Once-daily basal insulin glargine versus thrice-daily prandial insulin lispro in people with type 2 diabetes on oral hypoglycaemic agents (APOLLO) : an open randomised controlled trial

Background: As type 2 diabetes mellitus progresses, oral hypoglycaemic agents often fail to maintain blood glucose control and insulin is needed. We investigated whether the addition of once-daily insulin glargine is non-inferior to three-times daily prandial insulin lispro in overall glycaemic control in adults with inadequately controlled type 2 diabetes mellitus taking oral hypoglycaemic agents. Methods: In the 44-week, parallel, open study that was undertaken in 69 study sites across Europe and Australia, 418 patients with type 2 diabetes mellitus that was inadequately controlled by oral hypoglycaemic agents were randomly assigned to either insulin glargine taken once daily at the same time every day or to insulin lispro administered three times per day. The primary objective was to compare the change in haemoglobin A1c from baseline to endpoint (week 44) between the two regimens. Randomisation was done with a central randomisation service. Analysis was per protocol. This study is registered with ClinicalTrials.gov, number NCT00311818. Findings: 205 patients were randomly assigned to insulin glargine and 210 to insulin lispro. Mean haemoglobin A1c decrease in the insulin glargine group was -1·7% (from 8·7% [SD 1·0] to 7·0% [0·7]) and -1·9% in the insulin lispro group (from 8·7% [1·0] to 6·8% [0·9]), which was within the predefined limit of 0·4% for non-inferiority (difference=0·157; 95% Cl -0·008 to 0·322). 106 (57%) patients reached haemoglobin A1c of 7% or less in the glargine group and 131 (69%) in the lispro group. In the glargine group, the fall in mean fasting blood glucose (-4·3 [SD 2·3] mmol/L vs -1·8 [2·3] mmol/L; p<0·0001) and nocturnal blood glucose (-3·3 [2·8] mmol/L vs -2·6 [2·9] mmol/L; p=0·0041) was better than it was in the insulin lispro group, whereas insulin lispro better controlled postprandial blood glucose throughout the day (p<0·0001). The incidence of hypoglycaemic events was less with insulin glargine than with lispro (5·2 [95% CI 1·9-8·9] vs 24·0 [21-28] events per patient per year; p<0·0001). Respective mean weight gains were 3·01 (SD 4·33) kg and 3·54 (4·48) kg. The improvement of treatment satisfaction was greater for insulin glargine than for insulin lispro (mean difference 3·13; 95% CI 2·04-4·22). Interpretation: A therapeutic regimen involving the addition of either basal or prandial insulin analogue is equally effective in lowering haemoglobin A1c. We conclude that insulin glargine provides a simple and effective option that is more satisfactory to patients than is lispro for early initiation of insulin therapy, since it was associated with a lower risk of hypoglycaemia, fewer injections, less blood glucose self monitoring, and greater patient satisfaction than was insulin lispro. Funding: Sanofi-Aventis

Intravenous NPA for the treatment of infarcting myocardium early: InTIME-II, a double-blind comparison on of single-bolus lanoteplase vs accelerated alteplase for the treatment of patients with acute myocardial infarction

Aims to compare the efficacy and safety of lanoteplase, a single-bolus thrombolytic drug derived from alteplase tissue plasminogen activator, with the established accelerated alteplase regimen in patients presenting within 6 h of onset of ST elevation acute myocardial infarction. Methods and Results 15 078 patients were recruited from 855 hospitals worldwide and randomized in a 2:1 ratio to receive either lanoteplase 120 KU. kg-1 as a single intravenous bolus, or up to 100 mg accelerated alteplase given over 90 min. The primary end-point was all-cause mortality at 30 days and the hypothesis was that the two treatments would be equivalent. By 30 days, 6.61% of alteplase-treated patients and 6.75% lanoteplase-treated patients had died (relative risk 1.02). Total stroke occurred in 1.53% alteplase- and 1.87% lanoteplase-treated patients (ns); haemorrhagic stroke rates were 0.64% alteplase and 1.12% lanoteplase (P=0.004). The net clinical deficit of 30-day death or non-fatal disabling stroke was 7.0% and 7.2%, respectively. By 6 months, 8.8% of alteplase-treated patients and 8.7% of lanoteplase-treated patients had died. Conclusion Single-bolus weight-adjusted lanoteplase is an effective thrombolytic agent, equivalent to alteplase in terms of its impact on survival and with a comparable risk-benefit profile. The single-bolus regimen should shorten symptoms to treatment times and be especially convenient for emergency department or out-of-hospital administration. (C) 2000 The European Society of Cardiology