Continuous subcutaneous insulin infusion in diabetes: patient populations, safety, efficacy, and pharmacoeconomics

Abstract

The level of glycaemic control necessary to achieve optimal short-term and long-term outcomes in subjects with type 1 diabetes mellitus (T1DM) typically requires intensified insulin therapy using multiple daily injections or continuous subcutaneous insulin infusion. For continuous subcutaneous insulin infusion, the insulins of choice are the rapid-acting insulin analogues, insulin aspart, insulin lispro and insulin glulisine. The advantages of continuous subcutaneous insulin infusion over multiple daily injections in adult and paediatric populations with T1DM include superior glycaemic control, lower insulin requirements and better health-related quality of life/patient satisfaction. An association between continuous subcutaneous insulin infusion and reduced hypoglycaemic risk is more consistent in children/adolescents than in adults. The use of continuous subcutaneous insulin infusion is widely recommended in both adult and paediatric T1DM populations but is limited in pregnant patients and those with type 2 diabetes mellitus. All available rapid-acting insulin analogues are approved for use in adult, paediatric and pregnant populations. However, minimum patient age varies (insulin lispro: no minimum; insulin aspart: ≥2 years; insulin glulisine: ≥6 years) and experience in pregnancy ranges from extensive (insulin aspart, insulin lispro) to limited (insulin glulisine). Although more expensive than multiple daily injections, continuous subcutaneous insulin infusion is cost-effective in selected patient groups. This comprehensive review focuses on the European situation and summarises evidence for the efficacy and safety of continuous subcutaneous insulin infusion, particularly when used with rapid-acting insulin analogues, in adult, paediatric and pregnant populations. The review also discusses relevant European guidelines; reviews issues that surround use of this technology; summarises the effects of continuous subcutaneous insulin infusion on patients' health-related quality of life; reviews relevant pharmacoeconomic data; and discusses recent advances in pump technology, including the development of closed-loop 'artificial pancreas' systems. © 2015 The Authors. Diabetes/Metabolism Research and Reviews Published by John Wiley & Sons Ltd.

Keywords: continuous subcutaneous insulin infusion; diabetes mellitus; paediatric; pharmacoeconomics; pregnancy; rapid-acting insulin analogue.

Figure 1

Continuous subcutaneous insulin infusion therapy penetration rates in patients with type 1 diabetes mellitus in European countries 14

Figure 2

Meta‐analysis: effects of CSII and MDI on HbA_1c in adult and paediatric patients with T1DM 7. A meta‐analysis of 12 randomised controlled trials involving a comparison of CSII and MDI in adult patients with T1DM demonstrated a statistically significant difference in HbA_1c in favour of CSII of 0.29% (95% CI, 0.06% to 0.52%). In paediatric patients, meta‐analysis of eight trials also favoured CSII (0.22% [0.03% to 0.41%]). CI, confidence interval; CSII, continuous subcutaneous insulin infusion; MDI, multiple daily injections; NPH, neutral protamine Hagedorn; T1DM, type 1 diabetes mellitus

Figure 3

Treatment satisfaction in children treated with CSII (insulin aspart) or MDI (neutral protamine Hagedorn and insulin aspart) over a 2‐year period 112. Treatment satisfaction was measured using the Diabetes Treatment Satisfaction Questionnaire (DTSQ) in children with T1DM treated with CSII (n = 34; dotted lines, diamonds) or MDI (n = 38; straight lines, squares). The results are presented as mean ± 95% CI. CI, confidence interval; CSII, continuous subcutaneous insulin infusion; MDI, multiple daily injections; T1DM, type 1 diabetes mellitus * p < 0.05

Figure 4

Components of a closed‐loop insulin delivery system 119. Interstitial glucose levels, measured by the sensor, are transmitted to the controller, which contains a control algorithm. This modulates the pump's insulin infusion rate in real time. All communication is wireless

Figure 5

Nocturnal glycaemic control in adolescent patients with type 1 diabetes mellitus using an ‘artificial pancreas’ or a sensor‐augmented pump 74. Sensor glucose profiles obtained with an artificial pancreas (A) and a sensor‐augmented insulin pump (B). The type(s) of insulin used in this study was not specified. Solid black line and adjacent dashed lines: median glucose level and interquartile range. Circles and vertical lines: median capillary glucose measurements and interquartile range. The horizontal dashed lines indicate blood glucose levels of 180 mg/dL (10.0 mmol/L) and 63 mg/dL (3.5 mmol/L [the threshold for hypoglycaemia])