Estimated life-years free of CVD with GLP-1RA in patients with T2DM

Estimated Life-Years Gained Free of New or Recurrent Major Cardiovascular Events With the Addition of Semaglutide to Standard of Care in People With Type 2 Diabetes and High Cardiovascular Risk

Literature - Westerink J, Matthiessen KS, Nuhoho S, et al., - Diabetes Care 2022, doi:10.2337/dc21-1138

Introduction and methods

//Background//

To estimate absolute life expectancy free of new/recurrent CVD events gained with an intervention, competing risk-adjusted lifetime risk models combined with HRs from trial can be used at an individual level. The estimated individual benefit that a patient may gain from treatment can be discussed with the patient, thereby improving shared decision-making.

The lifetime risk prediction tool for patients with T2DM is the Diabetes Lifetime-perspective prediction (DIAL) risk model and is available at http://www.u-prevent.com [1].

The GLP-1RA semaglutide improved CV outcomes in patients with T2DM at high risk of CVD in a pooled analysis [2] of the SUSTAIN 6 [3] and PIONEER 6 trials [4]. In this pooled analysis, CV risk reduction with semaglutide was expressed as relative risk based on the average patient from these trials.

This study estimated the effect of adding semaglutide to standard of care on life-years free of new/recurrent CVD events in patients with T2DM, using the DIAL model and pooled baseline characteristics data from SUSTAIN 6 and PIONEER 6 (POOLED cohort; n=6480).

Methods

For every individuals in the POOLED cohort life expectancy free of new/recurrent CVD events and 10-year CVD risk was estimated using the yearly patient-level risk of MACE and noncardiovascular mortality, derived from the DIAL model. Life-years free of new/recurrent CVD events were calculated as difference between baseline age and age at which the estimated cumulative probability of survival free from MACE first falls below 50%. 10-Year CVD risk was calculated as the sum of the yearly risk of MACE over 10 years.

The HR for MACE of 0.76 from SUSTAIN 6 and PIONEER 6 was applied to the yearly risk of MACE on an individual level to estimate individual treatment benefit.

Outcomes

Key outcomes were absolute gain in life-years free of new/recurrent CVD events, defined as life-years free of new or recurrent MACE, and 10-year CVD risk, defined as 10-year risk of new or recurrent MACE.

Main results

CV benefit with semaglutide

Using the DIAL model, analysis showed that treatment with semaglutide was associated with a wide distribution in life-years free of new/recurrent CVD events gained in the POOLED cohort, with a mean increase of 1.7 (95%CI:0.5-2.9) life-years.
Mean absolute reduction in 10-year CVD risk was 6.0% (95%CI:1.9-10.0), with a NNT of 16.6 and mean relative risk reduction of 19.9%.

Effect of baseline risk on CVD benefit with semaglutide

Patients with established CVD had a higher baseline risk of CVD events and larger gains in life-years free of new/recurrent CVD events with semaglutide treatment (2.0 years) compared with patients with CV risk factors (0.2 years). Both groups had wide distributions in life-years free of new/recurrent CVD events gained.
Patients with CKD had a gain in life-years free of new/recurrent CVD events of 1.7 years, with a wide distribution.
Mean absolute reduction in 10-year CV risk was 6.8% (RRR 19.4%) in patients with established CVD, 0.8% (RRR 23.7%) in patients with CV risk factors and 8.5% (RRR 17.1) in patients with CKD.

Effect of age on CVD benefit with semaglutide

Mean number of life-years free of new/recurrent CVD events gained with semaglutide treatment decreased with increasing age in patients with established CVD, from 2.9 years in patients 50-54 years to 0.6 years in patients aged 85-90 years.
A similar trend was seen in the subgroup of patients with CV risk factors or CKD, although to a lesser extent.

Conclusion

This study showed that treatment with semaglutide resulted in gain in life-years free of new/recurrent CVD events and a decrease in 10-year CVD risk in patients with T2DM. There was a wide distribution of estimated life-years free of new/recurrent CVD events gained with semaglutide, which reflects variation between patients. Patients with higher baseline CV risk and who were younger at treatment initiation had the greatest absolute benefit.

The authors state: “This study helps to contextualize the results of cardiovascular outcomes trials of use of semaglutide and can be used to aid in clinical decision-making.”

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