OBJECTIVETo determine whether glargine is noninferior to detemir regarding the percentage of patients reaching A1C <7% without symptomatic hypoglycemia ≤3.1 mmol/l.RESEARCH DESIGN AND METHODSIn this 24-week trial, 973 insulin-naive type 2 diabetic patients on stable oral glucose-lowering drugs with A1C 7.0–10.5% were randomized to glargine once daily or detemir twice daily. Insulin doses were systematically titrated.RESULTS27.5 and 25.6% of patients reached the primary outcome with glargine and detemir, respectively, demonstrating the noninferiority of glargine. Improvements in A1C were −1.46 ± 1.09% for glargine and −1.54 ± 1.11% for detemir (P = 0.149), with similar proportions of patients achieving A1C <7% (P = 0.254) but more detemir-treated patients reaching A1C <6.5% (P = 0.017). Hypoglycemia risk was similar. Weight gain was higher for glargine (difference: 0.77 kg, P < 0.001). Glargine doses were lower than detemir doses: 43.5 ± 29.0 vs. 76.5 ± 50.5 units/day (P < 0.001).CONCLUSIONSIn insulin-naive type 2 diabetic patients, glargine reached similar control as detemir, with more weight gain, but required significantly lower doses.

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Our analyses suggest that there is no clinically relevant difference in efficacy or safety between insulin detemir and insulin glargine for targeting hyperglycaemia. However, to achieve the same glycaemic control insulin detemir was often injected twice-daily in a higher dose but with less weight gain, while insulin glargine was injected once-daily, with somewhat fewer injection site reactions.

There is no conclusive evidence for a large increase in the risk of mood disorders associated with migration.

Glucose clamp studies assessing the time-action profile of long-acting insulin analogues have reported conflicting results. In an attempt to reconcile the data, we organised an expert meeting of four leading European clamp groups, during which consensus was reached on some but not all points discussed. In this paper, which reflects our personal views only, we aim to provide guidance for readers and reviewers on the interpretation of this type of clamp study and to clarify its inherent limitations.Glucose clamp studies are either performed manually or using an automated procedure, but differences in clamp methodology hardly seem a satisfactory explanation for the conflicting results. (Un)conscious investigator-related bias, especially during manual studies, cannot be ruled out, despite attempts at blinding the study insulin during the clamp.The duration of action of study insulins is influenced by many factors, such as glucose and insulin levels prior to injection, endogenous insulin secretion, insulin dose, definitions used for onset and end of action, and insulin sensitivity (which is influenced by the necessity of fasting during the clamp). These factors limit the translation of clamp study results into daily practice.Because of the inherent limitations of the glucose clamp technique and the lack of reproducibility of the outcomes, its results should be regarded as no more than an indication of the clinical action profile of long-acting insulin preparations.

Aims/hypothesis The aim of this analysis was to quantify the relationship between the frequency of hypoglycaemia and various glucose cut-off points for the definition of hypoglycaemia, within a range of HbA 1c strata. Methods Data from two trials examining insulin glargine dose titration in 12,837 type 2 diabetic participants starting insulin therapy were combined. Curves for hypoglycaemia frequency plotted against endpoint HbA 1c level were constructed, using a range of glucose cut-off points for hypoglycaemia. Results During the 12-week study period, 3,912 patients recorded 21,592 hypoglycaemic episodes, comprising 242 severe, 8,871 symptomatic and 12,479 asymptomatic events, corresponding to hypoglycaemia event rates of 0.10, 3.8 and 5.3 events per patient year. Increasing the hypoglycaemia cutoff point from, for instance, <3.1 to <3.9 mmol/l more than doubled the percentage of affected patients, e.g. from 17.7 to 43.3% at HbA 1c 7.0-7.2%. At higher hypoglycaemia cut-off points the proportion of patients having only asymptomatic hypoglycaemia increased, e.g. from 30.7% at <3.1 mmol/l to 61.7% of patients at a cut-off point of <3.9 mmol/l. In sensitivity analysis, 121 of 1,756 patients with at least one self-monitored blood glucose value <3.1 mmol/l experienced severe hypoglycaemia, compared with 149 of 3,912 patients with a self-monitored blood glucose level of <3.9 mmol/l. Thus, to identify 28 more patients with severe hypoglycaemia, the number of patients experiencing only non-severe hypoglycaemia more than doubled. Conclusions/interpretation The glucose cut-off point defining hypoglycaemia greatly affects the reported frequency of hypoglycaemia. When hypoglycaemia is to be defined by a predetermined glucose level, to have clinical relevance the cut-off should be set at a lower level than the threshold of 3.9 mmol/l proposed by the American Diabetes Association.

We compared the combined use of basal insulin, metformin and insulin secretagogues with a combination of basal insulin and metformin in patients with type 2 diabetes starting basal insulin analogue therapy. This analysis was part of a 24-week trial, in which 964 insulin-naive patients with type 2 diabetes inadequately controlled on oral agents (including metformin) were randomized to insulin glargine or detemir. Secretagogues were stopped or maintained at the site-investigators' discretion. During the study, 57.6% of patients continued their secretagogue treatment. Compared with patients stopping secretagogues, those who continued experienced significantly more hypoglycaemia and weight gain. Insulin doses, however, were significantly lower: 0.6 ± 0.4 versus 0.8 ± 0.4 U/kg/day (p < 0.001). The difference between groups in mean HbA1c reduction was not statistically significant. In conclusion, in type 2 diabetic patients starting basal insulin analogue therapy, continuing both metformin and secretagogues results in more hypoglycaemia and weight gain and lower insulin doses than only maintaining metformin.

The L2T3 study will extend the evidence on both the efficacy and the effects on quality of life and treatment satisfaction of the long-acting insulin analogs glargine and detemir. Additionally, it will increase our understanding of the factors important to the (self-)management of type 2 diabetes patients starting insulin.