A review of human and analogue insulin trials☆

Abstract 

A recent meta-analysis evaluated trials of the rapid-acting analogues insulin lispro and insulin aspart, performed before the introduction of the basal analogues, insulin glargine and insulin detemir. This article reviews the effect of rapid-acting and basal insulin analogues separately and in combination, relative to human insulin. Outcomes evaluated include HbA_1c, hypoglycaemia, postprandial glucose (PPG), and weight changes. Results from trials that matched defined criteria are presented in tables. In type 1 diabetes, compared with human insulin, the rapid-acting analogues generally reduced hypoglycaemia and postprandial glucose, whereas the basal analogues tended to reduce hypoglycaemia – particularly nocturnal hypoglycaemia. Weight gain may also be reduced with basal analogues, compared with human basal insulin. In type 2 diabetes, premix rapid-acting analogues controlled postprandial glucose better than human insulin mixes; basal analogues used as basal-only therapy reduced hypoglycaemia compared with NPH insulin; and some advantages were apparent with analogues in basal-bolus therapy. Whilst the benefits on individual metabolic and clinical outcomes appear modest, almost all studies report some advantage when using insulin analogues in type 1 and type 2 diabetes. Significant benefits, including PPG lowering with the rapid-acting analogues and the potential for reduction in cardiovascular risk, should be investigated further.

Abbreviations: AACE, American Association of Clinical Endocrinologists, AUC, area under the curve, BG, blood glucose, BHI, premix human insulin, BIAsp, premix insulin aspart, bid, twice daily, FBG, fasting blood glucose, FPG, fasting plasma glucose, HI, human insulin, IAsp, insulin aspart, IDet, insulin detemir, IGlarg, insulin glargine, IGlu, insulin glulisine, ILis, insulin lispro, Mix25, premix insulin lispro, NPH, NPH insulin, NS, not significant, OADs, oral antidiabetic agents, od, once daily, PG, plasma glucose, PPG, postprandial glucose, RR, relative risk, SM, self-monitored

Keywords: Insulin analogues, Hypoglycaemia, Postprandial glucose