Patient‐level meta‐analysis of the EDITION 1, 2 and 3 studies: glycaemic control and hypoglycaemia with new insulin glargine 300 U/ml versus glargine 100 U/ml in people with type 2 diabetes

Abstract

AimsTo conduct a patient-level meta-analysis of the EDITION 1, 2 and 3 studies, which compared the efficacy and safety of new insulin glargine 300 U/ml (Gla-300) with insulin glargine 100 U/ml (Gla-100) in people with type 2 diabetes (T2DM) on basal and mealtime insulin, basal insulin and oral antihyperglycaemic drugs, or no prior insulin, respectively.MethodsThe EDITION studies were multicentre, randomized, open-label, parallel-group, phase IIIa studies, with similar designs and endpoints. A patient-level meta-analysis of the studies enabled these endpoints to be examined over 6 months in a large population with T2DM (Gla-300, n = 1247; Gla-100, n = 1249).ResultsNo significant study-by-treatment interactions across studies were found, enabling them to be pooled. The mean change in glycated haemoglobin was comparable for Gla-300 and Gla-100 [each −1.02 (standard error 0.03)%; least squares (LS) mean difference 0.00 (95% confidence interval (CI) −0.08 to 0.07)%]. Annualized rates of confirmed (≤3.9 mmol/l) or severe hypoglycaemia were lower with Gla-300 than with Gla-100 during the night (31% difference in rate ratio over 6 months) and at any time (24 h, 14% difference). Consistent reductions were observed in percentage of participants with ≥1 hypoglycaemic event. Severe hypoglycaemia at any time (24 h) was rare (Gla-300: 2.3%; Gla-100: 2.6%). Weight gain was low (<1 kg) in both groups, with less gain with Gla-300 [LS mean difference −0.28 kg (95% CI −0.55 to −0.01); p = 0.039]. Both treatments were well tolerated, with similar rates of adverse events.ConclusionGla-300 provides comparable glycaemic control to Gla-100 in a large population with a broad clinical spectrum of T2DM, with consistently less hypoglycaemia at any time of day and less nocturnal hypoglycaemia.

Glycaemic control and hypoglycaemia benefits with insulin glargine 300 U/mL extend to people with type 2 diabetes and mild‐to‐moderate renal impairment

“…While the mean insulin doses increased in both treatment arms, there was a tendency for a larger increase with Gla‐300, consistent with findings reported for the overall EDITION population 14, 15, 16. Although speculative, one possible reason underlying this greater increase in dose with Gla‐300 than Gla‐100 may be related to the lower bioavailability of Gla‐300, owing to the greater stability of its subcutaneous depot that might make it more prone to enzymatic inactivation compared with Gla‐100 18. It is also important to consider that the dose changes observed may be a consequence of the treat‐to‐target design of the EDITION trials; dose increases were to be expected given that participants switched to, or initiated, a new basal insulin in this study because they were uncontrolled on their previous treatment.…”

Инсулин Тожео — Новый Базальный Инсулин Длительного Действия. Часть 2. Клиническая Эффективность И Безопасность

“…Данные трех клинических исследований EDITION (1, 2 и 3) с участием лиц, страдающих СД-2, также опу-бликованы в составе patient-level-метаанализа [102][103][104]. Следует подчеркнуть, что метаанализ на основе индивидуальных данных пациентов превосходит мета-анализ интегральных данных в случае потенциального модифицирующего влияния характеристик пациента на терапевтический эффект исследуемого воздействия [70,121].…”

“…Следует подчеркнуть, что в объединенном анализе СД-2-исследований (EDITION-1, 2 и 3, 6-месячные данные) [102][103][104] риск ночных подтвержденных и тя-желых гипогликемий уменьшался на 31 % у участни-ков, леченных Gla-300 с большей на 12 % дозой инсу-лина и меньшим увеличением веса.…”

“…Причина такого различия в дозах инсулина в настоящее время умозрительна. Метаболит М1 является главной активной молекулой, циркулирующей после инъекции как Gla-300, так и Gla-100 [118], однако более вероятно, что большее вре-мя нахождения в подкожном пространстве Gla-300 vs Gla-100 [14] может вести к увеличению ферментатив-ной активности тканевых пептидаз в месте инъекции [104]. Это наблюдение формирует мысль о несколько более низкой биодоступности Gla-300 по сравнению с Gla-100.…”

Achieve control: a pragmatic clinical trial of insulin glargine 300 U/mL versus other basal insulins in insulin-naïve patients with type 2 diabetes

“…In the randomized, controlled Phase III EDITION clinical trial program, Gla-300 was shown to be non-inferior to Gla-100 in reducing HbA1c levels, without increasing the risk of hypoglycemia versus Gla-100 in patients with type 1 diabetes (T1D) or T2D at 6 months [11][12][13][14] and at 1 year [15,16]. The proportion of patients who experienced ≥1 confirmed (blood glucose [BG] ≤70 mg/dL) or severe nocturnal hypoglycemic event was significantly lower for Gla-300 than for Gla-100 [17]. Data from the EDITION clinical trial program also supports the use of Gla-300 in different patient populations, its ease of use in insulinnaïve patients, and less hypoglycemia when switching from twice-daily insulin [11][12][13]15,16].…”