Similar <scp>HbA1c</scp> reduction and hypoglycaemia with variable‐ vs fixed‐time dosing of basal insulin peglispro in type 1 diabetes: <scp>IMAGINE</scp> 7 study

Garg, Satish K.; Selam, J. L.; Bhargava, Anuj; Schloot, Nanette C.; Luo, Junxiang; Zhang, Q.; Jacobson, Jennie G.; Hoogwerf, Byron J.

doi:10.1111/dom.12740

Cited by 9 publications

(5 citation statements)

References 28 publications

(113 reference statements)

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“…There were no significant differences in severe hypoglycaemia among the three populations. Nocturnal hypoglycaemia was also reduced with morning dosing of BIL versus glargine in T1D and T2D phase II studies and nocturnal/total hypoglycaemia were similar with bedtime versus 8‐40‐hours variable‐time dosing of BIL in a T1D phase III study …”

Section: Discussionmentioning

confidence: 87%

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

Rosenstock

Marre

et al. 2016

Diabetes Obesity Metabolism

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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). BIL treatment resulted in a 36–45% lower nocturnal hypoglycaemia rate compared with glargine, despite greater reduction in glycated haemoglobin (HbA1c) and higher basal insulin dosing. The total hypoglycaemia rate was similar in patients with T2D on basal treatment only, trended towards being higher (10%) in patients with T2D on basal‐bolus treatment (p = .053), and was 15% higher (p < .001) with BIL versus glargine in patients with T1D, with more daytime hypoglycaemia in the T1D and T2D groups who were receiving basal‐bolus therapy. In T1D, during the maintenance treatment period (26‐52 weeks), the total hypoglycaemia rate was not significantly different. There were no differences in severe hypoglycaemia in the T1D or T2D pooled analyses. BIL versus glargine treatment resulted in greater HbA1c reduction with less nocturnal hypoglycaemia in all patient populations, higher daytime hypoglycaemia with basal‐bolus therapy in the T1D and T2D groups, and an associated increase in total hypoglycaemia in the patients with T1D.

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Section: Discussionmentioning

confidence: 87%

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

Rosenstock

Marre

et al. 2016

Diabetes Obesity Metabolism

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“…Morning administration of BIL, however, resulted in statistically significantly lower daytime self‐monitored blood glucose values (−0.4 to −0.6 mmol/L) at the premidday meal, pre‐evening meal and bedtime and more daytime hypoglycaemic events (a difference of ~1 event every 3 months). Flexible timing of administration of BIL was investigated in IMAGINE‐7 in patients with T1D . This cross‐over study compared 12 weeks of administration of BIL daily in the evening with 12 weeks of variable timing of administration (8‐40 hours following the last administration of BIL).…”

Section: Variable Timing Of Administration In the Imagine Trialsmentioning

confidence: 99%

“…The five trials comparing BIL with insulin glargine included two trials of basal‐bolus therapy in patients with T1D (IMAGINE‐1 and IMAGINE‐3), a basal‐bolus trial in patients with T2D (IMAGINE 4), a basal insulin trial in patients with T2D previously treated with basal insulin (IMAGINE‐5) and two trials in T2D patients who were insulin naïve, one of which compared BIL to insulin glargine (IMAGINE‐2) and the other with NPH as the comparator (IMAGINE‐6). Flexibility in the timing of administration of BIL was investigated in a trial comparing the effects on glycaemic control of bedtime administration with varying the administration interval between 8 and 40 hours in patients with T1D using a basal‐bolus regimen (IMAGINE‐7). The insulins in the T2D trials were used in combination with oral antidiabetes agents.…”

Section: Overview Of the Phase 3 Program Of Bil—the Imagine Trialsmentioning

confidence: 99%

Basal insulin peglispro: Overview of a novel long‐acting insulin with reduced peripheral effect resulting in a hepato‐preferential action

Jacober

Prince

Beals

et al. 2016

Diabetes Obesity Metabolism

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).Basal insulin peglispro (BIL) is a novel basal insulin with a flat, prolonged activity profile. BIL has been demonstrated in a dog model, in healthy men and in patients with type 1 diabetes (T1D) to have significant hepato-preferential action resulting from reduced peripheral activity. In the IMAGINE-Phase 3 clinical trial program, more than 6000 patients were included, of whom 3900 received BIL. Of the 7 pivotal IMAGINE trials, 3 studies were double-blinded and 3 were in T1D patients. BIL consistently demonstrated a greater HbA1c reduction, less glycaemic variability and a clinically relevant reduction in the rates of nocturnal hypoglycaemia across comparator [glargine and isophane insulin (NPH)] studies. Trials using basal/bolus regimens had higher rates of total hypoglycaemia with BIL due to higher rates of daytime hypoglycaemia.Severe hypoglycaemia rates were similar to comparator among both patients with T1D or type 2 diabetes (T2D). T1D patients lost weight compared with glargine (GL). Patients with T2D tended to gain less weight with BIL than with glargine. Compared to glargine, BIL was associated with higher liver fat, triglycerides and alanine aminotransferase (ALT) levels, including a higher frequency of elevation of ALT ≥3 times the upper limit of normal, but without severe, acute drug-induced liver injury. Injection site reactions, primarily lipohypertrophy, were more frequent with BIL. In conclusion, BIL demonstrated better glycaemic control with reduced glucose variability and nocturnal hypoglycaemia but higher triglycerides, ALT and liver fat relative to conventional comparator insulin. The hepato-preferential action of BIL with reduced peripheral activity may account for these findings. K E Y W O R D Sbasal insulin, drug development, drug mechanism, hypoglycaemia, insulin therapy Insulin therapy has long been a mainstay of therapy for type 1 and

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“…The IMAGINE phase 3 studies investigated basal insulin peglispro in a range of patient populations (Table ) . IMAGINE 2, 4 and 5 studied basal insulin peglispro in patients with T2DM who were insulin‐naïve, on multiple insulin injections and on basal insulin with OADs, respectively, compared with insulin glargine 100 units/mL .…”

Section: Basal Insulin In Developmentmentioning

confidence: 99%

The past, present, and future of basal insulins

Pettus

Cavaiola

Tamborlane

et al. 2015

Diabetes Metabolism Res

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Insulin production by the pancreas follows a basic pattern where basal levels of insulin are secreted during fasting periods, with prandial increases in insulin associated with food ingestion. The aim of insulin therapy in patients with diabetes is to match the endogenous pattern of insulin secretion as closely as possible without causing hypoglycaemia. There are several optimal pharmacokinetic and pharmacodynamic properties of long-acting basal insulins that can help to achieve this aim, namely, as follows: activity that is flat and as free of peaks as possible, a duration of action of ≥24-h, and as little day-to-day variation as possible. The long-acting basal insulins are a fundamental therapy for patients with type 1 and type 2 diabetes, and those that are currently available have many benefits; however, the development of even longer-acting insulins and improved insulin delivery techniques may lead to better glycemic control for patients in the future. Established long-acting basal insulins available in the United States and Europe include insulin glargine 100 units/mL and insulin detemir, both of which exhibit similar glycemic control to that of the intermediate-acting neutral protamine Hagedorn insulin, but with a reduction in hypoglycaemia. Newer insulin products available include new insulin glargine 300 units/mL (United States and Europe) and the ultra-long-acting insulin degludec (Europe) with basal insulin peglispro currently in development. These new insulins demonstrate different pharmacokinetic/pharmacodynamic profiles and longer durations of action (>24 h) compared with insulin glargine 100 units/mL, which may lead to potential benefits. The introduction of biosimilar insulins may also broaden access to insulins by reducing treatment costs. Copyright © 2015 John Wiley & Sons, Ltd.

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Similar HbA1c reduction and hypoglycaemia with variable‐ vs fixed‐time dosing of basal insulin peglispro in type 1 diabetes: IMAGINE 7 study

Cited by 9 publications

References 28 publications

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

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

Basal insulin peglispro: Overview of a novel long‐acting insulin with reduced peripheral effect resulting in a hepato‐preferential action

The past, present, and future of basal insulins

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