SGLT2 inhibitor cardiac benefits extend to older people in real world
medwireNews: Sodium-glucose cotransporter (SGLT)2 inhibitors are associated with lower rates of heart failure hospitalization, all-cause mortality, and hypoglycemia, but higher rates of diabetic ketoacidosis (DKA), when compared with dipeptidyl peptidase (DPP)-4 inhibitors in older adults with type 2 diabetes, suggests a Canadian study.
The researchers compared data from 29,916 adults older than 65 years who received an SGLT2 inhibitor and the same number of propensity score-matched individuals taking a DPP-4 inhibitor.
They report that individuals who received an SGLT2 inhibitor were significantly less likely to experience the composite outcome of hospitalization for heart failure or all-cause mortality during follow-up than those given a DPP-4 inhibitor, at an adjusted hazard ratio (aHR) of 0.49. Only 584 people in the SGLT2 group experienced heart failure hospitalization or died (19 events per 1000 person–years), compared with 1390 adults in the DPP-4 inhibitor group (38 events per 1000 person–years), during a follow-up of 1.02 and 1.21 years, respectively.
Michael Fralick (University of Toronto, Ontario, Canada) and colleagues note that these results were influenced “to a greater extent” by the decrease in heart failure hospitalization than by the decrease in all-cause mortality risk.
They say that these findings were similar to those observed in the DAPA-HF and EMPEROR-Reduced trials, but the current study involved older people and “a past history of heart failure was rare,” suggesting that “the reduced risk of heart failure extends to older adults who are at a lower risk of heart failure hospitalization than those included in DAPA-HF and EMPEROR-Reduced.”
The data in the present study, covering new users of the drugs in Ontario, were obtained from the ICES drug database between 2015 and 2019; the mean age of the study population was 72 years and approximately 7% had a history of heart failure.
Fralick et al also found that individuals receiving SGLT2 inhibitors had lower rates of hypoglycemia (2.3 events per 1000 person–years) compared with individuals receiving DPP-4 inhibitors (3.9 events per 1000 person–years) at an aHR of 0.61.
However, people taking SGLT2 inhibitors were 1.84 times more likely to experience DKA during follow-up than those given DPP-4 inhibitors, at rates of 2.2 versus 1.2 events per 1000 person–years.
The authors then carried out a multivariable regression analysis to identify patient-level factors associated with adverse outcomes among individuals receiving an SGLT2 inhibitor, and observed that the “strongest factors” associated with heart failure or death risk were prior history of heart failure and prior history of cardiovascular disease, with an odds ratio (OR) of 5.83 and 1.65, respectively. Additionally, the strongest factors associated with DKA risk were glycated hemoglobin levels above 86 mmol/mol (10%) and prior insulin use, at an OR of 4.12 and 2.52, respectively.
Taken together, “[t]hese findings help to understand the risks and benefits of SGLT2 inhibitors in older adults and can inform clinical decision making until definitive evidence from a clinical trial of older adults is available” the team concludes in Diabetes, Obesity and Metabolism.
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