Responses to Basal Insulin Glargine (300 U/mL and 100 U/mL) with or Without Pre-prandial Insulin in Pre-treated Subphenotypes of Type 2 Diabetes: Insights from a Post Hoc Analysis.

Introduction: This study aimed to evaluate glycemic outcomes in subphenotypes of type 2 diabetes (T2D) with HbA1c > 7.0%, previously on basal insulin (pre-BI) alone (≥ 42 U/day) or on basal-bolus therapy (pre-BB), and who were switched to either basal insulin glargine 300 U/mL (IGlar-300) or 100 U/mL (IGlar-100), with or without pre-prandial insulin.

Methods: Participants from EDITION 2 (pre-BI, n = 785), and EDITION 1 (pre-BB, n = 792) trials were assigned retrospectively to subphenotypes of T2D: severe insulin deficient diabetes (SIDD), mild age-related diabetes (MARD), mild obesity diabetes (MOD), and severe insulin resistant diabetes (SIRD).

Treatment responses to basal insulin glargine 300 U/ml and glargine 100 U/ml in newly defined subphenotypes of type 2 diabetes: A post hoc analysis of the EDITION 3 randomized clinical trial.

Introduction: To compare responses to basal insulin glargine 300 U/ml (IGlar-300) and 100 U/ml (IGlar-100) in newly defined subphenotypes of type 2 diabetes.

Methods: Insulin-naive participants (n = 858) from the EDITION 3 trial were assigned to subphenotypes 'Mild Age-Related Diabetes (MARD)', 'Mild Obesity Diabetes (MOD)', 'Severe Insulin Resistant Diabetes (SIRD)' and 'Severe Insulin Deficient Diabetes (SIDD)'. Key variables were analysed at baseline and 26 weeks.

The role of gastric emptying in glucose homeostasis and defense against hypoglycemia: Innocent bystander or partner in crime?

Maintenance of plasma glucose (PG) homeostasis is due to a complex network system. Even a minor fall in PG activates multiple neuroendocrine actions promoting hormonal, metabolic and behavioral responses, which prevent and ultimately recover hypoglycemia, primarily neuroglycopenia. Among these responses, gastric emptying (GE) plays an important role by coordinated mechanisms which regulate transit and absorption of nutrients through the small intestine.

Diurnal Cycling of Insulin Sensitivity in Type 2 Diabetes: Evidence for Deviation From Physiology at an Early Stage.

Unlabelled: The aim of this study was to establish the contribution of insulin resistance to the morning (a.m.) versus afternoon (p.

Response to insulin glargine 100 U/mL treatment in newly-defined subgroups of type 2 diabetes: Post hoc pooled analysis of insulin-naïve participants from nine randomised clinical trials.

Aims: To assess insulin glargine 100 U/mL (IGlar-100) treatment outcomes according to newly-defined subgroups of type 2 diabetes mellitus (T2DM).

Methods: Insulin-naïve T2DM participants (n = 2684) from nine randomised clinical trials initiating IGlar-100 were pooled and assigned to subgroups "Mild Age-Related Diabetes (MARD)", "Mild Obesity Diabetes (MOD)", "Severe Insulin Resistant Diabetes (SIRD)", and "Severe Insulin Deficient Diabetes (SIDD)", according to age at onset of diabetes, baseline HbA1c, BMI, and fasting C-peptide using sex-specific nearest centroid approach. HbA1c, FPG, hypoglycemia, insulin dose, and body weight were analysed at baseline and 24 weeks.

Distribution and characteristics of newly-defined subgroups of type 2 diabetes in randomised clinical trials: Post hoc cluster assignment analysis of over 12,000 study participants.

Aims: Newly-defined subgroups of type 2 diabetes mellitus (T2DM) have been reported from real-world cohorts but not in detail from randomised clinical trials (RCTs).

Methods: T2DM participants, uncontrolled on different pre-study therapies (n = 12.738; 82 % Caucasian; 44 % with diabetes duration > 10 years) from 14 RCTs, were assigned to new subgroups according to age at onset of diabetes, HbA1c, BMI, and fasting C-peptide using the nearest centroid approach.

Insulin: evolution of insulin formulations and their application in clinical practice over 100 years.

The first preparation of insulin extracted from a pancreas and made suitable for use in humans after purification was achieved 100 years ago in Toronto, an epoch-making achievement, which has ultimately provided a life-giving treatment for millions of people worldwide. The earliest animal-derived formulations were short-acting and contained many impurities that caused adverse reactions, thereby limiting their therapeutic potential. However, since then, insulin production and purification improved with enhanced technologies, along with a full understanding of the insulin molecule structure.

One-hundred year evolution of prandial insulin preparations: From animal pancreas extracts to rapid-acting analogs.

The first insulin preparation injected in humans in 1922 was short-acting, extracted from animal pancreas, contaminated by impurities. Ever since the insulin extracted from animal pancreas has been continuously purified, until an unlimited synthesis of regular human insulin (RHI) became possible in the '80s using the recombinant-DNA (rDNA) technique. The rDNA technique then led to the designer insulins (analogs) in the early '90s.

Insulin Centennial: Milestones influencing the development of insulin preparations since 1922.

During 1921 to 1922, a team effort by Banting, Macleod, Collip and Best isolated and purified insulin and demonstrated its life-giving properties, giving rise to the birth of insulin therapy. In the early years (1922-1950), priorities revolved around the manufacture of insulin to meet demand, improving purity to avoid allergic reactions, establishing insulin standards and increasing its duration of action to avoid multiple daily injections. Shortly after the emergence of insulin, Joslin and Allen advocated the need to achieve and maintain good glycaemic control to realize its full potential.

The physiological basis of insulin therapy in people with diabetes mellitus.

Insulin therapy has been in use now for 100 years, but only recently insulin replacement has been based on physiology. The pancreas secretes insulin at continuously variable rates, finely regulated by sensitive arterial glucose sensing. Pancreatic insulin is delivered directlyin the portal blood to insulinize preferentially the liver.

Glycaemic control and hypoglycaemia risk with insulin glargine 300 U/mL and insulin degludec 100 U/mL in older participants in the BRIGHT trial.

Aim: To evaluate the efficacy and safety of insulin glargine 300 U/mL (Gla-300) versus insulin degludec 100 U/mL (IDeg-100) in predefined (
Materials And Methods: BRIGHT was the first head-to-head randomized trial comparing Gla-300 and Deg-100 in insulin-naïve adults with T2D. In this subanalysis, endpoints were studied by predefined ( View Article and Find Full Text PDF

Pharmacokinetic and Pharmacodynamic Head-to-Head Comparison of Clinical, Equivalent Doses of Insulin Glargine 300 units · mL and Insulin Degludec 100 units · mL in Type 1 Diabetes.

Objective: To prove equivalence of individual, clinically titrated basal insulin doses of glargine 300 units ⋅ mL (Gla-300) and degludec 100 units ⋅ mL (Deg-100) under steady state conditions in a single-blind, randomized, crossover study, on the glucose pharmacodynamics (PD) in people with type 1 diabetes (T1D).

Research Design And Methods: Subjects with T1D ( = 22, 11 men, age 44.3 ± 12.

Equipotency of insulin glargine 300 and 100 U/mL with intravenous dosing but differential bioavailability with subcutaneous dosing in dogs.

Aims: Insulin glargine 300 U/mL (Gla-300) contains the same units versus glargine 100 U/mL (Gla-100) in three-fold lower volume, and higher subcutaneous (SC) doses are required in people with diabetes. To investigate blood glucose (BG) lowering potency, Gla-300 and Gla-100 were compared after intravenous (IV, for 4 h) and SC (for 24 h) injection in healthy Beagle dogs.

Materials And Methods: The dose of 0.

Lower risk of severe hypoglycaemia with insulin glargine 300 U/mL versus glargine 100 U/mL in participants with type 1 diabetes: A meta-analysis of 6-month phase 3 clinical trials.

Severe hypoglycaemia (SH) remains a challenge to people with type 1 diabetes (T1DM), and new-generation basal insulins may improve patient outcomes. This post hoc meta-analysis explored the risk of SH with insulin glargine 300 U/mL (Gla-300) versus glargine 100 U/mL (Gla-100) in a pooled population with T1DM from three randomized, multicentre, 6-month similarly designed phase 3 trials: EDITION 4, EDITION JP 1 and EDITION JUNIOR. Endpoints included incidence and time to first occurrence of SH.

Hypoglycaemia risk with insulin glargine 300 U/mL compared with glargine 100 U/mL across different baseline fasting C-peptide levels in insulin-naïve people with type 2 diabetes: A post hoc analysis of the EDITION 3 trial.

The relationship between baseline fasting C-peptide (FCP) and glucose control was examined in insulin-naïve people with type 2 diabetes inadequately controlled with oral antihyperglycaemic drugs commencing basal insulin glargine 300 U/mL (Gla-300) or 100 U/mL (Gla-100) in the absence of sulfonylurea/glinides. Participants with FCP measurement from the EDITION 3 trial (n = 867) were stratified according to baseline FCP (≤0.40, >0.

Differential glycaemic control with basal insulin glargine 300 U/mL versus degludec 100 U/mL according to kidney function in type 2 diabetes: A subanalysis from the BRIGHT trial.

Aims: Chronic kidney disease (CKD) challenges diabetes management and is associated with increased cardiovascular morbidity and mortality. We examined whether clinical outcomes with insulin glargine 300 U/mL (Gla-300) and insulin degludec 100 U/mL (IDeg-100) are affected by renal function in a prespecified subgroup analysis from the BRIGHT trial.

Materials And Methods: BRIGHT (NCT02738151) was a multicentre, open-label, randomized, active-controlled, two-arm, parallel-group, 24-week study in insulin-naïve uncontrolled type 2 diabetes (T2D).

Comparable efficacy with similarly low risk of hypoglycaemia in patient- vs physician-managed basal insulin initiation and titration in insulin-naïve type 2 diabetic subjects: The Italian Titration Approach Study.

Aims: People with uncontrolled type 2 diabetes (T2DM) often delay initiating and titrating basal insulin. Patient-managed titration may reduce such deferral. The Italian Titration Approach Study (ITAS) compared the efficacy and safety of insulin glargine 300 U/mL (Gla-300) initiation and titration using patient- (nurse-supported) or physician-management in insulin-naïve patients with uncontrolled T2DM.

The continuing quest for better subcutaneously administered prandial insulins: a review of recent developments and potential clinical implications.

The class of rapid-acting insulin analogues were introduced more than 20 years ago to control postprandial plasma glucose (PPG) excursions better than unmodified regular human insulin. Insulins, lispro, aspart and glulisine all achieved an earlier onset of action, greater peak effect and shorter duration of action resulting in lower PPG levels and a reduced risk of late postprandial hypoglycaemia. However, the subcutaneous absorption rate of these analogues still fails to match the physiological profile of insulin in the systemic circulation following a meal.

Fasting C-peptide, a biomarker for hypoglycaemia risk in insulin-naïve people with type 2 diabetes initiating basal insulin glargine 100 U/mL.

Aim: To examine the relationship between baseline fasting C-peptide (FCP) and outcomes in insulin-naïve people with type 2 diabetes initiating basal insulin glargine 100 U/mL (Gla-100).

Materials And Methods: Post hoc pooled analysis of nine randomized, treat-to-target trials in patients with type 2 diabetes inadequately controlled on oral antihyperglycaemic drugs initiating once-daily Gla-100. Participants (n = 2165) were stratified at baseline according to FCP (≤0.

Greater Suppression of Glucagon, Lipolysis, and Ketogenesis with Insulin Glargine U300 as Compared with Glargine U100 in Type 1 Diabetes Mellitus.

The aim of this study was to establish the effects of clinical doses of Gla-300 versus Gla-100 on suppression of glucagon, lipolysis, and ketogenesis in type 1 diabetes mellitus (T1DM). Eighteen persons with T1DM (age 40 ± 12 years, diabetes duration 26 ± 12 years, body mass index 23.4 ± 2 kg/m, A1C 7.