EPG Diabetes Knowledge Centre
Low risk of hypoglycaemia
NovoNorm® is associated with a low risk of hypoglycaemia in type 2 diabetes
There are compelling reasons to suggest that insulin secretagogues, targeted to prandial glucose excursions, provide the most physiological strategy for treating type 2 diabetes. However, the most widely used secretagogues, the sulphonylureas, are slow in their onset of action and result in continuous stimulation of beta cells across dosing intervals, regardless of plasma glucose concentration.27Thus, insulin output is not synchronised to need, so hypoglycaemia is an inevitable risk. This risk can be reduced if the patient takes care to consume meals at regular intervals and supplements carbohydrate intake with additional snacks, but compliance to such regimens may be poor.
A review of severe hypoglycaelic events in long term, one-year, comparative studies involving sulphonylureas shows that treatment with NovoNorm® achieved a relative risk reduction of severe hypoglycaemia of 60% compared to commonly used sulphonylureas. This difference in risk was manifest despite identical levels of metabolic control with all treatments.28
Data from comparative trials show the incidence of major hypoglycaemia in patients with type 2 diabetes receiving NovoNorm® to be 60% lower than in those receiving sulphonylureas.28
Missed or irregular meals have been identified as the most common precipitating event for sulphonylurea-associated hospital admissions for severe hypoglycaemia.29,30 With NovoNorm®, delaying or missing a meal merely means delaying or missing a dose. As the duration of action of NovoNorm® is not unnecessarily prolonged, this situation does not carry the same threat of hypoglycaemia as is the case during sulphonylurea therapy.
The ability of NovoNorm® to minimise the risk of hypoglycaemia in everyday life, where it is not always possible to stick to rigid meal schedules, was clearly demonstrated in a study of 43 patients with well-controlled type 2 diabetes who received either mealtime NovoNorm® or glibenclamide given according to label recommendations.31 These patients were subsequently assessed with and without omission of their midday meal (and hence their midday dose of NovoNorm®). In this study, there were significant differences between treatment when the influence of omitting the midday meal was considered (p = 0.014). The mean minimum blood glucose level remained unchanged at 4.3 mmol/l in NovoNorm®-treated patients, whereas omission of lunch in glibenclamide-treated patients led to a fall from 4.3 to 3.4 mmol/l. Six episodes of hypoglycaemia (four requiring treatment) occurred, all in glibenclamide treated patients and all in association with omission of lunch.
Omission of lunch in patients with type 2 diabetes receiving prandial NovoNorm®was not associated with any occurrences of severe, post-lunchtime hypoglycaemia. In contrast, 24% of patients treated with glibenclamide experienced a severe hypoglycaemic event when they missed lunch.31
A similar finding was made in a 16-week, placebo-controlled study involving 408 patients naïve to pharmacotherapy who were allowed to follow flexible meal patterns.20 Despite significant improvements in metabolic control in the NovoNorm®-treated group, with 84% of patients achieving an HbA1C of less than 7.5%, NovoNorm® was associated with episodes of severe hypoglycaemia in three patients only (0.9%).
Finally, a very low incidence of hypoglycaemia associated with the flexible use of NovoNorm® in every day clinical practice was reported in a prospective investigation in a clinical setting, involving nearly 6000 patients.17 Over a mean treatment period of 46 days, only 49 hypoglycaemic events had occurred in this cohort. Of these, 38 were classified as mild and only five as severe, but no adverse sequelae were reported.