'Human' insulin versus animal insulin in people with diabetes mellitus.

BACKGROUND

Human insulin was introduced for the routine treatment of diabetes mellitus in the early 1980s without adequate comparison of efficacy to animal insulin preparations. First reports of altered hypoglycaemia awareness after transfer to human insulin made physicians and especially patients uncertain about potential adverse effects of human insulin.

OBJECTIVES

To assess the effects of different insulin species by evaluating their efficacy (in particular glycaemic control) and adverse effects profile (mainly hypoglycaemia).

SEARCH STRATEGY

A highly sensitive search for randomised controlled trials combined with key terms for identifying studies on human versus animal insulin was performed using The Cochrane Library, MEDLINE and EMBASE. We also searched reference lists and databases of ongoing trials. Date of latest search: July 2004.

SELECTION CRITERIA

We included randomised controlled clinical trials with diabetic patients of all ages that compared human to animal (for the most part purified porcine) insulin. Trial duration had to be at least one month in order to achieve reliable results on the main outcome parameter glycated haemoglobin.

DATA COLLECTION AND ANALYSIS

Trial selection as well as evaluation of study quality was performed by two independent reviewers. The quality of reporting of each trial was assessed according to a modification of the quality criteria as specified by Schulz and by Jadad.

MAIN RESULTS

Altogether 2156 participants took part in the 45 randomised controlled studies that were discovered through extensive search efforts. Though many studies had a randomised, double-blind design, most studies were of poor methodological quality. Purified porcine and semi-synthetic insulin were most often investigated. No significant differences in metabolic control or hypoglycaemic episodes between various insulin species could be elucidated. Insulin dose and insulin antibodies did not show relevant dissimilarities.

AUTHORS' CONCLUSIONS: A comparison of the effects of human and animal insulin as well as of the adverse reaction profile did not show clinically relevant differences. Many patient-oriented outcomes like health-related quality of life or diabetes complications and mortality were never investigated in high-quality randomised clinical trials. The story of the introduction of human insulin might be repeated by contemporary launching campaigns to introduce pharmaceutical and technological innovations that are not backed up by sufficient proof of their advantages and safety.