Project summary/Abstract
One of the main challenges in maintaining tight glucose control in individuals with type 1 diabetes
(T1D) occurs at mealtimes. Current intensive insulin therapy in T1D involves prandial insulin
boluses dependent on the carbohydrate content of the ingested meal. However, accurate
carbohydrate counting is a challenging and burdensome task for many individuals with T1D. In
this proposal, we aim to simplify mealtime diabetes management with a combination of glucose-
lowering drugs and our automated insulin delivery (AID) system using Lyumjev.
Glucagon-Like-Peptide-1 is a hormone released by gut endocrine cells in response to glucose
consumption. Exogenous GLP-1 receptor agonists (GLP-1 RAs) have been developed to
decrease fasting and postprandial blood glucose by (i) increasing insulin secretion, (ii) decreasing
glucagon secretion, (iii) slowing gastric emptying, and (iv) reducing appetite by stimulating satiety
brain centers. Randomized controlled trials in type 2 diabetes have shown that GLP-1 RAs
improve glucose control without increasing hypoglycemia, and recent data in type 1 diabetes have
also shown promising results. Lyumjev is a novel ultra-rapid insulin lispro formulation with a faster
onset of insulin action compared to the conventional insulin lispro – Humalog. Delivering Lyumjev
at mealtimes significantly lowers postprandial glucose levels and reduces post-meal incremental
area under the curve compared to Humalog.
We aim to conduct a 2 × 2 factorial, randomized, placebo-controlled, double-blind, crossover trial
to assess if the addition of Semaglutide to an AID system with Lyumjev can alleviate the burden
of carbohydrate counting, without degrading daytime glucose control in 26 adults with T1D. The
study will consist of 4 interventions, each 4-weeks in length, testing Semaglutide-plus-lyumjev
with (i) a system that requires carb counting (AID-count) and (ii) a system that requires meal
announcement only (AID-announce), as well as placebo-plus-lyumjev with (iii) AID-count and (iv)
AID-announce. The order of the of the drug sequence (Semaglutide vs placebo) will be
randomized 1:1. Within each drug sequence, the order of the AID configuration will also be
randomized 1:1. At the start of each drug sequence, 12-week dose titration period will be initiated.
A 2-week washout period will be applied between the drug sequences. The primary outcome is
the daytime (6:00-24:00) percentage of time spent in the target glucose range (TIR), defined as
70-180mg/dL, over 4 weeks between sema-plus-lyumjev-AID-announce and placebo-plus-
lyumjev-AID-count (control arm). We hypothesize that sema-plus-lyumjev-AID-announce will
achieve non-inferior daytime TIR compared to the control arm.
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