Degludec linked to lower all-cause mortality than glargine in Swedish register

The study

This was a nationwide observational cohort study from Sweden. It used health registers, including the National Diabetes Register. The authors applied a target trial emulation approach, with longitudinal targeted minimum loss-based estimation to estimate average treatment effects.

People with type 2 diabetes who started insulin degludec or insulin glargine between 2012 and 2022 were included. Of 96 731 people identified, 44 890 met the eligibility criteria and were analysed.

Two cohorts were built. One reflected the eligibility criteria of the DEVOTE trial (trial-eligible). The other represented routine clinical practice (trial-ineligible). The primary outcome was major adverse cardiovascular events (MACE): myocardial infarction, stroke and cardiovascular mortality. Secondary outcomes were the individual parts of MACE, all-cause mortality and heart failure.

What they found

Trial-eligible cohort:

• MACE was not significantly different between degludec and glargine (risk ratio 1.10; 95% CI 0.91-1.34; p = 0.34).
• All-cause mortality was significantly lower with degludec (risk ratio 0.75; 95% CI 0.62-0.92; p = 0.002).

Trial-ineligible cohort:

• Degludec was associated with a lower risk of MACE (risk ratio 0.80; 95% CI 0.67-0.95; p = 0.004).
• Degludec was also associated with lower risks of all-cause mortality, cardiovascular mortality, non-fatal stroke and heart failure. The abstract does not give effect sizes for these outcomes.

The authors concluded that the lower all-cause mortality with degludec was seen in both cohorts, even though MACE was not significantly different in the trial-eligible cohort.

How much weight to give it

The authors present this as a nationwide real-world study. It is an observational cohort study, so it shows association, not cause. Patients were not randomised. People given degludec may differ from those given glargine in ways that the analysis did not capture. Residual confounding is always possible in observational data.

The pattern of results needs careful reading. In the trial-eligible cohort, MACE was not significantly different, yet all-cause mortality was lower with degludec. The abstract does not explain this. In the trial-ineligible cohort, degludec was associated with lower MACE risk.

The abstract does not report follow-up length, number of events, size of each cohort, how the groups differed at baseline, or funding. These details matter and should be checked in the full paper.

For your clinic

These results do not show that degludec should replace glargine to prevent death or cardiovascular events. They are an association from registry data.

Before using these findings to change practice, read the full paper. Check how confounding was handled, how the cohorts were defined and how long patients were followed. Also look at the DEVOTE trial itself and current guidelines.