28-week, randomized, multicenter, open-label, parallel-group phase III trial to investigate the efficacy and safety of biphasic insulin aspart 70 thrice-daily injections vs twice-daily injections of biphasic insulin aspart 30 in patients with type 2 diabetes

Takashi Kadowaki, Tomoyuki Nishida, Kohei Kaku, Takashi Kadowaki, Tomoyuki Nishida, Kohei Kaku

Abstract

Aims/Introduction: An insulin analogue formulation with a 7:3 ratio of rapid-acting and intermediate-acting fractions, biphasic insulin aspart 70 (BIAsp70) was developed to supplement basal insulin between meals and mimic the physiological pattern of postprandial insulin secretion.

Materials and methods: We carried out a randomized, open-label study to compare the efficacy and safety profiles of BIAsp70 and an insulin analogue formulation with a 3:7 ratio of rapid-acting and intermediate-acting fractions (BIAsp30) in type 2 diabetes mellitus patients. Patients were randomized and received either thrice-daily BIAsp70 (n = 145) or twice-daily BIAsp30 (n = 144) for 28 weeks. The primary end-point was glycated hemoglobin (HbA1c) after 16 weeks of treatment.

Results: Non-inferiority of BIAsp70 vs BIAsp30 was confirmed and superiority was established with a between-group difference (BIAsp70-BIAsp30) in HbA1c after 16 weeks of treatment of -0.35% (95% CI: -0.51 to -0.19; P < 0.0001 for superiority). The mean postprandial glucose increment (19.96 vs 54.35 mg/dL; P < 0.0001) and M-value (12.99 vs 17.94; P < 0.0001) at 16 weeks were smaller in the BIAsp70 group than in the BIAsp30 group, and were maintained at 28 weeks. Pre-breakfast glucose (157.9 vs 140.7 mg/dL), total insulin dose (46.8 vs 38.1 U/day) and weight gain (+1.94 vs 1.23 kg) at week 28 were greater in the BIAsp70 group. Incidence of nocturnal hypoglycemia was significantly lower with BIAsp70 vs BIAsp30 (1.23 vs 3.21 events/subject year; P = 0.0002) at week 28.

Conclusions: Thrice-daily BIAsp70 was superior to twice-daily BIAsp30 in terms of HbA1c change, with less variation in daytime plasma glucose profiles. BIAsp70 was well tolerated, with a lower incidence of nocturnal hypoglycemia vs BIAsp30. This trial was registered with ClinicalTrial.gov (no. NCT00318786). (J Diabetes Invest, doi: 10.1111/j.2040-1124.2010.00015.x, 2010).

Keywords: Biphasic insulin aspart 70; Postprandial hyperglycemia; Type 2 diabetes mellitus.

Figures

Figure 1
Figure 1
Disposition of subjects in the trial.
Figure 2
Figure 2
Mean profiles of HbA1c in the two groups throughout the study.
Figure 3
Figure 3
Plasma glucose profiles in the two groups at 16 weeks.

References

    1. Diabetes Control and Complications Trial Research Group . The effect of intensive treatment of diabetes on the development and progression of long‐term complications in insulin‐dependent diabetes mellitus. N Engl J Med 1993; 329: 977–986
    1. UK Prospective Diabetes Study Group . Intensive blood‐glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet 1998; 352: 837–853
    1. Ohkubo Y, Kishikawa H, Araki E, et al. Intensive insulin therapy prevents the progression of diabetic microvascular complications in Japanese patients with non‐insulin‐dependent diabetes mellitus: a randomized prospective 6‐year study. Diabetes Res Clin Pract 1995; 28: 103–117
    1. DECODE Study Group . Glucose tolerance and mortality: comparison of WHO and American Diabetes Association diagnostic criteria. Lancet 1999; 354: 617–621
    1. Tominaga M, Eguchi H, Manaka H, et al. Impaired glucose tolerance is a risk factor for cardiovascular disease, but not impaired fasting glucose. The Funagata Diabetes Study. Diabetes Care 1999; 22: 920–924
    1. Monnier L, Colette C, Owens DR. Integrating glycaemic variability in the glycaemic disorders of type 2 diabetes: a move towards a unified glucose tetrad concept. Diabetes Metab Res Rev 2009; 25: 393–402
    1. Peter R, Okoseime OE, Rees A, Owens DR. Postprandial glucose – a potential therapeutic target to reduce cardiovascular mortality. Curr Vasc Pharmacol 2009; 7: 68–74
    1. Zaccard F, Pitocco D, Ghirlanda G. Glycemic risk factors of diabetic vascular complications: the role of glycemic variability. Diabetes Metab Res Rev 2009; 25: 199–207
    1. Kawamori R, Kaku K, Kasuga M, et al. Safety and effectiveness of biphasic insulin aspart 30 (BIAsp 30) in patients with type 2 diabetes (T2D)—IMPROVE Study in Japan (in Japanese). Jpn Pharmacol Ther 2009; 37: 233–241
    1. Hirao K, Arai K, Yamauchi M, et al. Six‐month multicentric, open‐label, randomized trial of twice‐daily injections of biphasic insulin aspart 30 versus multiple daily injections of insulin aspart in Japanese type 2 diabetic patients (JDDM 11). Diabetes Res Clin Pract 2008; 79: 171–176
    1. Masuda H, Sakamoto M, Irie J, et al. Comparison of twice‐daily injections of biphasic insulin lispro and basal‐bolus therapy: glycaemic control and quality‐of‐life of insulin‐naïve type 2 diabetic patients. Diabetes Obes Metab 2008; 10: 1261–1265
    1. Japan Diabetes Society . Practice of insulin therapy (in Japanese) In: Japan Diabetes Society (ed). Treatment Guide for Diabetes. Bunkodo, Tokyo, 2008: 55–59
    1. Iwamoto Y, Akanuma Y, Niimi H, et al. Comparison between insulin aspart and rapid‐acting human insulin in type 1 diabetes (IDDM) patients treated with basal‐bolus insulin therapy. Phase III clinical trial in Japan (in Japanese). J Jpn Diabetes Soc 2001; 44: 799–811
    1. Schlichtkrull J, Munck O, Jersild M. The M‐value, an index of blood‐sugar control in diabetics. Acta Med Scand 1965; 177: 95–102
    1. Japan Diabetes Society . Indices for glycemic control (in Japanese) In: Japan Diabetes Society (ed). Treatment Guide for Diabetes. Bunkodo, Tokyo, 2008: 25.
    1. Diabetes Control and Complications Trial Research Group . Early worsening of diabetic retinopathy in the Diabetes Control and Complications Trial. Arch Ophthalmol 1998; 116: 874–886
    1. Kikuchi M, Irie S, Eto T, et al. Thrice‐daily BIAsp70 more closely mimics physiological insulin secretion compared with twice‐daily BIAsp30. European Association for the Study of Diabetes 44th Annual Meeting Abstract Volume 2008; S402: 994.

Source: PubMed

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