Intermediate acting versus long acting insulin for type 1 diabetes mellitus

Diabetes mellitus type 1 is a chronic disease with short and long term complications. The treatment for this disease is insulin administration, with basal and bolus insulin preparations being its main stay. Neutral Protamine Hagedorn (NPH) insulin had previously been considered the standard of care for basal insulin replacement in blood glucose lowering for people with type 1 diabetes mellitus. Over the years, newer and longer acting insulins with a more physiological action profile became available: insulin ultralente, and later insulin glargine and insulin detemir. Their theoretical advantages lead to the thought of a beneficial effect on glucose level and rate of complications, such as very low levels of glucose or long term complications. The aim of this review was to assess whether this theoretical advantage is translated into real-life benefits, by comparing the effect of long acting insulins to intermediate acting insulins on diabetes control.
Twenty-three studies fulfilled our inclusion criteria with a total of 3872 and 2915 participants in the intervention and in the control group, respectively. The methodological quality of all the studies was rated intermediate to low. Trials duration was no longer than one year. The level of glycosylated haemoglobin, a marker of diabetes control, was lower in the long acting insulin group, but the observed difference was of doubtful clinical significance. Longer acting insulins were superior mostly in their nocturnal effect, which resulted in a lower level of fasting glucose levels and fewer episodes of nocturnal hypoglycaemia. No data on long term complications were available.
The currently available data can not substantiate conclusions on the benefits and risks of long acting insulins, and long-term data are of need.

Authors' conclusions: 

Long acting insulin preparations seem to exert a beneficial effect on nocturnal glucose levels. Their effect on the overall diabetes control is clinically unremarkable. Their use as a basal insulin regimen for type 1 diabetes mellitus warrants further substantiation.

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Background: 

Diabetes mellitus type 1 is a chronic disease with short and long term complications. Its goals of therapy are to eliminate the symptoms of hyperglycaemia, reduce the long term microvascular and macrovascular complications and allow the patients to achieve a normal life-style. Basal insulin replacement for insulin dependent patients can be achieved with either intermediate or long acting insulin preparations.

Objectives: 

To assess the effects of intermediate acting versus long acting insulin preparations for basal insulin replacement in type 1 diabetic patients.

Search strategy: 

We searched MEDLINE, EMBASE and The Cochrane Library, as well as reference lists, databases of ongoing trials, and requests from authors of included trials.

Selection criteria: 

Randomised controlled trials, assessing long acting insulin preparations compared to intermediate acting insulin preparations, in type 1 diabetic patients.

Data collection and analysis: 

Two reviewers independently scanned the titles. Data were extracted and analysed accordingly.

Main results: 

Twenty-three randomised controlled trials were identified. A total of 3872 and 2915 participants in the intervention and in the control group, respectively, were analysed. The weighted mean difference (WMD) for the level of glycosylated haemoglobin was -0.08 (95% confidence interval (CI) -0.12 to -0.04) in favour of the long acting insulin arm. The WMD between the groups in fasting plasma and blood glucose levels was -0.63 (95% CI -0.86 to -0.40) and -0.86 (95% CI -1.00 to -0.72) in favour of the long acting insulins. The odds ratio for a patient on long acting insulin to develop any type of hypoglycaemia was 0.93 (95% CI 0.8 to 1.08) compared to that of a patient on intermediate acting insulins. The OR for severe hypoglycaemic episodes was 0.73 (95% CI 0.61 to 0.87), and 0.70 (95% CI of 0.63 to 0.79) for nocturnal episodes. The WMD between the long and intermediate insulin groups for hypoglycaemic events per 100 patient follow up days was -0.77 (95% CI -0.89 to -0.65), -0.0 (95% CI -0.02 to 0.02) and -0.40 (95% CI -0.45 to -0.34) for overall, severe, and nocturnal hypoglycaemic episodes. Weight gain was more prominent in the control group. No difference was noted in the quantity or quality of severe adverse events or deaths.

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