Philip D Home

• Newcastle University

Aims To estimate the relative treatment effect of iGlarLixi (a fixed‐ratio combination of insulin glargine 100 U/mL plus lixisenatide) versus premixed insulin IDegAsp (insulin degludec plus insulin aspart) in people with type 2 diabetes (T2D) who advanced from basal insulin to iGlarLixi or IDegAsp in non‐Asian studies. Materials and Methods Random...

Aims To explore details of the incidence and rates of daytime and nocturnal hypoglycaemia, levels of hypoglycaemia, and relationship to glycated haemoglobin (HbA1c), when comparing iGlarLixi versus premixed biphasic insulin aspart 30 (BIAsp 30) in the SoliMix randomized controlled trial. Materials and Methods This exploratory analysis of SoliMix u...

Introduction: SoliMix (EudraCT: 2017-003370-13) found better HbA1c, weight benefit, and lower hypoglycemia risk with iGlarLixi vs. premix BIAsp 30 in people with type 2 diabetes (T2D) advancing from basal insulin (BI) + oral antihyperglycemic drugs (OADs) . Methods: Adults with T2D and HbA1c 7.5-10.0 % on BI + 1-2 OADs were randomized to once-daily...

Introduction: SoliMix (EudraCT: 2017-003370-13) found better HbA1c, weight benefit, and lower hypoglycemia risk requiring less insulin with once-daily iGlarLixi vs. twice-daily premix BIAsp 30 in people with type 2 diabetes (T2D) advancing from basal insulin (BI) and oral antihyperglycemic drugs (OADs) . Methods: Adults with T2D and HbA1c 7.5-% on...

Insulin therapy has a long history at the cutting edge of technological development through purification, extended-action, molecular chemistry, and devices, and in support technologies including self-measurement and patient education. But unmet needs remain large. Today's therapy cannot deliver minute-to-minute control of glucose levels, and cannot...

Aim To assess the efficacy and safety of iGlarLixi, a fixed‐ratio combination of insulin glargine 100 U/mL and lixisenatide, relative to premix insulin and other insulin options through network meta‐analysis. Methods A systematic literature search identified randomized controlled trials (RCTs) comparing iGlarLixi, premix insulin or basal insulin (...

Objective: The principle of replacing prandial insulin lispro with a once-weekly glucagon-like peptide 1 receptor agonist (GLP-1RA) for type 2 diabetes inadequately controlled on a multiple daily insulin injections regimen was tested with albiglutide. Research design and methods: In this treat-to-target study, basal plus prandial insulin was opt...

In people with type 2 diabetes uncontrolled by GLP-1 RAs, fixed-ratio combination (FRC; basal insulin + GLP-1 RA) is a recommended option. A PICO-framework systematic review of RCTs followed by an ITC was performed to compare the efficacy and safety of the FRCs iGlarLixi (insulin glargine 100 U/mL + lixisenatide) and IDegLira (insulin degludec + li...

Glycated hemoglobin targets have been given in guidelines for the last three decades, mostly without change at around 6.5-7.0% (47-53 mmol/mol). Personalization of such targets has also long been advocated, but often with little and inappropriate guidance. More recently some have suggested higher targets might be indicated, and more specifically lo...

Pooled participant-level data from 16 RCTs (≥ 24 weeks) were used to explore the association of demographic and clinical markers with different levels of HbA1c achieved at Week 24 in insulin-naive people with T2DM on oral agents after starting insulin glargine 100 U/mL (Gla-100). A stepwise logistic regression analysis was performed to identify pot...

The glycemic efficacy of weekly Albi 50 mg to replace prandial insulin lispro (Lis) was evaluated in T2DM inadequately controlled on a multiple daily insulin regimen (≥3 injections/day). Basal/bolus insulin was optimized during a 4 week run-in phase before randomization to: 1) Albi + optimized insulin glargine (Gla), with prandial Lis subsequently...

TABLE S1. Total daily insulin dose and achieved HbA1c in the populations using different insulin regimens at year 1 and at year 4.

Aim: To identify factors associated with documented symptomatic and severe hypoglycaemia over 4 years in people with type 2 diabetes starting insulin therapy. Materials and methods: CREDIT, a prospective international observational study, collected data over 4 years on people starting any insulin in 314 centers; 2729 and 2271 people had hypoglyc...

Aims: A number of insulin regimens are used in type 2 diabetes. This analysis aims to better understand the evolution of insulin therapy in different regions of Europe. Methods: Data from people starting any insulin were collected in eastern Europe (EEur: Croatia, Russia, Ukraine), northern Europe (NEur: Finland, Germany, UK) and southern Europe...

Aims: Insulin glargine 300 U/mL (Gla-300) offers a flatter pharmacodynamic profile than insulin glargine 100 U/mL (Gla-100). We have compared these insulins over 1 year in people with type 1 diabetes (T1DM). Methods: EDITION 4 was a 6-month, multicentre, randomized, open-label phase 3 study. People with T1DM completing the 6 months continued the...

Aim: To explore if efficacy and safety findings for insulin glargine 300U/mL (Gla-300) versus insulin glargine 100U/mL (Gla-100), observed over 6 months in insulin-naïve people with type 2 diabetes, are maintained after 12 months. Methods: EDITION 3 was a phase 3a, randomized, multicentre, open-label, parallel-group, treat-to-target study of onc...

Aims Diabetes therapies that provide durable glycaemic control for people with type 2 diabetes mellitus (T2DM) are needed. We present efficacy results of albiglutide, a glucagon-like peptide-1 receptor agonist, in people with T2DM over a 3-year period. Methods Five of the 8 HARMONY phase 3 trials, comparing albiglutide with other therapies or plac...

Thanks to significant improvements in the precision, accuracy, and usability of continuous glucose monitoring (CGM), its relevance in both ambulatory diabetes care and clinical research is increasing. In this study, we address the latter perspective and derive provisional reporting recommendations. CGM systems have been available since around the y...

Pathak et al. (1) record severe hypoglycemic events in “emergency department or inpatient medical encounters” and comment that they were “likely to have included some cases … that occurred as a consequence of treatment initiated after hospitalization.” The event rates they note are very high compared with reports from studies in ambulatory care. Is...

GLP-1 receptor agonist; insulin therapy; meta-analysis

The overall impact of glucose lowering on vascular complications and major clinical outcomes, including mortality, in type 2 diabetes is still an open issue. While intensive glucose control has undoubted benefit for microvascular end points, the relationship between glucose-lowering approaches and reduced incidence and/or progression of macrovascul...

Aims: To provide a review of the available data and practical use of IDegAsp. Premixed insulins provide basal and prandial glucose control; however, they have an intermediate-acting prandial insulin component and do not provide as effective basal coverage as true long-acting insulins, owing to the physicochemical incompatibility of their individua...

Introduction L'analyse poolee des etudes EDITION 1, 2 et 3 (sur 6 mois), a montre que l'insuline glargine 300 U/mL (Gla-300) provoquait moins d'hypoglycemies confirmees ou severes (soit nocturnes, de 00 h 00 a 05 h 59, soit sur l'ensemble des 24 h) que l'insuline glargine 100 U/mL (Gla-100) chez des patients DT2. Cependant, cette fenetre nocturne t...

Background: Insulin glargine 300 U/mL (Gla-300) has a more constant and prolonged action profile than insulin glargine 100 U/mL and in clinical studies is associated with similar glycemic control but less hypoglycemia. Whether its effects are altered by variability of injection time was examined in two 3-month substudies. Materials and methods:...

The co-formulation insulin degludec/insulin aspart (IDegAsp) contains insulin degludec (IDeg), a basal insulin, and the rapid-acting insulin aspart (IAsp). Its unique pharmacodynamic profile provides a stable basal insulin action over a 24-h period due to the flat, ultra-long effect of IDeg, combined with prandial control from IAsp, which is unaffe...

The euglycemic glucose clamp was first used to assess the new human insulins in the early 1980s by comparing pharmacodynamics (PD) of square-wave intravenous infusions in terms of the clamp glucose infusion rate (1). Shortly afterward, the technique was adapted to study the profile of action of subcutaneously injected insulin (2) and in people with...

Aims: CREDIT (Cardiovascular Risk Evaluation in people with Type 2 Diabetes on Insulin Therapy) was a non-interventional study designed to examine relationships between glycated haemoglobin (HbA1c) and cardiovascular (CV) events in people beginning insulin in routine clinical practice in Europe, North America and Asia. Materials and methods: Dat...

SMBG is widely used in clinical trials. Researchers recognize the importance of documenting glycemic variability, postprandial glucose excursions, and symptomatic and asymptomatic hypoglycemic episodes in their study participants. Furthermore, SMBG data are often used in clinical trials to guide the prescription and dosage of diabetes medications a...

As obesity rates increase, so too do the risks of type 2 diabetes, cardiovascular disease, and numerous other detrimental conditions. The prevalence of obesity in U.S. adults more than doubled between 1980 and 2010, from 15.0 to 36.1%. Although this trend may be leveling off, obesity and its individual, societal, and economic costs remain of grave...

Insulin therapy in type 1 diabetes still provides suboptimal outcomes. Insulin glargine 300 units/mL (Gla-300), with a flatter pharmacodynamic profile compared with insulin glargine 100 units/mL (Gla-100), is an approach to this problem. People with type 1 diabetes, using a mealtime and basal insulin regimen, were randomized open-label to Gla-300 o...

Many people with diabetes rely on insulin therapy to achieve optimal blood glucose control. A fundamental aim of such therapy is to mimic the pattern of 'normal' physiological insulin secretion, thereby controlling basal and meal-time plasma glucose and fatty acid turnover. In people without diabetes, insulin release is modulated on a time base of...

Biosimilar insulins are approved copies of insulins outside patent protection. Advantages may include greater market competition and potential cost reduction, but clinicians and users lack a clear perspective of "biosimilarity" for insulins. The manufacturing processes for biosimilar insulins are manufacturer-specific and, although reviewed by regu...

Hintergrund und Ziele: Insulin glargin (300 E/ml; U300) weist ein im Vergleich zu Insulin glargin 100 E/ml (U100) noch gleichmasigeres und uber 24h hinaus anhaltendes PK/PD-Profil auf. Der Einfluss von flexiblen Injektionsintervallen (24h ± bis zu 3h) an min. 2 Tagen/Woche auf die Stoffwechselkontrolle wurde bei U300 behandelten Typ-2-Diabetes-Pati...

AimsTo evaluate maintenance of efficacy and safety of insulin glargine 300 U/mL (Gla-300) versus glargine 100 U/mL (Gla-100) in people with type 2 diabetes mellitus using basal plus meal-time insulin for 12 months in EDITION 1.Materials and methodsEDITION 1 was a multicentre, randomized, open-label, two-arm, phase 3a study. Participants completing...

Objectif Évaluer la relation entre événements cardiovasculaires (CV) et HbA1c chez des patients DT2 ayant débuté une insulinothérapie « en vie réelle » (étude Cardiovascular Risk Évaluation in people with Type 2 Diabetes on Insulin Therapy, CREDIT). Les données étant recueillies à partir des rapports des médecins. Patients et méthodes 2 999 patien...

Insulin analog patent expiry is likely to mean that, increasingly, copies of original biopharmaceutical products will be submitted for authorization. Experience with biosimilars in other therapeutic areas suggests that careful regulation and caution are needed. Published guidelines of regulatory authorities around the world on approval of biosimila...

To identify factors associated with glucose control, as measured by HbA1c over 4 years, in people with type 2 diabetes starting insulin therapy. CREDIT, an observational cohort study, collected data semi-annually over 4 years, on people with type 2 diabetes starting any insulin, in 311 centres in 12 countries; 2803 people had data on HbA1c during f...

Rationnel La nouvelle insuline glargine 300 U/ml (Gla-300) présente un profil pharmacocinétique et pharmacodynamique plus prolongé et plus plat que l’insuline glargine 100 U/ml (Gla-100). EDITION 3 a comparé l’efficacité et la tolérance des deux formulations chez des patients DT2, naïfs d’insuline, en échec de traitement par hypoglycémiants non ins...

Rationnel L’un des facteurs susceptibles de retarder la mise sous insuline de patients DT2 est la conviction qu’une prise de poids puisse influencer négativement le contrôle glycémique. Nous avons donc évalué cette éventuelle relation après 4 ans d’insulinothérapie dans la pratique clinique courante. Patients et méthodes CREDIT est une étude non i...

Objectif La nouvelle insuline glargine 300 U/ml (Gla-300) présente un profil pharmacocinétique et pharmacodynamique plus prolongé et plus plat que l’insuline glargine 100 U/ml (Gla-100). Cette étude de phase 3a (EDITION 1) a comparé l’efficacité et la tolérance des deux formulations chez des patients diabétiques de type 2 (DT2) sous schéma basal-bo...

Objectif Comparer efficacité et sécurité de la nouvelle insuline glargine 300 U/ ml (Gla-300) vs glargine 100 U/ml (Gla-100) chez des patients avec diabète de type 1 (DT1). Patients et méthodes Étude multicentrique, multinationale, en ouvert, à 6 mois. 549 patients DT1 (IMC = 27,6 kg/m², ancienneté = 21,0 années, HbA1c = 8,1 %) ont été randomisés...

Rationnel Le profil pharmacocinétique et pharmacodynamique plus prolongé au-delà de 24 heures et plus plat de la nouvelle insuline glargine 300 U/ml (Gla-300) offre un rationnel pour une flexibilité d’injection de la dose quotidienne en fonction du mode de vie des patients. Nous avons comparé l’efficacité et la tolérance d’administration d’insuline...

Hypoglycaemic events (% participants affected) for Gla-300 versus Gla-100 during 6 months of treatment, by intervals of time of day (safety population).

Further details of statistical analyses.

List of investigators.

Eight-point self-monitored plasma glucose (SMPG) profile at baseline and at the end of treatment (modified intention-to-treat population).

Assessment of treatment satisfaction using the Diabetes Treatment Satisfaction Questionnaire (status version, DTSQs) (modified intention-to-treat population).

Participant flow diagram.

Cumulative mean numbers of confirmed (plasma glucose ≤3.9 mmol/l) or severe hypoglycaemic events per participant during the main 6-month treatment period (safety population).

Hypoglycaemic events and event rates (per participant-year of exposure) for Gla-300 versus Gla-100 during 6 months of treatment, by intervals of time of day (safety population).

Treatment-emergent serious adverse events (safety population).

It is of interest to understand how insulin therapy currently evolves in clinical practice, in the years after starting insulin in people with type 2 diabetes. We aimed to describe this evolution prospectively over 4 years, to assist health care planning. People who had started any insulin were identified from 12 countries on three continents. Base...

AimsTo compare efficacy and safety of new insulin glargine 300 U/mL (Gla-300) with glargine 100 U/mL (Gla-100) in insulin-naïve people with type 2 diabetes using oral glucose-lowering drugs.MethodsEDITION 3 was a multicenter, open-label, parallel-group study. Participants were randomized to Gla-300 or Gla-100 once daily for 6 months, discontinuing...

The RECORD study evaluated the effects of rosiglitazone on cardiovascular outcomes. A 4-year observational follow-up was added to the study to monitor the occurrence of cancer and bone fractures. We present the cancer and bone fracture data aggregated across the main study and its observational follow-up. RECORD was a multicentre, open-label trial...

We very much concur with Nick Finer that weight is not everything (1). Finer argues that changes in body composition and not just change in weight are important, and he concludes that in any case, the benefits of insulin therapy on metabolic control must be balanced against penalties from weight gain. The improvement seen in HbA1c after treatment...

Maintenance of endogenous pancreatic β-cell function could be an important goal in the management of type 1 diabetes. However, the impact of stimulated C-peptide level on overall glycemic control is unknown. The relationship between C-peptide and parameters of glucose control was therefore characterized in a cohort with rapidly changing β-cell func...

Aims: There is limited evidence with respect to the cost-effectiveness of starting insulin in people with diabetes outside the 'western' world. The aim of this study was to assess the cost-effectiveness of starting basal insulin treatment with insulin detemir in people with type 2 diabetes (T2D) inadequately controlled on oral glucose-lowering dru...

We have read the article recently published by Home et al. (1). This report conveys an important perspective on insulin therapy in patients with type 2 diabetes by a working party of diabetes specialists and comments on optimal insulin management of individuals with this condition. The purpose of this group was to summarize the current published da...

AimsThis study investigated the efficacy and tolerability of albiglutide, a weekly glucagon-like peptide-1 receptor agonist, when used in a triple therapy regimen added to metformin and glimepiride in people with type 2 diabetes mellitus.Methods This was a 156-week, randomized, double-blind, parallel-group, multicenter study; described here are the...

A1chieve was a 24-week, non-interventional study evaluating safety and effectiveness of an insulin analog (detemir, aspart, biphasic insulin aspart 30) in 66 726 people with type 2 diabetes in 28 countries. The present analysis addressed safety and effectiveness in insulin-naïve groups with diabetes duration 15 years.

Aim This study aimed to assess the cost-effectiveness of starting insulin therapy with biphasic insulin aspart 30 (BIAsp 30) in people with type 2 diabetes inadequately controlled on oral glucose-lowering drugs in Saudi Arabia, India, Indonesia, and Algeria. Methods The IMS CORE Diabetes Model was used to evaluate economic outcomes associated with...

The trend toward personalized management of diabetes has focused attention on the differences among available pharmacological agents in terms of mechanisms of action, efficacy, and, most important, safety. Clinicians must select from these features to develop individualized therapy regimens. In June 2013, a nine-member Diabetes Care Editors' Expert...

We read with interest the results of the A1chieve study (1), a noninterventional, observational, 24-week study examining the safety and effectiveness of insulin analogs (detemir, aspart, biphasic aspart 30 [all Novo Nordisk, Bagsvaerd, Denmark]) alone or in combination in routine clinical use in 66,726 people with type 2 diabetes. The mean change i...

Objective: To compare the efficacy and safety of new insulin glargine 300 units/mL (Gla-300) with glargine 100 units/mL (Gla-100) in people with type 2 diabetes on basal insulin (≥42 units/day) plus mealtime insulin. Research design and methods: EDITION 1 (NCT01499082) was a 6-month, multinational, open-label, parallel-group study. Adults with g...

Figure S1. Participant disposition.

Figure S2. Eight-point PG profiles at baseline and end of treatment for insulin glargine and NPH insulin.

Table S1. Summary of patients screened and randomly assigned, overall and by country – all screened patients.

Given the continued interest in defining the optimal management of individuals with type 2 diabetes, the Editor of Diabetes Care convened a working party of diabetes specialists to examine this topic in the context of insulin therapy. This was prompted by recent new evidence on the use of insulin in such people. The group was aware of evidence that...

AimsInsulin glargine causes less nocturnal hypoglycaemia than human NPH insulin in treat-to-target studies in insulin-naïve people with type 2 diabetes. The present study examined whether this clinical benefit can lead to superior control of HbA1c with glargine, using a protocol designed to limit nocturnal hypoglycaemia.MethodsLANCELOT was a 36-wee...

The availability of biosimilar insulins can potentially lead to lower insulin costs and increased access for patients with diabetes, worldwide. However, clinicians and regulatory agencies have raised several concerns regarding the safety and efficacy of these new medications. The European regulatory agencies have established guidelines for market a...

Objective: Moderate weight gain is usual after starting insulin therapy. The identification and quantification of factors associated with weight gain may help target strategies for avoidance of weight gain. Research design and methods: The noninterventional CREDIT (Cardiovascular Risk Evaluation in people with type 2 Diabetes on Insulin Therapy)...

OBJECTIVE Individualization of therapy choices requires the prediction of likely response. Predictor and explanatory factors of change in HbA1c were studied using data from a large observational study of starting insulin analog therapy (the A1chieve study).RESEARCH DESIGN AND METHODS Univariate analyses were performed for insulin-naive people and p...

Objectif Chez les patients DT2 ayant débuté un traitement par insuline, plusieurs schémas d’insulinothérapie sont utilisés. Ces schémas, leur évolution et les résultats sur quatre ans sont décrits ici. Patients et méthodes L’étude CREDIT a été menée dans 12 pays sur 3 continents. Les données recueillies à la mise sous insuline étaient rétrospectiv...