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Newer Glucose-Lowering Drugs Reduce CV Events in Older Adults

"Use of GLP1-RAs and SGLT-2is was associated with reduced rates of 3P-MACE and HHF compared to DPP-4is, independent of age" - findings from a Danish nationwide study of 35,679 patients aged 70 and older with T2D.

Conexiant

In a nationwide Danish target trial emulation cohort study, newer glucose-lowering drugs—sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide 1 receptor agonists—were associated with lower risks of cardiovascular events and heart failure hospitalization compared to dipeptidyl peptidase 4 inhibitors among adults aged 70 and older with type 2 diabetes.

Published in eClinicalMedicine, the study included 35,679 individuals who initiated one of the three medications between 2012 and 2020, with follow-up through December 2021. Using data from Danish national health registers, researchers emulated a three-arm randomized trial and applied summarized weights based on inverse probability weighting to balance baseline characteristics and treatment adherence.

In the as-treated analysis, both glucagon-like peptide 1 receptor agonists (GLP1-RAs) and sodium-glucose cotransporter 2 inhibitors (SGLT-2is) were associated with significantly lower rates of three-point major adverse cardiovascular events (3P-MACE)—a composite of myocardial infarction, stroke, and all-cause mortality—compared with dipeptidyl peptidase 4 inhibitors (DPP-4is). The incidence rate ratio (IRR) for 3P-MACE was 0.68 (95% CI, 0.65–0.71) for GLP1-RAs and 0.65 (95% CI, 0.63–0.68) for SGLT-2is. For hospitalization due to heart failure (HHF), the IRRs were 0.81 (95% CI, 0.74–0.88) and 0.60 (95% CI, 0.55–0.66), respectively.

The researchers noted that these cardiovascular benefits were predominantly independent of age, though some age-specific variations were observed, particularly for HHF in patients over 85 years.

When comparing SGLT-2is directly with GLP1-RAs, no significant difference was observed in 3P-MACE (IRR 0.96; 95% CI, 0.91–1.01), although SGLT-2is were associated with fewer heart failure hospitalizations (IRR 0.75; 95% CI, 0.67–0.83).

Analysis of individual cardiovascular outcomes revealed that both GLP1-RAs and SGLT-2is were linked to lower all-cause mortality and stroke rates than DPP-4is. SGLT-2is were additionally associated with reduced myocardial infarction rates (IRR 0.89; 95% CI, 0.80–0.99), a benefit not observed with GLP1-RAs (IRR 0.97; 95% CI, 0.87–1.08).

Subgroup analysis also found similar patterns in individuals with and without cardiovascular disease (CVD) at baseline. GLP1-RAs were associated with reduced rates of HHF in individuals with CVD at initiation (IRR 0.77; 95% CI, 0.70–0.84), but showed a higher rate of HHF in participants without preexisting CVD (IRR 1.30; 95% CI, 1.01–1.67).

To evaluate the robustness of their findings, researchers conducted five sensitivity analyses: using overlap weights instead of IPW, shortening the washout period for non-fatal outcomes, excluding participants who experienced outcomes within 90 days of initiation, including HbA1c measurements as covariates, and using an as-started approach. Results remained consistent across these models.

While the study provided detailed comparative effectiveness data, it did not assess safety outcomes. The authors concluded that these findings may help strengthen implementation of current guidelines for cardiovascular risk reduction in older adults with type 2 diabetes.

Vanja Kosjerina from the Steno Diabetes Center Copenhagen and the Department of Endocrinology at University Hospital Bispebjerg-Frederiksberg led the study. No external funding was reported. Some co-authors disclosed employment or equity ties with Novo Nordisk A/S.