Comparison of insulin degludec with insulin glargine in insulin-naive subjects with Type 2 diabetes: a 2-year randomized, treat-to-target trial

• Published in: Diabetic medicine Vol. 30; no. 11; pp. 1298 - 1304
• Main Authors: Rodbard, H. W., Cariou, B., Zinman, B., Handelsman, Y., Philis-Tsimikas, A., Skjøth, T. V., Rana, A., Mathieu, C.
• Format: Journal Article Web Resource
• Language: English
• Published: Oxford Blackwell Publishing Ltd 01.11.2013; Blackwell; Wiley Subscription Services, Inc; Blackwell Science; BlackWell Publishing Ltd
• Subjects: Administration, Oral; Analysis of Variance; Biological and medical sciences; Blood Glucose - metabolism; Diabetes; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - drug therapy; Diabetes. Impaired glucose tolerance; Drug Administration Schedule; Endocrine pancreas. Apud cells (diseases); Endocrinologie, métabolisme & nutrition; Endocrinology, metabolism & nutrition; Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Feeding. Feeding behavior; Fundamental and applied biological sciences. Psychology; Glycated Hemoglobin A - metabolism; Human health sciences; Humans; Hypoglycemia - chemically induced; Hypoglycemic Agents - administration & dosage; Hypoglycemic Agents - adverse effects; Insulin Glargine; Insulin, Long-Acting - administration & dosage; Insulin, Long-Acting - adverse effects; Medical sciences; Sciences de la santé humaine; Treatment Outcome; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Vertebrates: endocrinology; Endocrinopathy; Type 2 diabetes; Human; Obesity; Nutrition; Nutrition disorder; Metabolic diseases; Target; Hypoglycemic agent; Randomization; Insulin glargine; Treatment; Clinical trial; Endocrinology; Nutritional status; Comparative study
• ISSN: 0742-3071; 1464-5491; 1464-5491
• DOI: 10.1111/dme.12303

Aims The aim of this study was to compare long‐term safety and efficacy of the basal insulin analogue degludec with glargine in insulin‐naive subjects with Type 2 diabetes. Methods This open‐label trial included a 52‐week core period followed by a 52‐week extension. Participants were randomized 3:1 to once‐daily degludec or glargine, administered with metformin ± dipeptidyl peptidase‐4 inhibitors. Basal insulin was titrated to target pre‐breakfast plasma glucose 3.9–4.9 mmol/l. Results At end of treatment (104 weeks), mean HbA1c reductions were similar for degludec and glargine; estimated treatment difference between degludec and glargine was 1 mmol/mol (95% CI −1 to 3) [0.07% (95% CI −0.07 to 0.22)], P = 0.339 in the extension trial set (degludec 551, glargine 174), comprising subjects who completed core trial and continued into the extension trial. Overall confirmed hypoglycaemia rates (1.72 vs. 2.05 episodes/patient‐year), rates of adverse events possibly or probably related to trial product (0.19 events/patient‐year), weight gain (2.7 vs. 2.4 kg) and mean daily insulin doses (0.63 U/kg) were similar between treatments in the safety analysis set (degludec 766, glargine 257) comprising all treated subjects. Rates of nocturnal confirmed hypoglycaemia (0.27 vs. 0.46 episodes/patient‐year; P = 0.002) and severe hypoglycaemia (0.006 vs. 0.021 episodes/patient‐year, P = 0.023) were significantly lower with degludec for the safety analysis set (analysis based on intention‐to‐treat full analysis set comprising all randomized subjects). Conclusions In Type 2 diabetes, insulin degludec in combination with oral anti‐diabetic drugs, safely and effectively improves long‐term glycaemic control, with a significantly lower risk of nocturnal hypoglycaemia as compared with glargine. What's new? Insulin degludec, a basal insulin analogue, uses a novel protraction mechanism, resulting in a flat, stable profile and a duration of action greater than 42 h. Consistent with its pharmacokinetic and pharmacodynamic profile, insulin degludec in combination with oral anti‐diabetic drugs provided long‐term glycaemic control similar to insulin glargine with a lower risk for nocturnal hypoglycaemia in insulin‐naive patients with Type 2 diabetes, in a 1‐year, randomized study. This extension study reports 2‐year data, confirming that insulin degludec in combination with oral anti‐diabetic drugs maintains stable glycaemic control with a sustained benefit in reducing hypoglycaemic risk in Type 2 diabetes.