-P is employed by Tandem Diabetes Care. AH received research support from Adocia, Dexcom, Eli Lilly, and Tandem Diabetes Care; equipment, materials, drugs, medical writing, gifts, or other services from Dexcom, Ypsomed, and Tandem Diabetes Care; consulting fees from Eli Lilly; and intellectual property acquisition fees from Eli Lilly and Bigfoot. All other authors declare no competing interests.