by Prateek Chopra | June 23, 2026 | Diabetes Conferences | ADA 2026
Clinical Context
- The LEADER trial demonstrated that liraglutide reduced the risk of major adverse cardiovascular events (MACE) in individuals with type 2 diabetes (T2D) at high cardiovascular risk.
- This study examined whether these cardioprotective effects are observed in routine clinical practice among individuals who do and do not meet LEADER trial eligibility criteria.
Methods
- Data were obtained from the UK Clinical Practice Research Datalink (CPRD).
- Adults with T2D initiating either GLP-1 receptor agonists (GLP-1RA) or dipeptidyl peptidase-4 inhibitors (DPP4i) were included.
- Participants meeting LEADER eligibility criteria were assigned to a trial-matched cohort, while those not meeting the criteria formed a non-trial cohort.
- Longitudinal targeted maximum likelihood estimation (LTMLE) was used to evaluate 3-point MACE risk.
Study Population
- A total of 306,930 treatment initiators were identified.
- Trial-matched cohort: 23,401 participants.
- Non-trial cohort: 143,286 participants.
- Compared with the non-trial cohort, the trial-matched cohort was:
- Younger (60±13 vs 73±18 years).
- More likely to be female (49% vs 42%).
- Had lower HbA1c levels (71±17 vs 74±18 mmol/mol).
Cardiovascular Outcomes in the Trial-Matched Cohort
- At 3 years, the cumulative MACE risk was:
- 5.7% among GLP-1RA users.
- 7.1% among DPP4i users.
- Risk difference: –1.4%.
- Risk ratio: 0.80.
- These findings indicated a significant reduction in cardiovascular risk with GLP-1RA therapy.
Cardiovascular Outcomes in the Non-Trial Cohort
- At 3 years, the cumulative MACE risk was 3.4% in both treatment groups.
- Risk ratio: 1.0.
- No observable cardiovascular benefit was associated with GLP-1RA therapy in this population.
Clinical Implications
- Cardiovascular benefits of GLP-1RA therapy may be greatest among individuals whose clinical characteristics resemble those of participants enrolled in cardiovascular outcome trials.
- Careful patient selection may be important when applying trial findings to routine clinical practice.
GLP-1RA therapy was associated with a lower risk of major adverse cardiovascular events among individuals meeting LEADER trial eligibility criteria but not among those outside the trial population. These findings highlight the importance of considering patient characteristics when translating cardiovascular outcome trial evidence into real-world diabetes care.