Intranasal insulin therapy: the clinical realities

Abstract

Summary To evaluate metabolic control and safety parameters (hypoglycaemia frequency and nasal mucosa physiology), 31 insulin-dependent diabetic patients were treated with intranasal insulin at mealtimes for i month and with subcutaneous fast-acting insulin at meals for another month in an open, crossover randomized trial. During both treatment periods the patients were treated with intermediate-acting insulin at bedtime. Six of the patients were withdrawn from the study during intranasal insulin therapy due to metabolic dysregulation. Serum insulin concentrations increased more rapidly and decreased more quickly during intranasal as compared with subcutaneous insulin administration. Metabolic control deteriorated, as assessed by haemoglobin Aic concentrations, slightly but significantly after intranasal as compared with subcutaneous insulin therapy. The bioavailability of intranasally applied insulin was low, since intranasal insulin doses were approximately 20 times higher than subcutaneous doses. The frequency of hypoglycaemia was similar during intranasal and subcutaneous insulin therapy, and nasal mucosa physiology was unaffected after intranasal insulin. We conclude that due to low bioavailability and to a high rate of therapeutic failure, intranasal insulin treatment is not a realistic alternative to subcutaneous insulin injections at the present time. [Diabetologia (1995) The limitations of intensive insulin therapy are mainly due to the pharmacokinetic properties of subcutaneously injected insulin, resulting in an increased frequency of hypoglycaemia [2]. Whereas avoiding hypoglycaemia with intensive insulin therapy only seems possible by raising blood glucose levels, a more physiological insulin administration might potentially reduce blood glucose without increasing the frequency of hypoglycaemia [3]. In this context, intranasal insulin administration has gained considerable interest, since after intranasal application of insulin, plasma insulin concentrations increase more rapidly and return to basal levels more quickly than after subcutaneous insulin injections [4]. Furthermore, this "needle-free" way of administering insulin avoids the problems inherent in insulin injections.Clinical data on intranasal insulin therapy are relatively scarce, since previous investigations were either pharmacokinetic studies, carried out in healthy

Alternative routes of insulin delivery

“…Clinical studies in patients with Type 1 and Type 2 diabetes have revealed a rapid but relatively short‐lived increase in plasma insulin following nasal administration with multiple doses required to control postprandial hyperglycaemia [66,67]. However, metabolic control was frequently inferior to s.c. insulin and many patients suffered local nasal irritation [67–69]. More recently, a lyophilized nasal insulin preparation containing sodium glycocholate given preprandially achieved glycaemic control equivalent to a regimen of twice daily NPH insulin in patients with Type 2 diabetes over a 4‐month period [70].…”

Intranasally administered insulin intended for prevention of type 1 diabetes—a safety study in healthy adults

“…Owing to the high molecular weight of the insulin peptide and the lack of lipophilicity, insulin poorly crosses the cell membranes, if administered to the mucosal membranes without absorption adjuvants. These characteristics also make nasal insulin a poor candidate for the treatment of patients with type 1 diabetes 6–8. Meaningful metabolic effects are recognised after intranasal insulin administration only if absorption enhancers are used, and even then large doses are required 9.…”

TechnosphereTM/Insulin - proof of concept study with a new insulin formulation for pulmonary delivery

“…Since the early days of insulin therapy, alternative routes of insulin administration have been investigated in attempts to overcome these limitations (Olsen et al, 1994). As an example, nasal delivery of insulin has been extensively studied, but the bioeffectiveness, is poor, and the nasal mucosa may be irritated by repeated intranasal insulin administration (Hilsted et al, 1995).…”