These second-generation basal insulin analogs, Gla-300 and IDeg-100, also had similar safety profiles, investigators found.
A new study of second-generation basal insulin analogs shows insulin glargine (Lantus) is noninferior to insulin degludec (Tresiba) compared with the time patients with type 1 diabetes (T1D) spend within their target glucose ranges.The study also marks the first time that continuous glucose monitoring (CGM)-based time in range (TIR) has been used as the primary efficacy end point in a randomized comparison of second-generation glucose analogs.
The report was published in Diabetes, Obesity and Metabolism.
The authors explained that CGM has become an increasingly common method of achieving metabolic control in people with T1D. The technology also makes it possible to more comprehensively understand how long a patient spends within their target glucose range, they added. CGM has therefore become increasingly important in evaluating the efficacy of therapy in trials of people with T1D.
Second-generation basal insulin analogs, like insulin glargine 300 U/mL (Gla-300) and insulin degludec 100 U/mL (IDeg-100) have been shown to outperform earlier-generation insulin analogs, providing stable, prolonged outcomes. However, the investigators said there has not yet been a study that compared those insulin analogs using CGM as a primary or secondary end point.
The new study, called InRange, is the first to do so. In the study, 343 adults with T1D were randomly assigned to receive either Gla-300 or IDeg-100 for 12 weeks. The study mandated that patients had to be treated with multiple daily injections, with basal insulin once daily and rapid-acting insulin analogs for at least 1 year. Patients also needed to have hemoglobin A1C levels between 7% and 10% upon screening.
The enrollees were split between Gla-300 and IDeg-100 on a 1:1 basis, with a primary end point of noninferiority of Gla-300 vs IDeg-100, based on percentage of time within the range of 70 to 180 mg/dL.
After 12 weeks, the investigators said the data showed Gla-300 performed similarly to IDeg-100.
“The least squares [LS] mean estimates for TIR at week 12 were 52.74% (95% CI, 51.06%-54.42%) for Gla-300 and 55.09% (95% CI, 53.34%-56.84%) for IDeg-100,” the authors reported. “LS mean difference (noninferiority) was 3.16% (95% CI, 0.88%-5.44; noninferiority P = .0067).”
The finding was confirmed by glucose total coefficient variation, which similarly showed that Gla-300 was noninferior to IDeg-100.
“Occurrences of self-measured and CGM-derived hypoglycemia were comparable between treatment groups,” the authors found. “Safety profiles were consistent with known profiles, with no unexpected findings.”
They noted limitations to their study. Among them was the open-label design, which they said was necessary since the pens used to administer the 2 medications are different and thus distinguishable. They also noted that their 12-week treatment period was shorter than some other clinical trials.
“While the CGM data collection period in InRange was of a length that has been shown to provide data that correlate with long-term (3-month) glycemic outcomes, longer-term CGM data would provide more robust conclusions,” they wrote.
Still, the investigators said their data show that Gla-300 holds up well against IDeg-100, both in terms of TIR and safety.
“Using clinically relevant CGM metrics, InRange demonstrates that Gla-300 is noninferior to IDeg-100 in people with T1D, with comparable hypoglycemia and safety profiles,” they concluded.
Battelino T, Danne T, Edelman SV, et al. CGM-based time-in-range using insulin glargine 300 units/mL versus insulin degludec 100 Units/mL in type 1 diabetes: the head-to-head randomized controlled InRange trial. Diabetes Obes Metab. Published online October 20, 2022. doi:10.1111/dom.14898