Researchers compare the cardiovascular effectiveness and safety of GLP-1 agonists and SGLT-2 inhibitors in older adults with diabetes.
Both sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP1RA) have been shown to have cardiovascular benefits in patients less than 65 years old. Current guidelines recommend initiating a GLP1RA or SGLT2i in patients with a high risk for cardiovascular disease, established ASCVD, chronic kidney disease (CKD), or heart failure. However, the effectiveness and safety have not been evaluated in geriatric patients, who compose most patients with type 2 diabetes. Older adults may have a higher incidence of adverse effects or altered outcomes due to polypharmacy, functional alterations due to aging, and comorbidities. Therefore, a cohort study was conducted to assess the cardiovascular effectiveness and safety in older adults with type 2 diabetes.
Researchers from Brigham and Women’s Hospital and Harvard Medical School in Boston, Massachusetts, identified 90,094 patients utilizing Medicare data from April 2013 to December 2016. Patients were included in the study if they were 66 years or older, had a diagnosis of type 2 diabetes, and were on either an SGLT2i (canagliflozin, dapagliflozin, or empagliflozin) or GLP1 RA (albiglutide, dulaglutide, exenatide, or liraglutide). The study’s two primary outcomes were major adverse cardiovascular events (MACE), including myocardial infarction, stroke, cardiovascular death, and hospitalization for heart failure. The safety outcomes evaluated were risks of diabetic ketoacidosis, genital infections, fractures, lower-limb amputations, acute kidney injury, severe urinary tract infections, and mortality. An exposure propensity score (PS) was calculated to control differences in the baseline patient characteristics using a multivariable logistic regression model. An “intention-to-treat” analysis was mimicked, and subgroup analyses were conducted by age (66-74 years and 75+ years), use of metformin, and history of CKD.
Results of the study found that SGLT2i had similar rates of MACE (HR 0.98 [95% CI, 0.87 – 1.10]) and lower rates of hospitalization for heart failure (HR 0.68 [95% CI 0.57 – 0.80]) when compared to GLP1RA. Furthermore, there were differences between incidence of myocardial infarction (HR 0.98, [95% CI, 0.84 -1.16]), incidence of stroke (HR 1.04, [95% CI, 0.86 -1.27]), cardiovascular mortality (HR 0.83, [95% CI, 0.64-1.07]). Safety outcomes reported a 46% increase in diabetic ketoacidosis risk (HR 1.46, [95% CI, 1.02 – 2.07]), 44% increase in lower limb amputation risk (HR 1.44, [95% CI, 1.06-1.96]), 3.4-fold increase in genital infection risk (HR 3.34, [95% CI, 3.08 – 3.62]), and 15% decrease in acute kidney injury risk (HR 0.85, [95% CI, 0.79 – 0.92]), with SGLT2i use. The risk of bone fractures and severe urinary tract infections did not differ between SGLT2i and GLP1RA. No difference was also noted in the subgroup analysis results according to age, metformin use, and CKD history. However, patients with a CVD history had reductions in hospitalization for heart failure risk, cardiovascular death risk, and all-cause mortality with SGLT2i use compared to GLP1RA.
This study’s limitations relate to the PS matching inability to adjust for all baseline characteristics, resulting in imbalances between both groups. Furthermore, the higher use of canagliflozin and liraglutide than other SGLT2i and GLP1RA agents may affect generalizability to other medications used in these drug classes. Adverse safety effects associated with GLP1RA, such as acute pancreatitis and acute gallbladder/biliary disease, were also not evaluated, preventing a proper benefit-risk assessment in older adults. Future studies can include GLP1RA specific safety issues and have a more comprehensive SGLT2 and GLP1RA agents range. Overall, SGLT2i were associated with similar incidences of MACE, lower hospitalization rates for heart failure and an increased cardiovascular benefit in patients with a history of CVD compared to GLP1RA use.
- In older adults with type 2 diabetes, SGLT2i use had similar MACE incidence and lower hospitalization for heart failure than GLP-1 RA.
- SGLT2i was associated with a greater risk of diabetic ketoacidosis, amputation risk, genital infection risk, and a lower risk of acute kidney injury, with no differences in fractures and urinary tract infections.
- Future studies will need to explore GLP-1 RA specific adverse events in older adults /geriatric population to determine incidence and guide antihyperglycemic drug initiation.
Patorno E, Pawar A, Bessette LG, et al. Comparative Effectiveness and Safety of Sodium-Glucose Cotransporter 2 Inhibitors Versus Glucagon-Like Peptide 1 Receptor Agonists in Older Adults. Diabetes Care. 2021.
Macrina Ghali, PharmD Candidate 2021, Florida A&M University, College of Pharmacy and Pharmaceutical Sciences