An overview of insulin therapy for the non-specialist

Abstract

Nearly all health professionals, whatever their practice or speciality, now have contact with a significant number of insulin-using people with diabetes. People with type 1 diabetes are nearly universally managed on more complex insulin regimens, increasingly with complex support technology, and with some understanding of the concepts underlying these needed by anyone with responsibility for other aspects of their health care. People with type 2 diabetes usually come to insulin therapy in time, now with a prevalence for insulin administration of ≈50%, thanks to improved management of associated health risks giving longer life expectancy. But while some understandings have simplified the usual approach (basal insulin, self-adjustment dose algorithms), the advent of other medical products offering cardio-renal protection, the use of insulin in combination with these, and the marketing of novel insulin analogues and biosimilars, have all added complexity to clinical decision making. However for the insulin user in the mainstream of care (ambulatory diabetes services in primary and secondary care) the broad principles of choice and management of insulin therapy are fairly easily applied. In the current article, the complexity is dissected and addressed, some of the stigma around insulin therapy is neutralised, and the fundamental approach in regular care drawn into focus.

Plain Language Summary

Insulin therapy is used in their diabetes lifetime by nearly all people with type 2 diabetes (T2DM), as well as in all people with type 1 diabetes (T1DM). In T2DM this is in the context of the usual progression of islet B-cell secretory failure, but also very often in the context of other conditions, from cancer or steroid therapy to acute arterial events or major surgery. Its prescription in these circumstances means that, in pharmaco-epidemiological studies, insulin use is invariably associated with poor health outcomes, but in a series of major RCTs of 5–15 years duration no excess of vascular or oncological adverse health outcomes was found. Physiologically insulin secretion occurs in two scenarios, namely basal insulin at night and between meals (≈50%), and in short (≈4 h) bursts with meals (≈50%). The former suppresses liver glucose production, which in its absence causes plasma glucose to rise threefold to around 12 mmol/l (but much higher if metabolic stress or with sugar-containing drinks). Meal-time insulin secretion in addition promotes glucose storage in skeletal muscle. People with T1DM, having no endogenous insulin secretion, thus require a multiple injection regimen (basal + meal-time), or pumped insulin, often now moderated by continuous glucose monitoring (CGM). Basal and meal-time preparations of pharmaceutical insulin analogues are also used for T2DM, with GLP-1RA and metformin usually continued. The starting regimen is normally basal only, usually with insulin glargine (100 U/ml), originator or biosimilar, while insulin degludec or glargine 300 U/ml can have advantage as basal insulins where true 24-h cover is found to be needed. Weekly insulins (developmental or marketed) may have a role in injection acceptability in T2DM, at a cost of some increase in hypoglycaemia. In ambulatory care a meal-time insulin analogue, originator or biosimilar, is added when required, often after some years on basal insulin. Meal insulins are also used in insulin pumps. Hypoglycaemia is a significant issue in T1DM, limiting insulin dosing, but can be helped by CGM, with or without pumps, and careful dose adjustment. It is a much lesser issue in T2DM, until meal-time insulins are introduced, or in people of thinner phenotype, whence again expertise in dose adjustment may be needed. Body weight gain with insulin is usually modest, particularly if basal insulin is begun appropriately before glycosuria has influenced calorie balance. In mainstream ambulatory care the broad principles of insulin therapy are fairly easily applied, the main resources being team familiarity with a basal insulin (glargine/biosimilar), a finger-prick glucose-monitoring system, basic patient education on use of these, and time to supervise dose titration. Beginning with a fixed dose (e.g. 10 U/day) and increasing by 2 U twice a week is simple, but may take months of persistent input to reach target fasting plasma glucose levels. In conclusion, insulin is a usual therapy in both T1DM and T2DM, and in the latter initially at least is fairly easily applied, in combination with other glucose-lowering agents. However it can be more challenging in the context of the technology used in T1DM, once meal-time insulin is added to basal in T2DM, and when dose requirements are complex and unstable in conjunction with other medical conditions.