Faster-acting insulin aspart: useful, but not an ideal pump insulin

Faster-acting insulin aspart (Fiasp) has been developed to address shortcomings in existing rapid-acting insulin analogues, including insulin aspart itself, and thus reduce prandial glucose excursions. When first introduced it was claimed that rapid-acting analogues had a sufficiently quick onset of action that they could be given at the start of a meal or even once the meal had been eaten. It is now clear that for optimal prandial glucose control, bolus doses of these rapid-acting analogue insulins should be given at least 15–20 minutes before a meal, even when delivered by an insulin pump. Furthermore, there are some individuals who find that when they use the existing rapid-acting analogues in this way to control the post-prandial peak, they frequently suffer late post-prandial hypoglycaemia. The ideal rapid-acting insulin would be effective when given immediately before the meal and would reduce the risk of post-prandial hypoglycaemia compared to existing bolus insulins.
 
Fiasp is a mixture of insulin aspart and niacinamide, which accelerates the absorption of insulin aspart. When given by subcutaneous injection, Fiasp has a faster onset of action and a greater early glucose-lowering effect than conventional insulin aspart. The ‘Onset’ studies have investigated the efficacy of Fiasp. In Onset 1, Fiasp given at the start of meals resulted in a greater glucose-lowering effect and reduction in HbA_1ccompared to insulin aspart when both were used in multiple daily injection regimens containing insulin detemir (Russsell-Jones et al, 2017). 
 
Klonoff et al (2019) now report the results of the Onset 5 study, summarised in our Digest here, comparing Fiasp with insulin aspart used in insulin pump therapy in people with type 1 diabetes. All participants used Medtronic insulin pumps and gave mealtime bolus insulin at the start of the meal (0–2 minutes pre-meal). As expected, those using Fiasp had a reduction in 1-hour post-prandial glucose level of just under 1 mmol/L, consistent with its more rapid onset of action and greater early glucose-lowering effect. However, there was no difference in HbA_1c seen between the groups and there was a higher frequency of severe hypoglycaemia in the first hour after the start of the meal in those using Fiasp. The authors speculate on the lack of HbA_1c improvement with Fiasp and note that Fiasp users had higher nocturnal and pre-meal blood glucose levels, which may have offset the benefit seen in post-prandial glucose lowering.
 
It is disappointing that Fiasp does not show clear superiority over insulin aspart when used in an insulin pump. One of the advantages of insulin pump therapy is the more reliable, consistent circulating insulin profiles achieved with a continuous infusion of low doses of rapid-acting analogue insulin. An improved rapid-acting insulin analogue might be expected to result in even better outcomes with insulin pump therapy; therefore does Fiasp not represent an improvement? And does it have a role for those using insulin pump therapy?
 
The Onset 5 trial did not select any particular group of pump users, and it is clear that switching to Fiasp is unlikely to be the answer for all those using insulin pump therapy who are unable to achieve the glycaemic control they are looking for. Indeed, it is possible that Fiasp – as a result of its different pharmacokinetics – may be inferior to existing rapid-acting analogues for basal insulin delivery via pump, which could account for the improved HbA_1c with Fiasp added to insulin detemir in Onset 1, but not when used in a pump in Onset 5. 
 
Fiasp should be of particular benefit for those pump users who cannot optimise control as a result of high post-prandial glucose excursions and/or suffer late post-prandial hypoglycaemia when they try to do so, particularly if they are already giving their boluses 15–20 minutes before meals. Meanwhile, the search for the ideal pump insulin continues.
 
Click the links below to access the latest Diabetes Digests related to devices:

• Faster-acting insulin aspart non-superior to aspart in pump therapy
• CGM with remote monitoring in children improves parents’ quality of life
• Switching from flash to continuous glucose monitoring reduces hypoglycaemia risk
• Glucose-sensor-based app improves type 1 diabetes management

References
Klonoff DC, Evans ML, Lane W et al (2019) A randomized, multicentre trial evaluating the efficacy and safety of fast-acting insulin aspart in continuous subcutaneous insulin infusion in adults with type 1 diabetes (onset 5).  Diabetes Obes Metab 21: 961–7
Russell-Jones D, Bode BW, de Block C et al (2017) Fast-acting insulin aspart improves glycemic control in basal-bolus insulin treatment for type 1 diabetes: results of a 26-week multicenter, active-controlled, treat-to-target randomized, parallel-group trial (onset 1). Diabetes Care 40: 943–50