Initiating Insulin Therapy in Type 2 Diabetes

Abstract

OBJECTIVE—Safety and efficacy of biphasic insulin aspart 70/30 (BIAsp 70/30, prebreakfast and presupper) were compared with once-daily insulin glargine in type 2 diabetic subjects inadequately controlled on oral antidiabetic drugs (OADs). RESEARCH DESIGN AND METHODS—This 28-week parallel-group study randomized 233 insulin-naive patients with HbA1c values ≥8.0% on >1,000 mg/day metformin alone or in combination with other OADs. Metformin was adjusted up to 2,550 mg/day before insulin therapy was initiated with 5–6 units BIAsp 70/30 twice daily or 10–12 units glargine at bedtime and titrated to target blood glucose (80–110 mg/dl) by algorithm-directed titration. RESULTS—A total of 209 subjects completed the study. At study end, the mean HbA1c value was lower in the BIAsp 70/30 group than in the glargine group (6.91 ± 1.17 vs. 7.41 ± 1.24%, P < 0.01). The HbA1c reduction was greater in the BIAsp 70/30 group than in the glargine group (−2.79 ± 0.11 vs. −2.36 ± 0.11%, respectively; P < 0.01), especially for subjects with baseline HbA1c >8.5% (−3.13 ± 1.63 vs. −2.60 ± 1.50%, respectively; P < 0.05). More BIAsp 70/30–treated subjects reached target HbA1c values than glargine-treated subjects (HbA1c ≤6.5%: 42 vs. 28%, P < 0.05; HbA1c <7.0%: 66 vs. 40%, P < 0.001). Minor hypoglycemia (episodes/year) was greater in the BIAsp 70/30 group than in the glargine group (3.4 ± 6.6 and 0.7 ± 2.0, respectively; P < 0.05). Weight gain and daily insulin dose at study end were greater for BIAsp 70/30–treated subjects than for glargine-treated subjects (weight gain: 5.4 ± 4.8 vs. 3.5 ± 4.5 kg, P < 0.01; insulin dose: 78.5 ± 39.5 and 51.3 ± 26.7 units/day, respectively). CONCLUSIONS—In subjects with type 2 diabetes poorly controlled on OADs, initiating insulin therapy with twice-daily BIAsp 70/30 was more effective in achieving HbA1c targets than once-daily glargine, especially in subjects with HbA1c >8.5%.

Subject‐driven titration of biphasic insulin aspart 30 twice daily is non‐inferior to investigator‐driven titration in Chinese patients with type 2 diabetes inadequately controlled with premixed human insulin: A randomized, open‐label, parallel‐group, multicenter trial

“…This insulin dose was in line with the Initiation of Insulin to Reach A1c Target study (INITIATE Study) and Yang's trial25, 26. The two groups ended with similar doses, suggesting that patients successfully managed the dose titration themselves after training, and adjusted insulin dose as required to achieve good control of blood glucose.…”

Comment on: Nauck MA, Duran S, Kim D et al (2007) A comparison of twice-daily exenatide and biphasic insulin aspart in patients with type 2 diabetes who were suboptimally controlled with sulfonylurea and metformin: a non-inferiority study. Diabetologia 50:259–267

“…In this study, insulin dose adjustment was simply left to the investigator. It is not clear from the paper what intensity of follow-up, selfmonitoring, or dose adjustment to what target occurred, but at 52 weeks the premix insulin dose was only 24 U/day, well below doses used in recent studies [4][5][6][7][8], and below doses normally encountered in clinical practice. This appeared not to be the result of hypoglycaemia in this particular group of patients-the reported hypoglycaemia rate was as low with insulin as with the glucagon-like peptide-1 mimetic.…”

“…The result of this is that the blood glucose control achieved was relatively poor in the insulin-treated group (a fall of 0.9% in HbA 1c from a baseline of 8.6%) when compared with nearly all recently published treat-to-target studies with insulin therapy in people with type 2 diabetes [4][5][6][7][8]. In these, final HbA 1c is typically <7.0% (achieved by 68% of participants in the INITIATE study [5], and eventually by 77% of participants in the 1-2-3 study, where a third premix injection was an option) [6].…”

“…In these, final HbA 1c is typically <7.0% (achieved by 68% of participants in the INITIATE study [5], and eventually by 77% of participants in the 1-2-3 study, where a third premix injection was an option) [6]. The LanMet study achieved an HbA 1c of 7.1%, but this was from baseline levels of 9.1% [8].…”

Comparison of the pharmacokinetics and pharmacodynamics of biphasic insulin aspart and insulin glargine in people with type 2 diabetes

“…Addition of either form of basal insulin produced a HbA 1c concentration of 7% in most patients, but there was significantly less hypoglycaemia in the patients receiving insulin glargine than in those receiving NPH. Raskin et al [6] randomised patients failing on oral hypoglycaemic agents to receive either insulin glargine at bedtime or premixed (70% protaminated insulin aspart/30 soluble insulin aspart) insulin twice a day for 24 weeks. Oral hypoglycaemic agents were stopped with the exception of metformin (optimised to 1,550-2,550 mg) and glitazones.…”