Review: Rapid-acting analogues do not differ from regular human insulin for mortality or HbA1c in type 2 diabetes

The review shows that, contrary to specialty recommendations, there is no reason not to use regular human insulins, which are less costly than analogue insulins, said an ACP Journal Club commentary.


There are no clear benefits of short-acting insulin analogues over regular human insulin (RHI) in people with type 2 diabetes, according to a recent review. It included 10 randomized controlled trials (RCTs) that compared the two types of insulin for at least 24 weeks. The review found that overall the evidence was poor, with none of the trials designed to investigate long-term effects, such as mortality or complications. No significant difference in glycemic control between insulin types was found.

The review was published by the Cochrane Library on Dec. 17, 2018. The following commentary by Mayer B. Davidson, MD, was published in the ACP Journal Club section of the April 16 Annals of Internal Medicine.

The recent Cochrane review by Fullerton and colleagues found that rapid-acting analogue insulins did not reduce HbA1c more than RHI. The quality of some of the included trials may be questionable, but the results are similar to those of a 2014 report that found that 7 of 9 RCTs of patients with type 2 diabetes showed no difference in HbA1c between analogue insulins and RHI.

These results are in contrast to the repeated recommendations from specialty organizations and specialists to use analogue insulins. Why? Perhaps it is based on the small pharmacokinetic and pharmacodynamic differences between analogue insulins and RHIs. However, with 20% to 30% intraindividual day-to-day variability in response to insulin, these minor pharmacokinetic–pharmacodynamic differences are clinically irrelevant. For instance, most of us were taught that RHI should be injected 20 to 30 minutes before a meal. However, a crossover study revealed no difference in glucose levels for 6 weeks after regular insulin was given either 20 minutes or just before meals.

The cost of insulin tripled from 2001 to 2010 and doubled yet again between 2012 and 2016, with analogue insulins costing ≥2.5 times as much as RHI in the USA. Because of these increased costs, 25% of patients who require insulin are not taking the full amount of their prescribed doses. The results of the review by Fullerton and colleagues show that there is no reason not to use RHIs, which are less costly than analogue insulins.