Once-weekly insulin efsitora alfa versus once-daily insulin degludec in adults with type 2 diabetes currently treated with basal insulin (QWINT-3): a phase 3, randomised, non-inferiority trial.

Background: Once-weekly insulin efsitora alfa (efsitora) is in development for the treatment of people with diabetes. The aim of the current study was to assess the efficacy and safety of once-weekly efsitora compared with daily insulin degludec (degludec) in adults with type 2 diabetes using basal insulin.

Methods: This randomised, 78-week, phase 3, parallel-design, open-label, treat-to-target, non-inferiority study (QWINT-3) was conducted at 127 sites across nine countries.

Weekly Fixed-Dose Insulin Efsitora in Type 2 Diabetes without Previous Insulin Therapy.

Background: In previous treat-to-target trials, adjustments to the dose of basal insulin have been made at least weekly, according to fasting blood glucose levels. A fixed-dose regimen of insulin efsitora alfa (efsitora), a once-weekly basal insulin, may provide a benefit in adults with type 2 diabetes who have not received previous insulin therapy.

Methods: We conducted a 52-week, phase 3, open-label, treat-to-target trial involving adults with type 2 diabetes who had not previously received insulin therapy.

Accuracy of the 15.5-Day G7 iCGM in Adults with Diabetes.

Continuous glucose monitors (CGM) are increasingly being used to manage diabetes. We evaluated the performance and safety of an investigational 15-day G7 integrated CGM (iCGM; Dexcom) in adults with diabetes. This prospective, multicenter study enrolled adults (age ≥18 years) with type 1 diabetes (T1D) or type 2 diabetes (T2D) at six clinical sites in the United States.

Evaluation of Accuracy and Safety of the 365-Day Implantable Eversense Continuous Glucose Monitoring System: The ENHANCE Study.

The implanted Eversense Continuous Glucose Monitoring (CGM) System transitioned from 90- to 180- to 365-day durations marketed today. This report summarizes the 365-day clinical study. ENHANCE was a prospective, multicenter study evaluating the accuracy and safety of the Eversense 365 CGM system through 1 year in adults with diabetes.

A post-hoc pooled analysis to evaluate efficacy and safety of insulin glargine 300 U/mL in insulin-naïve people with type 2 diabetes with/without prior use of glucagon-like peptide-1 receptor agonist therapy.

Aims: To evaluate treatment advancement with insulin glargine 300 U/mL (Gla-300), with or without prior glucagon-like peptide-1 receptor agonist (GLP-1 RA) therapy in type 2 diabetes (T2D).

Methods: Efficacy and safety outcomes of insulin-naïve patients intensifying with Gla-300, with/without prior GLP-1 RA therapy, were evaluated in three analyses (N = 3562): a pooled analysis of seven interventional studies, a subanalysis comparing participants who stopped GLP-1 RA therapy and initiated Gla-300 with those who received add-on Gla-300, and an expanded analysis including two observational studies.

Results: Glycaemic outcomes, including HbA1c improvement and fasting plasma glucose, were similar between groups with/without prior GLP-1 RA use.

Development of a Real-Time Dashboard for Overdose Touchpoints: User-Centered Design Approach.

Background: Overdose Fatality Review (OFR) is an important public health tool for shaping overdose prevention strategies in communities. However, OFR teams review only a few cases at a time, which typically represent a small fraction of the total fatalities in their jurisdiction. Such limited review could result in a partial understanding of local overdose patterns, leading to policy recommendations that do not fully address the broader community needs.

Frequency of hypoglycaemia with basal insulin treatments in adults with type 1 diabetes treated with basal-bolus insulin regimens in treat-to-target trials: A narrative review.

Aim: To summarise, in a narrative review, published data on hypoglycaemia occurrence with basal insulin therapy in adults with type 1 diabetes treated with basal-bolus insulin regimens in treat-to-target randomised controlled trials.

Methods: Data were included from 21 eligible trials, which mainly used self-measured blood glucose or plasma glucose to detect hypoglycaemia.

Results: All-day self-measured blood glucose or plasma glucose level 2 (glucose threshold of 3.

Opportunities to overcome underutilization of enhanced insulin delivery technologies in people with type 2 diabetes: a narrative review.

Use of innovative technologies such as continuous glucose monitoring (CGM) and insulin delivery systems have been shown to be safe and effective in helping patients with diabetes achieve significantly improved glycemic outcomes compared to their previous therapies. However, these technologies are underutilized in many primary care practices. This narrative review discusses some of the clinical and economic benefits of tubeless insulin delivery devices and discusses how this technology can overcome the main obstacles inherent to use of conventional insulin delivery devices.

Safety and Efficacy of Switching SAR341402 Insulin Aspart and Originator Insulin Aspart vs Continuous Use of Originator Insulin Aspart in Adults With Type 1 Diabetes: The GEMELLI X Trial.

Background: SAR341402 insulin aspart (SAR-Asp) is a rapid-acting insulin analog developed as an interchangeable biosimilar to the marketed insulin aspart reference product (NovoLog; NN-Asp). GEMELLI X was a randomized controlled trial to assess outcomes with a biosimilar in line with the US Food and Drug Administration requirements for designation as an interchangeable biosimilar. This report assessed whether multiple switches between SAR-Asp and NN-Asp lead to equivalent safety and efficacy compared with continuous use of NN-Asp in adults with type 1 diabetes (T1D) treated with multiple daily injections, using once-daily insulin glargine U100 (Lantus) as the basal insulin.

Comparator Data Characteristics and Testing Procedures for the Clinical Performance Evaluation of Continuous Glucose Monitoring Systems.

Comparing the performance of different continuous glucose monitoring (CGM) systems is challenging due to the lack of comprehensive guidelines for clinical study design. In particular, the absence of concise requirements for the distribution of comparator (reference) blood glucose (BG) concentrations and their rate of change (RoC) that are used to evaluate CGM performance, impairs comparability. For this article, several experts in the field of CGM performance testing have collaborated to propose characteristics of the distribution of comparator measurements that should be collected during CGM performance testing.

Modeling methyl-sensitive transcription factor motifs with an expanded epigenetic alphabet.

Background: Transcription factors bind DNA in specific sequence contexts. In addition to distinguishing one nucleobase from another, some transcription factors can distinguish between unmodified and modified bases. Current models of transcription factor binding tend not to take DNA modifications into account, while the recent few that do often have limitations.

Pharmacokinetic similarity of switching SAR341402 insulin aspart biosimilar and NovoLog insulin aspart versus continuous use of NovoLog in adults with type 1 diabetes: The GEMELLI X trial.

Aim: To assess whether multiple switches between SAR341402 biosimilar insulin aspart (SAR-Asp) and the insulin aspart reference product (NovoLog; NN-Asp) leads to equivalent pharmacokinetic (PK) exposure compared with continuous use of NN-Asp in adults with type 1 diabetes (T1D).

Materials And Methods: This multicentre, open-label, phase 3 study randomized (1:1) 210 subjects with T1D treated with once-daily insulin glargine U100 as basal insulin to four 4-week periods of alternating multiple daily injections of SAR-Asp and NN-Asp (NN-Asp for the first 4 weeks, SAR-Asp in the last 4 weeks; switching group) versus 16 weeks of continuous NN-Asp (non-switching group). At week 16, a single dose (0.

Antecedents of fatal overdose in an adult cohort identified through administrative record linkage in Indiana, 2015-2022.

Background: The United States continues to experience unprecedented rates of overdose mortality and need to identify effective policies or practices that can be implemented. This study aims to measure the prevalence, frequency, timing, and rate of touchpoints that occurred prior to a fatal overdose where communities might intervene.

Methods: In collaboration with Indiana state government, we conducted record-linkage of statewide administrative datasets to vital records (January 1, 2015, through August 26, 2022) to identify touchpoints (jail booking, prison release, prescription medication dispensation, emergency department visits, and emergency medical services).

Increased Time in Range with Ultra Rapid Lispro Treatment in Participants with Type 2 Diabetes: PRONTO-Time in Range.

Introduction: To evaluate time in range metrics and HbA1c in people with type 2 diabetes (T2D) treated with ultra rapid lispro (URLi) using continuous glucose monitoring (CGM) for the first time in this population.

Methods: This was a Phase 3b, 12-week, single-treatment study in adults with T2D on basal-bolus multiple daily injection (MDI) therapy using basal insulin glargine U-100 along with a rapid-acting insulin analog. Following a 4-week baseline period, 176 participants were newly treated with prandial URLi.

Integrated safety and efficacy analysis of dasiglucagon for the treatment of severe hypoglycaemia in individuals with type 1 diabetes.

Aims: To perform an integrated analysis of the safety and efficacy of dasiglucagon, a glucagon analogue available in a ready-to-use aqueous formulation, to treat severe hypoglycaemia (SH) in type 1 diabetes (T1D).

Materials And Methods: An integrated analysis of dasiglucagon safety was conducted on data from two placebo-controlled trials (placebo-controlled pool) and two placebo-controlled and four non-placebo-controlled trials (broad pool) in adults with T1D. An integrated analysis of dasiglucagon efficacy was conducted of pooled data and within demographic subgroups from the two placebo-controlled and two non-placebo-controlled trials in adults with T1D.

Progressive Acceleration of Insulin Exposure Over 7 Days of Infusion Set Wear.

Insulin exposure varies over 3 days of insulin infusion set (IIS) wear making day-to-day insulin dosing challenging for people with diabetes (PWD). Here we report insulin pharmacodynamic (PD) and pharmacokinetic (PK) data extending these observations to 7 days of IIS wear. PWD (A1C ≤8.

Glucagon receptor antagonist volagidemab in type 1 diabetes: a 12-week, randomized, double-blind, phase 2 trial.

Hyperglucagonemia contributes to hyperglycemia in patients with type 1 diabetes (T1D); however, novel therapeutics that block glucagon action could improve glycemic control. This phase 2 study evaluated the safety and efficacy of volagidemab, an antagonistic monoclonal glucagon receptor (GCGR) antibody, as an adjunct to insulin therapy in adults with T1D. The primary endpoint was change in daily insulin use at week 12.

Reduction in Postprandial Peak Glucose With Increased Technosphere Insulin Dosage.

Background: Technosphere Insulin (TI) is an ultra-rapid-acting inhaled insulin. This study assessed the mean peak two-hour postprandial glucose concentration with the initial TI dose (dose 1) calculated per the current label (United State Prescribing Information) compared with a ~2× higher dose (dose 2). Secondary objectives were to evaluate hypoglycemia within the two-hour postprandial period, evaluate change in forced expiratory volume in one second (FEV) before and after the two-hour postprandial period, and monitor for other adverse events.

Real-world outcomes of addition of insulin glargine 300 U/mL (Gla-300) to glucagon-like peptide-1 receptor agonist (GLP-1 RA) therapy in people with type 2 diabetes: The DELIVER-G study.

Aims: To provide real-world data on the addition of basal insulin (BI) in people with type 2 diabetes mellitus (PWD2) suboptimally controlled with glucagon-like peptide-1 receptor agonist (GLP-1RA) therapy. However, real-world data on the addition of BI to GLP-1RA therapy are limited.

Materials And Methods: We used a US electronic medical record data source (IBM® Explorys®) that includes approximately 4 million PWD2 to assess the real-world impact of adding the second-generation BI analogue insulin glargine 300 U/mL (Gla-300) to GLP-1RA therapy.

Accuracy of a Seventh-Generation Continuous Glucose Monitoring System in Children and Adolescents With Type 1 Diabetes.

Background: Accuracy of a seventh-generation "G7" continuous glucose monitoring (CGM) system was evaluated in children and adolescents with type 1 diabetes (T1D).

Methods: Sensors were worn on the upper arm and abdomen. The CGM data were available from 127 of 132 participants, ages 7 to 17 years, across 10.