Long-Acting Insulin Analogs Versus Insulin Pump Therapy for the Treatment of Type 1 and Type 2 Diabetes

Abstract

Insulin pump therapy (continuous subcutaneous insulin infusion [CSII]) is now an established form of intensive insulin treatment. It is pertinent to ask, however, if multiple daily injection (MDI) regimens based on new long-acting insulin analogs such as glargine and detemir have now replaced the need for CSII. In type 1 diabetes, CSII reduces the frequency of severe hypoglycemia compared with isophane-based MDIs, but the rate of severe hypoglycemia is usually similar on glargine-or detemir-based MDIs compared with isophane-based MDIs. CSII reduces A1C and glycemic variability compared with isophane-based MDIs; but glargine and detemir do not improve A1C or variability in many patients, particularly those who are prone to hypoglycemia. Head-to-head comparisons of CSII with MDI based on glargine indicate lower A1C, fructosamine, or glucose levels on CSII. It can be concluded that long-acting insulin analogs have not yet replaced the need for insulin pump therapy in type 1 diabetes, and CSII is the best current therapeutic option for some type 1 diabetic subjects. In type 2 diabetes, CSII and MDI produce similar glycemic control, although there is little study of MDI based on long-acting analogs compared with pumps. It is possible that CSII will be beneficial in selected patient groups with type 2 diabetes, but this requires further study. Diabetes Care 31 (Suppl. 2):S140-S145, 2008F or many decades, it has been accepted that poor glycemic control in insulin injection-treated diabetes is mainly due to the inadequacies of insulin pharmacology (1,2). Regular (shortacting) insulin is absorbed too slowly from the subcutaneous site to control postprandial hyperglycemia, and the delayed absorption then results in late hypoglycemia. Both of these problems have now been much improved by the introduction of more quickly absorbed monomeric insulins (3). The problems of longacting insulin formulations such as isophane and lente have taken longer to improve: they produce "hill-like" blood concentration and action profiles, resulting in a peak of over-insulinization in the middle of the night with a consequent risk of hypoglycemia, and a waning in insulinization before breakfast, resulting in fasting hyperglycemia (1,2,4). Moreover, these delayed-action insulin suspensions also have huge variability of subcutaneous absorption (1), contributing to much of the unpredictability in within-and between-day blood glucose control.The development of insulin pump therapy (continuous subcutaneous insulin infusion [CSII]) nearly 30 years ago (5) did much to overcome the problems of long-acting insulin injections. The constancy of the basal delivery allows for a near-flat blood insulin profile, adjustable at preset times to suit the changing needs of the patient throughout the day. The controlled delivery of small insulin amounts substantially reduces glycemic variability (6,7). For many years, these advantages have allowed a superiority of insulin pump therapy over insulin injection regimens, at least as far as the frequency of hypoglycem...

Continuous subcutaneous insulin infusion versus multiple daily insulin injections in type 1 diabetes: a meta-analysis

“…Notably, the reduction of HbA1c with CSII was not associated with an increased risk of severe hypoglycemia. This result is consistent with those of a previous meta-analysis on a patient-level data from three small trials [19], and of two larger meta-analyses which included trials applying CSII with RHI [1,2].…”

“…However, glycemic targets are not reached with this approach in all patients. Continuous subcutaneous insulin infusion (CSII) with external pumps is a treatment option for patients with type 1 diabetes unsatisfactorily controlled with multiple daily injection regimens [1,2].…”

Availability of insulin pump therapy in clinical practice

“…Patients with Type 1 diabetes are currently treated with either multiple daily insulin injections or insulin pumps, also referred to as continuous subcutaneous insulin infusion [3,4]. Meta-analyses have shown insulin pump use to be associated with HbA 1c approximately 3 mmol ⁄ mol (0.3%) lower than multiple daily insulin injections, and data in clinical practice have shown an improvement of 4 mmol ⁄ mol (0.4%) after switching from multiple daily insulin injections to an insulin pump [5][6][7].…”

Continuous subcutaneous insulin infusion vs. multiple daily injections

“…Finally, in the last decade, research is focused on comparison of CSII (with rapid-acting insulin analogues as the gold standard) and MDI with meal boluses of rapid-acting insulin analogues and basal insulinisation with long-acting insulin analogues. Data on the safety and efficacy of this two therapeutic regimens show that they are equal [10,11] or are mildly in favor of CSII, especially in certain groups of patients [14,15]. Some head-to-head comparisons of CSII with MDI based on glargine indicate lower HbA1C or glucose levels on CSII.…”