Evaluating the Safety of Sodium-Glucose Cotransporter-2 Inhibitors in a Nationwide Veterans Health Administration Observational Cohort Study.

Sodium-glucose cotransporter-2 inhibitors (SGLT-2is) are indicated in patients with or without type 2 diabetes mellitus atherosclerotic cardiovascular disease, chronic kidney disease, or heart failure. Postmarket surveillance data have identified many safety signals which warrants further investigation. We aimed to compare the safety of SGLT-2i and glucagon-like peptide-1 receptor agonists (GLP-1RA). Using the Veterans Health Administration nationwide database, patients with type 2 diabetes mellitus who were newly initiated on a SGLT-2i or GLP-1RA between April 1, 2013 and September 1, 2020 were identified. The primary outcome was the incidence of any amputation, below-knee amputation (BKA), all clinical fractures, hip fracture, Fournier gangrene, acute pancreatitis, diabetic ketoacidosis (DKA), serious urinary tract infections (UTIs), and venous thromboembolism (VTE). All outcomes were compared between the treatment groups. Cox proportional hazard models were used to estimate adjusted hazard ratios (aHRs) for the comparative analysis. A total of 70,694 propensity-matched new users of SGLT-2i and GLP-1RA were identified. The use of SGLT-2 inhibitors, compared with GLP-1RA, was not associated with an increased rate of any amputation (aHR 1.02, 95% confidence interval [CI] 0.82 to 1.27), BKA (aHR 1.05, 95% CI 0.84 to 1.32), all clinical fractures (aHR 0.94, 95% CI 0.86 to 1.03), hip fractures (aHR 0.82, 95% CI 0.50 to 1.32), DKA (aHR 1.66, 95% CI 0.97 to 2.85), VTE (aHR 1.02, 95% CI 0.80 to 1.30), acute pancreatitis (aHR 1.02, 95% CI 0.80 to 1.30), and Fournier gangrene (aHR 0.92 95% CI 0.61 to 1.38). Lower rates of serious UTIs were observed in the SGLT-2i group than in the GLP-1RA group (aHR 0.74, 95% CI 0.64 to 0.84). This real-world study found that SGLT-2i use compared with GLP-1RA did not increase the rate of amputation, BKA, clinical fractures, hip fracture, Fournier gangrene, acute pancreatitis, DKA, serious UTIs, and VTE in veteran patients.

CHAnges in Diuretic Medication Prescribing and Surrogate Laboratory Parameters After Initiating EmpagliflOziN in Veterans (CHAMPION Cohort Study).

BACKGROUND AND OBJECTIVES: Sodium-glucose cotransporter type 2 inhibitors have evolved into a novel drug class utilized for reductions in cardiovascular risk and heart failure hospitalization. We aimed to describe the impact of sodium-glucose cotransporter type 2 inhibitors on diuretic prescribing patterns and intermediate laboratory outcomes in patients with and without diuretic use. METHODS: This retrospective cohort study included patients taking empagliflozin as of 1 July, 2021. Patients were assigned to the intervention group if prescribed a diuretic concomitantly or a control group otherwise. The primary outcome was the impact of empagliflozin on diuretic prescribing (i.e., no change, discontinuation, decrease, increase). Secondary outcomes were change in weight, hemoglobin A1c, estimated glomerular filtration rate, hemoglobin, hematocrit, blood pressure, and electrolytes at 90 and 180 days. Mean differences were compared using the t-test between groups or the paired t-test within groups. Patients without diuretic use were matched 1:1 to patients taking diuretics using propensity scores. RESULTS: This study included 1189 patients: 750 in the control group and 439 in the intervention group. After propensity score matching, baseline characteristics were well balanced. Of the 439 patients in the intervention group, 118 had changes in the diuretic regimen. There were 131 changes: 109 (83.2%) discontinuations, 13 (9.92%) decreases, and nine (6.87%) increases. The mean furosemide equivalent loop dose was reduced after empagliflozin initiation (50.62 mg vs 43.13 mg; p < 0.001). Among all patients, there was a decrease in weight (p = 0.01), estimated glomerular filtration rate (p < 0.001), and hemoglobin A1c (p < 0.001). There was an increase in hemoglobin (p < 0.001), hematocrit (p < 0.001), and magnesium (p < 0.001). In the propensity score-matched cohort, there was a significant reduction from baseline in mean weight in the intervention group compared with the control group (p < 0.001). CONCLUSIONS: This hypothesis-generating study suggests that sodium-glucose cotransporter type 2 inhibitors may lower diuretic requirements, further supported by a reduction in weight in the intervention cohort.

Impact of Pharmacist-Led Heart Failure Clinic on Optimization of Guideline-Directed Medical Therapy (PHARM-HF).

This prospective study included patients with heart failure (HF) with reduced ejection fraction (HFrEF) with LVEF < = 40% to evaluate the impact of pharmacist on guideline directed medical therapy (GDMT). The primary outcome was to compare proportion of triple GDMT achieved for Angiotensin-Converting-Enzyme-Inhibitors (ACEI)/Angiotensin-Receptor-Blockers (ARB)/Angiotensin-Receptor-Neprilysin-Inhibitors (ARNI), beta-blockers, aldosterone antagonists (AA), and quadruple GDMT which in additional to triple therapy, included Sodium glucose co-transporter 2 inhibitor (SGLT2i) at 90-day post-enrollment compared to baseline. Secondary endpoints included achieving target and/or maximally tolerated ACEI/ARB/ARNI and beta-blockers combined and individually as well as SGLT2i and AA GDMT at 90-day post-enrollment compared to baseline. We also compared combined and individual HF-related hospitalization/emergency room (ER) visits 90 days pre-/post-enrollment. Of the total 974 patients screened, 80 patients seen at least once in the heart failure medication titration clinic (HMTC) were included in the analysis. Median (IQR) age was 71 (57-69) years with majority white male. There was a significant improvement in the proportion of patients who achieved quadruple GDMT (p = 0.001) and triple GDMT (p-value = 0.020) at 90-day post-enrollment compared to baseline. The secondary GDMT outcomes were also significantly increased at 90 days post-enrollment compared to baseline. Significant difference in mean as well as proportion of combined HF-related hospitalization/ER-visits was found 90 days pre-/post-enrollment (p = 0.047). Our study found that pharmacist's intervention increased the proportion of patients who achieved GDMT at 90 days.