Abstract
AIM: To determine the safety of a higher starting dose of basal insulin in overweight/obese patients with type 2 diabetes (T2D). MATERIALS AND METHODS: This 16-week, randomized, multicentre, open-label trial enrolled adults with T2D (body mass index 25-40 kg/m(2) ) and suboptimal glycaemic control (glycated haemoglobin [HbA1c] 7.5-11.0% [58-97 mmol/mol] and fasting plasma glucose [FPG] >9.0 mmol/L) with two to three oral anti-hyperglycaemic drugs at 51 centres in China. Patients were randomized (1:1) to a higher (0.3 U/kg) or standard (0.2 U/kg) starting dose of insulin glargine 100 U/mL, which was then titrated to achieve a self-monitored fasting blood glucose (FBG) of 4.4 to 5.6 mmol/L. The primary endpoint was the percentage of patients with ≥1 episode of overall confirmed hypoglycaemia (≤3.9 mmol/L or severe). RESULTS: At the end of study (n = 866), 11.0% patients treated with the 0.3 U/kg starting insulin dose experienced overall confirmed hypoglycaemia versus 8.6% of patients treated with 0.2 U/kg (estimated difference 2.1%, 95% confidence interval - 1.68, 5.89). The proportions of patients with symptomatic (9.8% vs 7.0%; P = 0.128) and nocturnal hypoglycaemia (2.7% vs 1.2%; P = 0.102) were similar in the two groups. There were no events of severe hypoglycaemia or FBG <3.0 mmol/L during the 16-week treatment, and achievement of HbA1c <7.0% (53 mmol/mol) (37.1% vs 37.1%) or FPG <5.6 mmol/L (15.9% vs 16.3%), <6.1 mmol/L (27.6% vs 26.1%), or < 7.0 mmol/L (48.8% vs 48.3%) without hypoglycaemia were comparable in the two groups. Moreover, the mean time was shorter (4.53, 3.95 and 2.74 weeks vs 5.51, 5.21 and 3.64 weeks) and number of titrations was lower (3.5, 3.0 and 2.0 vs 4.3, 4.0 and 2.8) to achieve self-monitored FBG targets of <5.6, <6.1 and <7.0 mmol/L in the higher versus the standard insulin dose group (all P < 0.01). CONCLUSIONS: Among overweight/obese patients with T2D, a higher insulin starting dose was as safe as the standard starting dose, and self-monitored FBG targets were achieved earlier with the higher versus the standard dose.