Once-weekly insulin as good as once-daily dose?

Insulin icodec, an in-development basal insulin analogue administered once weekly, was as effective as once-daily insulin glargine in patients with type 2 diabetes (T2D) insufficiently controlled with metformin with or without a DPP-4* inhibitor, according to a phase II trial presented at EASD 2020.

“[T]he use of [once-weekly] icodec resulted in glycaemic control similar to that of once-daily glargine without significantly affecting rates of clinically relevant hypoglycaemia [in this population],” noted the researchers.

This multinational, double-blind, placebo-controlled study comprised 247 insulin-naïve** adults (mean age 59.6 years, 56.3 percent male) with T2D inadequately controlled with metformin with or without a DPP-4 inhibitor (HbA_1c 7.0–9.5 percent; mean 8.02 percent). They were randomized 1:1 to receive once-weekly insulin icodec (initial dose 70 U QW) or once-daily insulin glargine U100 (initial dose 10 U QD) subcutaneously for 26 weeks, with doses adjusted weekly to achieve a 70–108 mg/dL pre-breakfast target.

At week 26, recipients of both insulin types experienced HbA_1c reductions from baseline (estimated mean change, -1.33 and -1.15 percentage points in icodec and glargine recipients, respectively), with no difference between groups (estimated between-group difference, -0.18 percentage points, 95 percent confidence interval [CI], -0.38 to 0.02; p=0.08). [EASD 2020, abstract 56; N Engl J Med 2020;doi:10.1056/NEJMoa2022474]

At week 26, 72 and 68 percent of the icodec and glargine recipients, respectively, achieved HbA_1c <7 percent (estimated odds ratio [OR], 1.20), while 49 and 39 percent, respectively, achieved HbA_1c ≤6.5 percent (estimated OR, 1.47).

Change in fasting plasma glucose levels between baseline and week 26 did not differ between icodec and glargine recipients (mean, -57.74 vs -53.86 mg/dL; difference, -3.9), nor did change in body weight (mean, 1.49 vs 1.56 kg; difference, -0.08).

Icodec recipients had a greater reduction in 9-point patient-measured blood glucose profile from baseline to week 26 than glargine recipients (mean, -48.63 vs -40.77 mg/dL; difference, -7.86).

In the last 2 weeks of treatment, icodec recipients spent more time within tight glycaemic range (70–140 mg/dL) than glargine recipients (estimated mean, 66.11 percent vs 60.71 percent).

“[This corresponded] approximately to an extra 78 minutes spent in the target glycaemic range per day in the icodec group,” the researchers said.

Weekly insulin dose was lower in icodec vs glargine recipients (estimated mean, 229.06 vs 284.05 U/week).

Four and seven icodec and glargine recipients, respectively, discontinued treatment, and one and two, respectively, initiated ancillary treatment***.

Adverse events (AEs) up to week 31 affected a similar proportion of icodec and glargine recipients (52.0 percent vs 50.8 percent), with two and three patients, respectively, experiencing serious AEs, though none of the serious AEs were deemed possibly or probably insulin related. Injection-site reactions were rare and were mild and rapidly resolved.

Rates of level 2 hypoglycaemia (blood glucose <54 mg/dL) and level 3 hypoglycaemia (severe cognitive impairment requiring assistance) were low, and comparable between groups (0.53 vs 0.46 events per patient-year in the icodec vs glargine group; estimated rate ratio, 1.09, 95 percent CI, 0.45–2.65).

“Insulin icodec had a favourable side effect profile, and no unexpected safety findings occurred,” the researchers said.

“The findings … suggest that once-weekly insulin has the potential to facilitate insulin management, providing clinical benefits and reducing the number of injections per year from 365 to 52,” they said. There is also the potential for improved treatment satisfaction, adherence, and persistence.

Despite the positive results, the researchers cautioned that the trial was not powered to detect significant between-group differences for any of the endpoints.