scholarly journals Basal Insulin Peglispro Demonstrates Preferential Hepatic Versus Peripheral Action Relative to Insulin Glargine in Healthy Subjects

Diabetes Care ◽  
2014 ◽  
Vol 37 (9) ◽  
pp. 2609-2615 ◽  
Author(s):  
Robert R. Henry ◽  
Sunder Mudaliar ◽  
Theodore P. Ciaraldi ◽  
Debra A. Armstrong ◽  
Paivi Burke ◽  
...  
Keyword(s):  
Insulin Glargine ◽  
Basal Insulin ◽  
Healthy Subjects ◽  
Peripheral Action

scholarly journals Basal Insulin Fc (BIF), A Novel Insulin Suited For Once Weekly Dosing For The Treatment of Patients With Diabetes Mellitus

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A329-A329
Author(s):  
Tim Heise ◽  
Jenny Chien ◽  
John Beals ◽  
Charles Benson ◽  
Oliver Klein ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Steady State ◽  
Insulin Glargine ◽  
Half Life ◽  
Basal Insulin ◽  
Healthy Subjects ◽  
Loading Dose ◽  
The Mean ◽  
Flat Profile ◽  
Dose Levels

Abstract An optimally designed once-weekly basal insulin with reduced day-to-day pharmacokinetic (PK)/pharmacodynamic (PD) fluctuations compared to daily basal insulins should have a low peak-to-trough ratio at steady state. An insulin with this flat profile could improve glycemic efficacy while reducing hypoglycemia. Basal insulin Fc (BIF; LY3209590) is an insulin IgG Fc-fusion protein developed for once weekly dosing. The results of the first in-human studies of BIF assessing the safety, tolerability, PK, and PD following single and once-weekly doses of BIF are presented below. The single ascending dose (SAD) study assessed 6 dose levels of BIF, administered to healthy subjects or patients with type 2 diabetes mellitus (T2DM). In the multiple ascending dose (MAD) study, patients with T2DM previously treated with basal insulin received a one-time loading dose at Week 1 followed by a once-weekly maintenance dose for 5 additional weeks. Four fixed-dose maintenance dose levels were evaluated. The loading dose was implemented to rapidly achieve steady-state BIF concentration at each dose level. Patients with T2DM in the control group received insulin glargine at the same dose as their previous daily insulin dose. Key objectives were safety and tolerability, PK endpoints with a focus on half-life and peak-to-trough ratio at steady state, and finally PD measures. The SAD study included 57 patients with T2DM and 16 healthy subjects. The mean age of patients with T2DM was 58.4 years and the mean BMI was 29.5±3.2 kg/m2. The mean age of healthy subjects was 35.8±9.3 years and the mean BMI was 26.1±3.1 kg/m2. In the SAD study, BIF demonstrated linear PK with dose-proportional concentration profiles in healthy subjects and patients with T2DM. The maximum BIF concentration was reached on Day 4. BIF had a mean half-life of approximately 17 days in patients with T2DM. Following a single dose of BIF, a decrease in FBG was observed on Day 1 and was sustained until at least 5 days post-dose. In the MAD study in 33 subjects with T2DM aged between 40 and 69 years, BIF demonstrated a nearly peak-less PK profile over a one-week dosing interval with a peak-to-trough ratio of ~1.1 at steady state. This flat profile is in contrast to insulin glargine. Following once-daily dosing, insulin glargine has a daily peak-to-trough ratio of ~2. Over the 6-week duration, the 7-point glucose profiles remained constant over time and were similar to insulin glargine profiles. BIF was well tolerated and had a safety profile similar to insulin glargine-treated subjects. In particular, hypoglycemia rates were also similar to insulin glargine and there was no occurrence of hypoglycemic events with cognitive dysfunction. These data support continued development of BIF as a once-weekly insulin treatment of diabetes mellitus.

Switching to Insulin Glargine 300 U/mL (Gla-300) Improves Glycemic Control and Reduces Nocturnal Hypoglycemia in Patients (Pts) with Type 2 Diabetes (T2DM) on Basal Insulin Supported Oral Therapy (BOT)

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 1020-P ◽  
Author(s):  
JOCHEN SEUFERT ◽  
ANDREAS FRITSCHE ◽  
HELMUT ANDERTEN ◽  
KATRIN PEGELOW ◽  
STEFAN PSCHERER ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Glycemic Control ◽  
Insulin Glargine ◽  
Basal Insulin ◽  
Oral Therapy ◽  
Nocturnal Hypoglycemia

scholarly journals A Randomized Trial of Insulin Glargine plus Oral Hypoglycemic Agents versus Continuous Subcutaneous Insulin Infusion to Treat Newly Diagnosed Type 2 Diabetes

2018 ◽  
Vol 2018 ◽  
pp. 1-9
Author(s):  
Shuo Lin ◽  
Mu Chen ◽  
Wanling Chen ◽  
Keyi Lin ◽  
Panwei Mu ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Glycemic Control ◽  
Insulin Glargine ◽  
Basal Insulin ◽  
Insulin Infusion ◽  
Cell Function ◽  
Hypoglycemic Agents ◽  
Newly Diagnosed ◽  
Oral Hypoglycemic Agents

Aims. Basal insulin plus oral hypoglycemic agents (OHAs) has not been investigated for early intensive antihyperglycemic treatment in people with newly diagnosed type 2 diabetes. This study is aimed at comparing the short-term (over a period of 12 days) effects of basal insulin glargine plus OHAs and continuous subcutaneous insulin infusion (CSII) on glycemic control and beta-cell function in this setting. Methods. An open-label parallel-group study. Newly diagnosed hospitalized patients with type 2 diabetes and fasting plasma glucose (FPG) ≥11.1 mmol/L or glycated hemoglobin (HbA1c) ≥9% (75 mmol/mol) were randomized to CSII or insulin glargine in combination with metformin and gliclazide. The primary outcome measure was the mean amplitude of glycemic excursions (MAGE), and secondary endpoints included time to reach glycemic control target (FPG < 7 mmol/L and 2-hour postprandial plasma glucose < 10 mmol/L), markers of β-cell function, and hypoglycemia. Results. Subjects in the CSII (n=35) and basal insulin plus OHA (n=33) groups had a similar significant reduction from baseline to end of treatment in glycated albumin (−6.44 ± 3.23% and− 6.42 ± 3.56%, P=0.970). Groups A and B have comparable time to glycemic control (3.6 ± 1.2 days and 4.0 ± 1.4 days), MAGE (3.40 ± 1.40 mmol/L vs. 3.16 ± 1.38 mmol/L; p=0.484), and 24-hour mean blood glucose (7.49 ± 0.96 mmol/L vs. 7.02 ± 1.03 mmol/L). Changes in the C-peptide reactivity index, the secretory unit of islet in transplantation index, and insulin secretion-sensitivity index-2 indicated a greater β-cell function improvement with basal insulin plus OHAs versus CSII. Conclusions. Short-term insulin glargine plus OHAs may be an alternative to CSII for initial intensive therapy in people with newly diagnosed type 2 diabetes.

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