Evidence Matters

RCT Results: Once-Weekly vs Once-Daily Insulin for Type 2 Diabetes

BACKGROUND AND PURPOSE:

Rosenstock et al. (NEJM, 2023) investigated the efficacy and long-term safety of once-weekly insulin icodec vs once-daily insulin glargine U100 in persons with type 2 diabetes

Randomized, open-label phase 3a trial
- 52-week main phase | 26-week extension phase | 5-week follow-up
Participants
- ≥18 years Type 2 diabetes: Glycated hemoglobin level, 7 to 11%
- Not previously received insulin
Interventions
- Once-weekly insulin icodec (700 U per milliliter)
- Once-daily insulin glargine U100 (100 U per milliliter)
Study design
- 1:1 randomization
- Medication given subQ
- Starting dose
  - Icodec: 70 U per week
  - Glargine U100: 10 U per day
- Treat-to-target trial
  - Insulin doses adjusted to target prebreakfast self-measured blood glucose target of 80 to 130 mg per deciliter (4.4 to 7.2 mmol per liter)
- Hypoglycemic episodes (from baseline to weeks 52 and 83) were recorded
Primary outcome
- Change in the glycated hemoglobin level from baseline to week 52
Secondary outcome
- Percentage of time spent in the glycemic range of 70 to 180 mg per deciliter (3.9 to 10.0 mmol per liter) in weeks 48 to 52

Once-weekly: 492 participants | Once-daily: 492 participants
- Baseline characteristics were similar between the 2 groups
Mean reduction in the glycated hemoglobin level at 52 weeks was greater with icodec
- Icodec: 8.50% to 6.93% | Mean change −1.55 percentage points
- Glargine U100: 8.44% to 7.12% | Mean change −1.35 percentage points
- Estimated between-group difference: −0.19 (95% CI, −0.36 to −0.03) percentage points
- Noninferiority: P<0.001 | Superiority of icodec: P=0.02
Percentage of time spent in the glycemic range of 70 to 180 mg per deciliter was significantly higher with icodec
- Icodec: 71.9% | Glargine U100: 66.9%
- Estimated between-group difference: 4.27 (95% CI, 1.92 to 6.62) percentage points
- Superiority: P<0.001
Rates of combined clinically significant or severe hypoglycemia similar between the groups
- At week 52
  - Icodec: 0.30 events per person-year of exposure
  - Glargine U100: 0.16 events
  - Estimated rate ratio (RR) 1.64 (95% CI, 0.98 to 2.75)
- At week 83
  - Icodec: 0.30 events per person-year of exposure
  - Glargine U100: 0.16 events
  - Estimated RR 1.63 (95% CI, 1.02 to 2.61)
Safety
- There were no new safety signals detected
- Incidences of adverse events were similar between the two groups

For patients with type 2 diabetes, better glycemic control was achieved with once-weekly insulin icodec compared to once-daily insulin glargine U100