Intensive replacement of basal insulin on patients with type 1 diabetes given rapid-acting insulin analog at mealtime - A 3-month comparsion between administration of NPH insulin four times daily and glargine insulin at dinner or bedtime

Department of Internal Medicine, Università degli Studi di Perugia, Perugia, Umbria, Italy
Diabetes Care (Impact Factor: 8.57). 05/2003; 26(5):1490-6. DOI: 10.2337/diacare.26.5.1490
Source: PubMed

ABSTRACT To establish differences in blood glucose between different regimens of optimized basal insulin substitution in type 1 diabetic patients given lispro insulin at meals, i.e., NPH injected four times a day versus glargine insulin once daily at dinner or at bedtime.
A total of 51 patients with type 1 diabetes on intensive therapy (NPH four times/day and lispro insulin at each meal) were randomized to three different regimens of basal insulin substitution while continuing lispro insulin at meals: continuation of NPH four times/day (n = 17), once daily glargine at dinnertime (n = 17), and once daily glargine at bedtime (n = 17) for 3 months. Blood glucose targets were fasting, preprandial, and bedtime concentrations at 6.4-7.2 mmol/l and 2 h after meals at 8.0-9.2 mmol/l. The primary end point was HbA(1c).
Mean daily blood glucose was lower with dinnertime glargine (7.5 +/- 0.2 mmol/l) or bedtime glargine (7.4 +/- 0.2 mmol/l) versus NPH (8.3 +/- 0.2 mmol/l) (P < 0.05). A greater percentage of blood glucose values were at the target value with glargine at dinner and bedtime versus those with NPH (P < 0.05). HbA(1c) at 3 months did not change with NPH but decreased with glargine at dinnertime (from 6.8 +/- 0.2 to 6.4 +/- 0.1%) and glargine at bedtime (from 7.0 +/- 0.2 to 6.6 +/- 0.1%) (P < 0.04 vs. NPH). Total daily insulin doses were similar with the three treatments, but with glargine there was an increase in basal and a decrease in mealtime insulin requirements (P < 0.05). Frequency of mild hypoglycemia (self-assisted episodes, blood glucose < or =4.0 mmol/l) was lower with glargine (dinnertime 8.1 +/- 0.8 mmol/l, bedtime 7.7 +/- 0.9 mmol/l) than with NPH (12.2 +/- 1.3 mmol/l) (episodes/patient-month, P < 0.04). In-hospital profiles confirmed outpatient blood glucose data and indicated more steady plasma insulin concentrations at night and before meals with glargine versus NPH (P < 0.05). There were no differences between glargine given at dinnertime and at bedtime.
Regimens of basal insulin with either NPH four times/day or glargine once/day in type 1 diabetic patients both result in good glycemic control. However, the simpler glargine regimen decreases the HbA(1c) level and frequency of hypoglycemia versus NPH. In contrast to NPH, which should be given at bedtime, insulin glargine can be administered at dinnertime without deteriorating blood glucose control.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Long-acting insulin analogues have been developed to mimic the physiology of basal insulin secretion more closely than human insulin formulations (Neutral Protamine Hagedorn, NPH). However, the clinical evidence in favour of analogues is still controversial. Although their major benefit as compared with NPH is a reduction in the hypoglycaemia risk, some cost/effectiveness analyses have not been favourable to analogues, largely due to their higher price. Nevertheless, these new formulations have conquered the insulin market. Human insulin represents currently no more than 20% of market share. Despite (in fact because of) the widespread use of insulin analogues it remains critical to analyse the pharmacodynamics (PD) of basal insulin formulations appropriately to interpret the results of clinical trials correctly. Importantly, these data may help physicians in tailoring insulin therapy to patients' individual needs and, additionally, when clinical evidence is not available, to optimise insulin treatment. For patients at low risk for/from hypoglycaemia, it might be acceptable and also cost-effective not to use long-acting insulin analogues as basal insulin replacement. Conversely, in patients with a higher degree of insulin deficiency and increased risk for hypoglycaemia, analogues are the best option due to their more physiological profile, as has been shown in PD and clinical studies. From this perspective optimising basal insulin treatment, especially in Type 2 diabetes patients who are less prone to hypoglycaemia, would be suitable making significant resources available for other relevant aspects of diabetes care.
    Diabetes Obesity and Metabolism 01/2014; DOI:10.1111/dom.12256 · 5.18 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: BACKGROUND: The prescribing habits of insulin in Bulgaria at national level were analyzed during 1991-1994 and published in 1997 but the authorization of lots of new medicines and introduction of health insurance fund (NHIF) in 2000 changed treatment patterns. OBJECTIVE: To analyze the prescribing habits of insulin and to compare them with the previous study as well as with the contemporary diabetes therapy. METHODS: The sample of 29,281 prescriptions for 2,440 patients was collected in 2004 and systematized according to the share of the prescribed insulin by international nonproprietary name (INN), duration of action, trade names, manufacturer, dosage forms and number of prescribed defined daily doses (DDD). The pharmacotherapy cost was calculated on the basis of the average monthly cost of ambulatory prescription. RESULTS: There is an increase with approximately 39,400 insulin users for 10 years period. During 2004 the consumption in DDD/per patient/per day was 1.46 DDD. The percentage of prescribed different action modes of insulin presented in DDD was 51% premixes (mix of short acting and long acting insulin), 17% short acting human insulin, 25% long acting human insulin, 7% human insulin analogues (genetic modified insulin). In comparison with the study published ten years ago the changes in the prescribing patterns are in the complete replacement of the animal insulin with the human ones, introduction of the human analogues and changes in the internal structure of prescribing patterns pointing at switch mainly towards the intensified therapeutic regime. The changes in the prescribing practice and introduction of the new insulin and therapeutic schemes lead to the increase in the cost of ambulatory drug therapy paid by the NHIF at 23,345,280 Euro in 2004. CONCLUSIONS: The changes in the insulin prescribing could be evaluated as significant improvement in the therapeutic practice and close to the contemporary requirements but there is still delay in the introduction of the intensified therapy for all patients. The usage of insulin analogues also lag behind in comparison with the economically developed countries.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: To examine the safety, effectiveness, and cost effectiveness of long acting insulin for type 1 diabetes.
    BMJ British medical journal 10/2014; 349. DOI:10.1136/bmj.g5459 · 16.30 Impact Factor