Glycaemic control and hypoglycaemia with new insulin glargine 300 U/ml versus insulin glargine 100 U/ml in people with type 2 diabetes using basal insulin and oral antihyperglycaemic drugs: the EDITION 2 randomized 12-month trial including 6-month extension
H Yki-Järvinen, R M Bergenstal, G B Bolli, M Ziemen, M Wardecki, I Muehlen-Bartmer, M Maroccia, M C Riddle, H Yki-Järvinen, R M Bergenstal, G B Bolli, M Ziemen, M Wardecki, I Muehlen-Bartmer, M Maroccia, M C Riddle
Abstract
Aims: To compare the efficacy and safety of new insulin glargine 300 U/ml (Gla-300) with insulin glargine 100 U/ml (Gla-100) over 12 months of treatment in people with type 2 diabetes using basal insulin and oral antihyperglycaemic drugs (OADs).
Methods: EDITION 2 (NCT01499095) was a randomized, 6-month, multicentre, open-label, two-arm, phase IIIa study investigating once-daily Gla-300 versus Gla-100, plus OADs (excluding sulphonylureas), with a 6-month safety extension.
Results: Similar numbers of participants in each group completed 12 months of treatment [Gla-300, 315 participants (78%); Gla-100, 314 participants (77%)]. The reduction in glycated haemoglobin was maintained for 12 months with both treatments: least squares (LS) mean (standard error) change from baseline -0.55 (0.06)% for Gla-300 and -0.50 (0.06)% for Gla-100; LS mean difference -0.06 [95% confidence interval (CI) -0.22 to 0.10)%]. A significant relative reduction of 37% in the annualized rate of nocturnal confirmed [≤3.9 mmol/l (≤70 mg/dl)] or severe hypoglycaemia was observed with Gla-300 compared with Gla-100: rate ratio 0.63 [(95% CI 0.42-0.96); p = 0.031], and fewer participants experienced ≥1 event [relative risk 0.84 (95% CI 0.71-0.99)]. Severe hypoglycaemia was infrequent. Weight gain was significantly lower with Gla-300 than Gla-100 [LS mean difference -0.7 (95% CI -1.3 to -0.2) kg; p = 0.009]. Both treatments were well tolerated with a similar pattern of adverse events (incidence of 69 and 60% in the Gla-300 and Gla-100 groups).
Conclusions: In people with type 2 diabetes treated with Gla-300 or Gla-100, and non-sulphonylurea OADs, glycaemic control was sustained over 12 months, with less nocturnal hypoglycaemia in the Gla-300 group.
Keywords: basal insulin; insulin glargine; oral antihyperglycaemic drugs; type 2 diabetes.
© 2015 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.
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References
- Becker RH, Dahmen R, Bergmann K, Lehmann A, Jax T, Heise T. New insulin glargine 300 ‐1 provides a more even activity profile and prolonged glycemic control at steady state compared with insulin glargine 100 ‐1 . Diabetes Care 2015; 38: 637–643.
- Kunt T, Snoek FJ. Barriers to insulin initiation and intensification and how to overcome them. Int J Clin Pract 2009; 63 (Suppl. 164): 6–10.
- Yki‐Järvinen H, Bergenstal R, Ziemen M et al. New insulin glargine 300 U/mL versus glargine 100 U/mL in people with type 2 diabetes using oral agents and basal insulin: glucose control and hypoglycaemia in a 6‐month randomised controlled trial (EDITION 2). Diabetes Care 2014; 37: 3235–3243.
- Bolli G, Riddle M, Bergenstal R et al. New insulin glargine 300 U/mL versus glargine 100 U/mL in insulin naïve people with type 2 diabetes using anithyperglycemic drugs: glucose control and hypoglycemia in a randomized controlled trial (EDITION 3). Diabetes Obes Metab 2015; 17: 386–394.
- Riddle MC, Bolli GB, Ziemen M, Muehlen‐Bartmer I, Bizet F, Home PD. New insulin glargine 300 units/mL versus glargine 100 units/mL in people with type 2 diabetes using basal and mealtime insulin: glucose control and hypoglycemia in a 6‐month randomized controlled trial (EDITION 1). Diabetes Care 2014; 37: 2755–2762.
- Levey AS, Coresh J, Balk E et al. National Kidney Foundation practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Ann Intern Med 2003; 139: 137–147.
- American Diabetes Association . Defining and reporting hypoglycemia in diabetes: a report from the American Diabetes Association Workgroup on Hypoglycemia. Diabetes Care 2005; 28: 1245–1249.
- Bradley C, Lewis KS. Measures of psychological well‐being and treatment satisfaction developed from the responses of people with tablet‐treated diabetes. Diabet Med 1990; 7: 445–451.
- Lewis KS, Bradley C, Knight G, Boulton AJ, Ward JD. A measure of treatment satisfaction designed specifically for people with insulin‐dependent diabetes. Diabet Med 1988; 5: 235–242.
- Garber AJ, King AB, Del Prato S et al. Insulin degludec, an ultra‐longacting basal insulin, versus insulin glargine in basal‐bolus treatment with mealtime insulin aspart in type 2 diabetes (BEGIN Basal‐Bolus Type 2): a phase 3, randomised, open‐label, treat‐to‐target non‐inferiority trial. Lancet 2012; 379: 1498–1507.
- Zinman B, Philis‐Tsimikas A, Cariou B et al. Insulin degludec versus insulin glargine in insulin‐naive patients with type 2 diabetes: a 1‐year, randomized, treat‐to‐target trial (BEGIN Once Long). Diabetes Care 2012; 35: 2464–2471.
- Gough SC, Bhargava A, Jain R, Mersebach H, Rasmussen S, Bergenstal RM. Low‐volume insulin degludec 200 units/ml once daily improves glycemic control similarly to insulin glargine with a low risk of hypoglycemia in insulin‐naive patients with type 2 diabetes: a 26‐week, randomized, controlled, multinational, treat‐to‐target trial: the BEGIN LOW VOLUME trial. Diabetes Care 2013; 36: 2536–2542.
- Riddle MC, Yki‐Järvinen H, Bolli GB et al. One‐year sustained glycaemic control and less hypoglycaemia with new insulin glargine 300 U/ml compared with 100 U/ml in people with type 2 diabetes using basal plus meal‐time insulin: the EDITION 1 12‐month randomized trial, including 6‐month extension. Diabetes Obes Metab 2015; 17: 835–842.
- Ritzel R, Roussel R, Bolli GB et al. Patient‐level meta‐analysis of EDITION 1, 2 and 3: glycaemic control and hypoglycaemia with new insulin glargine 300 U/mL versus glargine 100 U/mL in people with type 2 diabetes. Diabetes Obes Metab 2015; 17: 859–867.
- Matsuhisa M, Koyama M, Cheng XN, Shimizu S, Hirose T, on behalf of the EDITION JP 1 study group . New insulin glargine 300 U/mL: glycemic control and hypoglycemia in Japanese people with T1DM (EDITION JP 1). Diabetes 2014; 63(Suppl. 1A): LB22.
- Home P, Bergenstal R, Riddle MC et al. Glycemic control and hypoglycemia with new insulin glargine 300 U/mL in people with T1DM (EDITION 4). Diabetes 2014; 63(Suppl. 1A): LB19.
- Terauchi Y, Koyama M, Cheng XN, Shimizu S, Hirose T. Glycemic control and hypoglycemia in Japanese people with T2DM receiving new insulin glargin 300 U/mL in combination with OADs (EDITION JP 2). Diabetes 2014; 63: LB24.
Source: PubMed