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 A(1c) 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 A(1c) 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 A(1c) 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 A(1c). 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.
RCT Entities:
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 insulinglargine is non-inferior to three-times daily prandial insulinlispro 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 insulinglargine taken once daily at the same time every day or to insulinlispro administered three times per day. The primary objective was to compare the change in haemoglobin A(1c) 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 insulinglargine and 210 to insulinlispro. Mean haemoglobin A(1c) decrease in the insulinglargine group was -1.7% (from 8.7% [SD 1.0] to 7.0% [0.7]) and -1.9% in the insulinlispro 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 A(1c) 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 insulinlispro group, whereas insulinlispro better controlled postprandial blood glucose throughout the day (p<0.0001). The incidence of hypoglycaemic events was less with insulinglargine 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 insulinglargine than for insulinlispro (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 A(1c). We conclude that insulinglargine 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 insulinlispro. FUNDING: Sanofi-Aventis.
Authors: Matthew Riddle; Richard Pencek; Supoat Charenkavanich; Karen Lutz; Ken Wilhelm; Lisa Porter Journal: Diabetes Care Date: 2009-06-05 Impact factor: 19.112