Clinical Pearls & Morning Reports
Published July 26, 2023
Rosenstock et al. conducted a trial that investigated the efficacy and long-term safety of once-weekly insulin icodec as compared with once-daily insulin glargine U100, both in combination with noninsulin glucose-lowering treatments, in persons with type 2 diabetes who had not previously received insulin. Read the NEJM Original Article here.
Q: What is insulin icodec?
A: Insulin icodec is an investigational once-weekly basal insulin analogue for diabetes management. A short-term, proof-of-concept, phase 2 trial involving persons with type 2 diabetes who had not previously received insulin compared once-weekly insulin icodec with once-daily insulin glargine U100 and showed similar glycemic control and low rates of hypoglycemia in the two trial groups.
Q: Was icodec associated with a greater decline in the glycated hemoglobin level than glargine U100 from baseline to week 52 in the trial by Rosenstock et al.?
A: The primary trial end point was the absolute change in the glycated hemoglobin level (in percentage points) from baseline to week 52. The estimated mean change in the glycated hemoglobin level from baseline to week 52 was -1.55 percentage points with icodec and -1.35 percentage points with glargine U100, with an estimated treatment difference of -0.19 percentage points (95% confidence interval [CI], -0.36 to -0.03), which confirmed the noninferiority (P<0.001) and superiority (P = 0.02) of icodec. At the end of the extension phase (week 78), the reduction in glycated hemoglobin level with icodec was sustained.
A: In weeks 48 to 52, participants receiving icodec spent a significantly greater percentage of time in the target glycemic range than those receiving glargine U100 (71.9% vs. 66.9%; estimated treatment difference, 4.27 percentage points [95% CI, 1.92 to 6.62]; P<0.001), which translated to approximately 1 hour and 1 minute additional time spent in range per day. No significant difference was detected in the percentage of time spent with glucose levels of less than 54 mg per deciliter at weeks 48 to 52 with icodec or glargine U100 (estimated treatment ratio, 1.27; 95% CI, 0.94 to 1.71). There was no evidence of a substantial difference in the estimated mean change in body weight from baseline to week 52: 2.29 kg with icodec and 1.83 kg with glargine U100 (estimated treatment difference, 0.46 kg; 95% CI, −0.12 to 1.04).
A: Although the rate of clinically significant or severe hypoglycemic episodes differed at week 83, with slightly more in the icodec group than in the glargine U100 group, overall rates of these hypoglycemic episodes remained below one event per person-year of exposure throughout the trial, which is similar to rates reported previously in other trials of daily basal insulin analogues involving patients with type 2 diabetes who had not previously received insulin. From baseline to week 83, a total of 226 clinically significant hypoglycemic events occurred in 61 participants (12.4%) receiving icodec, as compared with 114 events in 66 participants (13.4%) receiving glargine U100. Moreover, at weeks 52 and 78, more participants receiving icodec than those receiving glargine U100 reached a glycated hemoglobin level below 7% without clinically significant or severe hypoglycemia in the preceding 12 weeks. Only 1 episode of severe hypoglycemia occurred with icodec and 7 with glargine U100 during this 18-month trial.