The Treat-to-Target Trial

Abstract

OBJECTIVE -To compare the abilities and associated hypoglycemia risks of insulin glargine and human NPH insulin added to oral therapy of type 2 diabetes to achieve 7% HbA 1c .RESEARCH DESIGN AND METHODS -In a randomized, open-label, parallel, 24-week multicenter trial, 756 overweight men and women with inadequate glycemic control (HbA 1c Ͼ7.5%) on one or two oral agents continued prestudy oral agents and received bedtime glargine or NPH once daily, titrated using a simple algorithm seeking a target fasting plasma glucose (FPG) Յ100 mg/dl (5.5 mmol/l). Outcome measures were FPG, HbA 1c , hypoglycemia, and percentage of patients reaching HbA 1c Յ7% without documented nocturnal hypoglycemia.RESULTS -Mean FPG at end point was similar with glargine and NPH (117 vs. 120 mg/dl [6.5 vs. 6.7 mmol/l]), as was HbA 1c (6.96 vs. 6.97%). A majority of patients (ϳ60%) attained HbA 1c Յ7% with each insulin type. However, nearly 25% more patients attained this without documented nocturnal hypoglycemia (Յ72 mg/dl [4.0 mmol/l]) with glargine (33.2 vs. 26.7%, P Ͻ 0.05). Moreover, rates of other categories of symptomatic hypoglycemia were 21-48% lower with glargine.CONCLUSIONS -Systematically titrating bedtime basal insulin added to oral therapy can safely achieve 7% HbA 1c in a majority of overweight patients with type 2 diabetes with HbA 1c between 7.5 and 10.0% on oral agents alone. In doing this, glargine causes significantly less nocturnal hypoglycemia than NPH, thus reducing a leading barrier to initiating insulin. This simple regimen may facilitate earlier and effective insulin use in routine medical practice, improving achievement of recommended standards of diabetes care.

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

“…A similar problem bedevilled a previously published exenatide comparison with insulin, in which a change of −1.1% from a baseline HbA 1c level of 8.3% was achieved with insulin glargine [3]; in the original treat-to-target study, Riddle and colleagues achieved a 45% greater reduction in HbA 1c , from 8.6% at baseline to 7.0% [4]. Similar or better results were achieved with insulin detemir [7].…”

“…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].…”

Efficacy and safety of switching from basal insulin to once‐daily insulin degludec/insulin aspart in Japanese patients with inadequately controlled type 2 diabetes: A 4‐week, randomized, open‐label, treat‐to‐target study

“…The present prospective, 4‐week, single‐center, randomized, open‐label, parallel‐group, treat‐to‐target study14 was carried out to compare the efficacy and safety of IDegAsp or basal insulin in combination with OHA therapy.…”

Glycemic control and adherence to basal insulin therapy in Taiwanese patients with type 2 diabetes mellitus

“…The clinical trials showed that the use of basal insulin as an add‐on to OAD in patients with type 2 diabetes achieved 7% HbA1c, and approximately half of the patients experienced symptomatic hypoglycemia20, 21, 22, 23, 24. However, in real‐world practice, a retrospective USA study and two prospective studies in Ireland and Japan found that approximately just 20% of the patients taking basal insulin could achieve HbA1c <7% with a low rate of hypoglycemia16, 25, 26.…”