Rapid-Acting Insulin Analogues Versus Regular Human Insulin: A Meta-Analysis of Effects on Glycemic Control in Patients with Diabetes

Introduction: The aim of this meta-analysis was to investigate the impact of rapid-acting insulin analogues (RAIAs) and regular human insulin (RHI) on glycemic control, including long- and short-term glycemic variability as measured by glycated haemoglobin (HbA1c) and pre- and postprandial glucose (PPG).

Methods: PubMed was searched for studies published between 1999 and 29 June 2016. Randomised controlled trials of patients with diabetes that assessed the effects of RAIAs or RHI on glycemic control, focusing on preprandial glucose, PPG and HbA1c, were included. Only studies that reported both means and standard deviations for those outcomes were analysed; from these data, weighted mean differences and 95% confidence intervals were generated to yield overall point estimates. The primary outcomes of the meta-analysis were the mean differences between RAIAs and RHI at the end of the study in PPG, preprandial glucose, and HbA1c.

Results: Twenty-seven studies (n = 7452) were included. The difference in PPG between RAIA- and RHI-treated patients was significant-in favour of RAIAs-in patients with type 1 diabetes (T1D) [- 22.2 mg/dL; 95% confidence interval (CI) - 27.4, - 17.0 mg/dL; P < 0.0001] but not in those with type 2 diabetes (T2D). For preprandial glucose, there was a non-significant trend favouring RHIs in T1D; no data were available for patients with T2D. In patients with T1D, the between-group difference in end-of-treatment (EOT) HbA1c favoured RAIAs (- 0.13%; 95% CI - 0.18, - 0.08%; P < 0.0001), but was not significant in patients with T2D. The main study limitations were the small number and heterogeneity of the included studies.

Conclusions: These results demonstrate that RAIAs are more effective at reducing PPG and improving HbA1c than RHIs in T1D. More data are required to assess the effect of these agents on glucose control in T2D. In patients with diabetes, the risk of complications is increased by poor control of blood glucose levels and high blood glucose variability. Complications may include cardiovascular disease, eye problems and amputation. Control and variability of blood glucose levels can be evaluated using a range of measures, including (i) glycated haemoglobin (HbA1c) level at the end of the treatment period; (ii) change in HbA1c level during the treatment period; (iii) fasting plasma glucose level; (iv) postprandial glucose (PPG) level; (v) change in blood glucose level after a meal. PPG levels following a meal are an important measure of overall metabolic control in diabetes, and reduction of glycemic variability (GV) can be achieved via reductions in PPG. Both rapid-acting insulin analogues (RAIAs; aspart, glulisine and lispro) and regular human insulin (RHI) are widely used in the management of diabetes. Using data from 27 randomised controlled trials involving more than 7000 patients, we investigated the impact of RAIAs and RHI on measures of glycemic control and variability in patients with type 1 diabetes (T1D) or type 2 diabetes (T2D). Our results show that, in patients with T1D, RAIAs are more effective than RHI at reducing PPG excursions and HbA1c. This indicates that glycemic control is better with RAIAs than with RHI. More data are required to assess the effects of RAIAs and RHI on glycemic control and variability in patients with T2D.

Plain language summary: In patients with diabetes, the risk of complications is increased by poor control of blood glucose levels and high blood glucose variability. Complications may include cardiovascular disease, eye problems and amputation. Control and variability of blood glucose levels can be evaluated using a range of measures, including (i) glycated haemoglobin (HbA1c) level at the end of the treatment period; (ii) change in HbA1c level during the treatment period; (iii) fasting plasma glucose level; (iv) postprandial glucose (PPG) level; (v) change in blood glucose level after a meal. PPG levels following a meal are an important measure of overall metabolic control in diabetes, and reduction of glycemic variability (GV) can be achieved via reductions in PPG. Both rapid-acting insulin analogues (RAIAs; aspart, glulisine and lispro) and regular human insulin (RHI) are widely used in the management of diabetes. Using data from 27 randomised controlled trials involving more than 7000 patients, we investigated the impact of RAIAs and RHI on measures of glycemic control and variability in patients with type 1 diabetes (T1D) or type 2 diabetes (T2D). Our results show that, in patients with T1D, RAIAs are more effective than RHI at reducing PPG excursions and HbA1c. This indicates that glycemic control is better with RAIAs than with RHI. More data are required to assess the effects of RAIAs and RHI on glycemic control and variability in patients with T2D.