Faster aspart a favourable alternative to intensify T2D treatment

Intensive insulin titration with fast-acting insulin aspart (faster aspart) provided effective overall glycaemic control, superior post-prandial glucose (PPG) control, and a lower rate of severe or blood glucose (BG)-confirmed hypoglycaemia vs insulin aspart (IAsp), in combination with insulin degludec with or without metformin, in adults with advanced type 2 diabetes (T2D) not optimally controlled with a basal-bolus regimen, according to the ONSET 9 trial.

Individuals with long-standing T2D typically require basal insulin to control fasting hyperglycaemia. [Diabetes Res Clin Pract 2007;77:280-285] “[However, this is] often insufficient to achieve and maintain HbA_1c goals,” said the researchers, hence the need to add other alternatives* to intensify treatment targeting PPG. [Diabetes Care 2019;42:S90-S102]

Even without fasting hyperglycaemia, post-prandial hyperglycaemia is tied to adverse effects. [PLoS One 2016;11:e0168142; Neurology 2006;67:235-240] “[T]argeting PPG excursions is important for achieving overall glycaemic control and reducing the risk of the macrovascular and microvascular complications of diabetes,” noted the researchers.

Faster aspart is a novel formulation of IAsp with an earlier onset of action and a greater antihyperglycaemic effect in the first 30 minutes after dosing compared with IAsp. [Diabetes Obes Metab 2019;21:2068-2075] The ONSET 2 trial has shown the noninferiority of faster aspart to IAsp in terms of change from baseline HbA_1c. [Diabetes Care 2017;40:951-957]

This treat-to-target trial consisted of a 12-week run-in phase, a 16-week treatment phase, and a 30-day follow-up phase. A total of 1,091 participants (mean age 62 years, 51 percent male) with advanced T2D (>19 years) were randomized 1:1 to receive either faster aspart or IAsp delivered in a basal-bolus regimen, with insulin degludec QD with or without metformin. [Diabetes Care 2020;43:1710-1716]

At the end of treatment phase, noninferiority for the HbA_1c change from baseline was confirmed for faster aspart vs IAsp (estimated treatment difference [ETD], –0.04 percent; p_{noninferiority}<0.001).

Using a meal test, 1-hour PPG increment was markedly improved with faster aspart vs IAsp (ETD, –0.40 mmol/L; p_superiority=0.001). “[This implies] that improvement in mealtime glucose control can be achieved in this clinically challenging population,” said the researchers.

Self-measured 1-hour PPG increment was also greater with faster aspart vs IAsp for the overall main meal (ETD, –0.25 mmol/L; p=0.003), lunch (ETD, –0.32 mmol/L; p=0.012), and main evening meal (ETD, –0.27 mmol/L; p=0.03).

These findings are reinforced by a significantly greater increase in 1,5-anhydroglucitol with faster aspart vs IAsp (ETD, 0.50 µg/mL; p=0.012).

Overall rate of treatment-emergent severe or BG-confirmed hypoglycaemia was significantly lower with faster aspart vs IAsp (estimated treatment ratio [ETR], 0.81; p=0.019), as were the daytime (ETR, 0.83; p=0.038) and nocturnal rates (ETR, 0.66; p=0.004).

“Hypoglycaemia often impedes the achievement of optimal glycaemic control in patients with T2D treated with insulin … These findings demonstrate that these next-generation insulins – faster aspart and insulin degludec – can provide important clinical value in tailoring of complex basal-bolus regimens to limit the incidence of hypoglycaemia for patients with advanced T2D,” said the researchers.

“[Taken] together, these findings are encouraging, given that patients with advanced T2D … treated with a basal-bolus regimen represent a difficult patient population to manage, with PPG control being particularly challenging,” they added.