This retrospective study used real-world data to estimate the impact of SGLT2 inhibitors and GLP-1 receptor agonists, used singly or in combination with each other, on all-cause mortality and cardiorenal outcomes in people with type 2 diabetes. Data from 2010 to 2023 were obtained from TriNetX, a collaborative health research network spanning 14 countries, with most participants living in the US.
Data on approximately 186 000 GLP-1 RA recipients, 143 000 SGLT2 inhibitor recipients and 108 000 recipients of the two drug classes combined were compared with 1.8 million individuals who received neither drug. Participants were propensity-score-matched for age, gender, ischaemic heart disease, hypertension, heart failure, chronic kidney disease (CKD) and HbA1c.
In the survival analysis, over 5 years, SGLT2 inhibitors reduced the risk of all-cause mortality by 51%. Hospitalisation, myocardial infarction, angina, heart disease, heart failure, atrial fibrillation, stroke, lower limb amputation and CKD were also reduced by 9–31%. GLP-1 RAs reduced the risk of all-cause mortality by 53% and cardiorenal outcomes by 10–34%.
Combining the two therapies resulted in a 75% reduction in all-cause mortality and 16–41% reductions in cardiorenal outcomes. When comparing combination with individual therapies, significant reductions in mortality and cardiorenal outcomes were observed.
While acknowledging the limitations of the retrospective design and a potential lack of data completeness in this real-world database, the authors conclude that SGLT2 inhibitors and GLP-1 RAs are more effective than other diabetes medications in terms of preventing mortality, cardiovascular and renal outcomes in people with type 2 diabetes, and that combining the therapies has additive benefits. These findings should be confirmed in randomised controlled trials of monotherapy versus combination therapy.