Adjunctive Therapies to Optimize Closed-loop Glucose Control

Abstract

Closed-loop insulin delivery systems are fast becoming the standard of care in the management of type 1 diabetes and have led to significant improvements in diabetes management. Nevertheless, there is still room for improvement for the closed-loop systems to optimize treatment and meet target glycemic control. Adjunct treatments have been introduced as an alternative method to insulin-only treatment methods to overcome diabetes treatment challenges and improve clinical and patient reported outcomes during closed-loop treatment. The adjunct treatment agents mostly consist of medications that are already approved for type 2 diabetes treatment and aim to complete the missing physiologic factors, such as the entero-endocrine system, that regulate glycemia in addition to insulin. This paper will review many of these adjunct therapies, including the basic mechanisms of action, potential benefits, side effects, and the evidence supporting their use during closed-loop treatment.

Safety and Efficacy of the Omnipod 5 Automated Insulin Delivery System in Adults With Type 2 Diabetes: From Injections to Hybrid Closed-Loop Therapy

“…Although those not using these medications also experienced substantial improvements, these results suggest that those using AID in conjunction with GLP-1 RAs and/or SGLT-2 inhibitors may experience greater benefit than those not using these medications; however, additional research is needed to confirm whether this trend is reproducible. These outcomes are not surprising; several studies have already investigated the use of GLP-1 RAs and SGLT-2 inhibitors alongside AID in people with type 1 diabetes, with promising results reported (27)(28)(29).…”

Contributions to glucagon and pramlintide pharmacokinetics and pharmacodynamics modeling for multi-hormone artificial pancreas systems

“…Its use is not as extended as those of insulin and glucagon, but it has proven useful in reducing postprandial hyperglycemia, and a 1-year long trial showed that pramlintide significantly helped to reduced HbA1c 4 values (Ratner et al, 2004). Pramlintide was approved for its use in T1D treatment by the FDA (U.S. Food and Drug Administration) in 2005 (Srinivasan et al, 2021). A posterior meta-analysis (Qiao et al, 2017) gathered ten clinical trials with pramlintide from 1997 to 2016, to analyze its efficacy and safety.…”

“…Cardiac risks (Blonde et al, 2022), but fewer side effects than GLP-1 (Ang and Sherr,2017). Used in T2D,but trials in T1D do not show many potential benefits (Drucker et al, 2010;Ang and Sherr, 2017;Srinivasan et al, 2021).…”

“…Used in T2D, but with significant adverse effects. (Srinivasan et al, 2021). Trials in T1D are showing positive outcomes (Ang and Sherr, 2017), but there is a risk of elevated ketones.…”

“…In the review by Srinivasan et al (2021), there is a reference to a 2019 conference abstract of a CL study with dapagliflozin. The proper results of the trial were later presented in the work by Biester et al (2021).…”