Once-weekly insulin efsitora alfa versus once-daily insulin degludec in adults with type 1 diabetes (QWINT-5): a phase 3 randomised non-inferiority trial.

Background: Insulin efsitora alfa (efsitora) is a once-weekly basal insulin. This phase 3 study aimed to assess the efficacy and safety of efsitora compared with insulin degludec (degludec) in adults with type 1 diabetes.

Methods: This randomised, 52-week, parallel-design, open-label, treat-to-target non-inferiority study conducted at 82 global health-care centres, randomly assigned (1:1) adults (ie, those aged ≥18 years) with type 1 diabetes glycated haemoglobin A (HbA) 7·0-10·0% (53·0-85·8 mmol/mol) to efsitora (n=343) or, degludec (n=349), both in combination with insulin lispro.

Fasting and postprandial plasma glucose contributions to hemoglobin A1c and time in range in people with diabetes on multiple daily injection insulin therapy: Results from the PRONTO-T1D and PRONTO-T2D clinical trials.

Aims: To investigate contributions of changes in fasting plasma glucose (FPG) and postprandial glucose (PPG) to changes in hemoglobin A1c (HbA1c) and time-in-range (TIR, 70-180 mg/dL) in people with type 1 diabetes (T1D) and type 2 diabetes (T2D) treated with multiple daily injections (MDI) of insulin lispro (rapid/ultra-rapid formulations).

Methods: Multivariate regression models were used to quantify the contributions of FPG and PPG reductions to change in HbA1c and TIR using data from the PRONTO-T1D (N = 1222) and PRONTO-T2D (N = 673) clinical trials. TIR was derived from 10-point self-monitored blood glucose (SMBG) profiles overall, as well as from continuous glucose monitoring (CGM) in the PRONTO-T1D CGM substudy (n = 269/1222).

Assessing Time in Range with Postprandial Glucose-Focused Titration of Ultra Rapid Lispro (URLi) in People with Type 1 Diabetes.

Introduction: To assess time in range (TIR) (70-180 mg/dL) with postprandial glucose (PPG)-focused titration of ultra rapid lispro (URLi; Lyumjev®) in combination with insulin degludec in people with type 1 diabetes (T1D).

Methods: This phase 2, single-group, open-label, exploratory study was conducted in 31 participants with T1D on multiple daily injection therapy. Participants were treated with insulin degludec and Lispro for an 11-day lead-in and then URLi for a 46-day treatment period consisting of 35-day titration and 11-day endpoint maintenance period.

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.

Efficacy and Safety of Ultra-Rapid Lispro in Younger and Older Patients with Type 2 Diabetes: Randomized Double-Blind PRONTO-T2D Study.

Introduction: Ultra-rapid lispro (URLi) is a new prandial insulin lispro formulation. In the PRONTO-T2D study, URLi, in a basal-bolus regimen with glargine or degludec, was non-inferior to lispro (Humalog) for HbA1c reduction and superior for postprandial glucose (PPG) control. We evaluated the efficacy and safety of URLi compared to lispro in younger versus older patients in PRONTO-T2D.

Decade of the dangers of multiple magnet ingestion in children: A retrospective review.

Aim: Magnet ingestion has become more frequent in children as magnetic toys and jewellery have been popularised, with the potential to cause significant morbidity. Our aim was to describe our experience at a tertiary paediatric surgical centre.

Methods: Retrospective review of patients admitted with multiple magnet ingestion (January 2011-December 2020).

Are Postoperative Intravenous Antibiotics Indicated After Laparoscopic Appendicectomy for Simple Appendicitis? A Prospective Double-blinded Randomized Controlled Trial.

Background: There is limited evidence for the use of postoperative antibiotics for simple appendicitis (SA) in children. Our aim was to conduct a prospective double-blinded randomized controlled trial to investigate this after a laparoscopic appendicectomy.

Methods: Following ethical approval, children (≤16 years) undergoing appendicectomy were recruited at a single institution.

Randomized Double-Blind Clinical Trial Comparing Ultra Rapid Lispro With Lispro in a Basal-Bolus Regimen in Patients With Type 2 Diabetes: PRONTO-T2D.

Objective: To evaluate the efficacy and safety of ultra rapid lispro (URLi) versus lispro in patients with type 2 diabetes on a basal-bolus insulin regimen.

Research Design And Methods: This was a phase 3, treat-to-target, double-blind 26-week study. After an 8-week lead-in to optimize basal insulin glargine or degludec in combination with prandial lispro treatment, patients were randomized to blinded URLi ( = 336) or lispro ( = 337) injected 0-2 min prior to meals.

Does peritoneal lavage influence the rate of complications following pediatric Laparoscopic Appendicectomy in Children with Complicated Appendicitis? A Prospective Randomized Clinical Trial.

Background: There is ongoing debate concerning the use of peritoneal irrigation in the setting of complicated appendicitis (CA) in children. Our aim was to conduct a prospective randomized controlled trial for the treatment of CA during a laparoscopic appendicectomy in children.

Methods: Following ethical approval (REC10138B), pediatric patients (≤16 years old) were recruited from a single institution over a 3-year time period (2015-2018).

Cytokeratin-18 and enhanced liver fibrosis scores in type 1 and type 2 diabetes and effects of two different insulins.

Data on cytokeratin-18 (K-18) and enhanced liver fibrosis (ELF) score in insulin-treated diabetes patients with non-alcoholic fatty liver disease (NAFLD) are limited. This study analyzed phase III data comparing basal insulin peglispro (BIL) and insulin glargine in type 1 (T1D), and type 2 diabetes (T2D) (insulin-naïve and insulin-treated). Alanine aminotransferase (ALT), K-18, ELF scores and liver fat content (LFC), measured by MRI, were obtained longitudinally.

Effects of hepato-preferential basal insulin peglispro on nuclear magnetic resonance biomarkers lipoprotein insulin resistance index and GlycA in patients with diabetes.

Aim: To characterize the effects of hepato-preferential basal insulin peglispro (BIL) and insulin glargine on insulin resistance (lipoprotein insulin resistance index [LP-IR]) and inflammation (GlycA), and to explore the biological implications.

Methods: This substudy included 847 patients with Type 1 diabetes (T1D) or Type 2 diabetes (T2D) in four cohorts of the BIL development program. LP-IR and GlycA were measured before and after insulin treatment.

Relationship of Glucose Variability With Glycated Hemoglobin and Daily Mean Glucose: A Post Hoc Analysis of Data From 5 Phase 3 Studies.

Background: The association of glucose variability (GV) with other glycemic measures is emerging as a topic of interest. The aim of this analysis is to study the correlation between GV and measures of glycemic control, such as glycated hemoglobin (HbA1c) and daily mean glucose (DMG).

Methods: Data from 5 phase 3 trials were pooled into 3 analysis groups: type 2 diabetes (T2D) treated with basal insulin only, T2D treated with basal-bolus therapy, and type 1 diabetes (T1D).

Dose Unit Establishment for a New Basal Insulin Using Joint Modeling of Insulin Dose and Glycemic Response.

Background: For new insulin analogs with properties that vary from human insulin, defining activity in units of human insulin based on glycemic lowering efficacy may be challenging. Here we present a new method that can be used to quantify a unit dose of an experimental insulin when the traditional euglycemic clamp method is not adequate.

Methods: Joint modeling of insulin dose and the glycemic outcome variable hemoglobin A1c (HbA1c), where both were response variables, was used to evaluate insulin unit potency for basal insulin peglispro (BIL).

Lipid changes during basal insulin peglispro, insulin glargine, or NPH treatment in six IMAGINE trials.

Basal insulin peglispro (BIL) is a novel basal insulin with hepato-preferential action resulting from reduced peripheral effects. This report provides an integrated summary of lipid changes at 26 weeks with BIL and comparator insulins (glargine, NPH) from phase III studies in type 1 diabetes (T1D), insulin-naïve patients with type 2 diabetes (T2D), patients with T2D on basal insulin only and patients with T2D on basal-bolus therapy. BIL treatment had little effect on HDL cholesterol and LDL cholesterol in all patients.

Reduced nocturnal hypoglycaemia with basal insulin peglispro compared with insulin glargine: pooled analyses of five randomized controlled trials.

Basal insulin peglispro (BIL) is a novel basal insulin with hepato-preferential action, resulting from reduced peripheral effects. This report summarizes hypoglycaemia data from five BIL phase III studies with insulin glargine as the comparator, including three double-blind trials. Prespecified pooled analyses (n = 4927) included: patients with type 2 diabetes (T2D) receiving basal insulin only, those with T2D on basal-bolus therapy, and those with type 1 diabetes (T1D).

Randomized Clinical Trial Comparing Basal Insulin Peglispro and Insulin Glargine in Patients With Type 2 Diabetes Previously Treated With Basal Insulin: IMAGINE 5.

Objective: To evaluate the efficacy and safety of basal insulin peglispro (BIL) versus insulin glargine in patients with type 2 diabetes (hemoglobin A1c [HbA1c] ≤9% [75 mmol/mol]) treated with basal insulin alone or with three or fewer oral antihyperglycemic medications.

Research Design And Methods: This 52-week, open-label, treat-to-target study randomized patients (mean HbA1c 7.42% [57.

Performance of an Electronic Diary System for Intensive Insulin Management in Global Diabetes Clinical Trials.

Background: This report describes the performance of a wireless electronic diary (e-diary) system for data collection and enhanced patient-investigator interactions during intensive insulin management in diabetes clinical trials.

Materials And Methods: We implemented a customized electronic communication system featuring an e-diary and a Web portal in three global, randomized, controlled Phase 3 clinical trials testing basal insulin peglispro compared with insulin glargine, both combined with prandial insulin lispro, in patients with type 1 or type 2 diabetes mellitus (T1DM and T2DM, respectively). We collected data during 28 weeks of study e-diary use for the report.

Islet autoimmunity identifies a unique pattern of impaired pancreatic beta-cell function, markedly reduced pancreatic beta cell mass and insulin resistance in clinically diagnosed type 2 diabetes.

There is a paucity of literature describing metabolic and histological data in adult-onset autoimmune diabetes. This subgroup of diabetes mellitus affects at least 5% of clinically diagnosed type 2 diabetic patients (T2DM) and it is termed Latent Autoimmune Diabetes in Adults (LADA). We evaluated indexes of insulin secretion, metabolic assessment, and pancreatic pathology in clinically diagnosed T2DM patients with and without the presence of humoral islet autoimmunity (Ab).

Comparison of safety and efficacy of insulin glargine and neutral protamine hagedorn insulin in older adults with type 2 diabetes mellitus: results from a pooled analysis.

Objectives: To compare the safety and efficacy of adding insulin glargine or neutral protamine Hagedorn (NPH) insulin to existing oral antidiabetic drug (OAD) regimens in adults with type 2 diabetes mellitus.

Design: Pooled analysis of data from five randomized controlled trials with similar designs.

Setting: Three hundred forty-two centers in more than 30 countries worldwide.

Short-term exercise improves beta-cell function and insulin resistance in older people with impaired glucose tolerance.

Background: There is a high prevalence of diabetes and impaired glucose tolerance (IGT) in the older population. Normal aging is associated with insulin resistance and impaired insulin secretion, with greater defects in people with IGT. Short-term exercise has been found to increase insulin sensitivity, but little is known about acute exercise effects on beta-cell function in older people with IGT.

Impaired beta-cell function in human aging: response to nicotinic acid-induced insulin resistance.

Context: Glucose tolerance declines with age and may involve impaired beta-cell sensitivity to glucose and beta-cell compensation for insulin resistance.

Objective: We investigated beta-cell sensitivity to glucose and beta-cell compensation for nicotinic acid-induced insulin resistance in young (age <35 yr) people with normal glucose tolerance (NGT) and old (age >60 yr) people with NGT and impaired glucose tolerance (IGT). DESIGN/PATIENTS/SETTING/INTERVENTION: Fifteen young NGT, 16 old NGT, and 14 old IGT were randomized to 2-wk treatment with nicotinic acid or placebo in a double-blind, crossover study in a university medical setting.

Limitation of the homeostasis model assessment to predict insulin resistance and beta-cell dysfunction in older people.

Context: Studies in older people have shown inconsistent agreement between homeostasis model assessment of insulin resistance (HOMA-IR) and dynamic measures of insulin action and have not evaluated HOMA beta-cell.

Objective: We compared measures of insulin sensitivity and beta-cell function from the frequently sampled iv glucose tolerance test (FSIGT) to HOMA models. DESIGN/PATIENTS/SETTING/INTERVENTION: Two hundred fourteen young and old with normal glucose tolerance (NGT) and old with impaired glucose tolerance (IGT) participated in a retrospective analysis of FSIGT data in a university medical setting.