glucagon-like-peptide-1 and Urinary-Tract-Infections

Sodium-glucose cotransporter-2 (SGLT2) inhibitor-induced glycosuria is hypothesized to increase the risk of urinary tract infections (UTIs). We assessed the risk of UTIs associated with SGLT2 inhibitor initiation in type 2 diabetes.. We conducted a population-based cohort study using primary care data from the United Kingdom's Clinical Practice Research Datalink (CPRD) and administrative health-care data from Alberta, Canada. From a base cohort of new metformin users, we constructed 5 comparative cohorts, wherein the exposure contrast was defined as new use of SGLT2 inhibitors or 1 of 5 active comparators: dipeptidylpeptidase-4 (DPP-4) inhibitors, sulfonylureas (SU), glucagon-like peptide-1 receptor agonists (GLP-1 RA), thiazolidinediones (TZD) and insulin. We defined a composite UTI outcome based on hospitalizations or physician visit records. For each comparative cohort, we used high-dimensional propensity score matching to adjust for confounding and Cox proportional hazards regression to estimate the hazard ratios (HRs) in each database. We meta-analyzed estimates using a random-effects model.. SGLT2 inhibitor use was not associated with a higher risk of UTI compared with DPP-4 inhibitors (pooled HR, 1.08; 95% confidence interval [CI], 0.89 to 1.30), SU (pooled HR, 1.08; 95% CI, 0.90 to 1.30), GLP-1 RA (pooled HR, 0.81; 95% CI, 0.61 to 1.09) or TZD (pooled HR, 0.81; 95% CI, 0.55 to 1.19). The risk of UTI was lower compared with insulin (pooled HR, 0.74; 95% CI, 0.63 to 0.87). The risk of UTI did not differ based on the SGLT2 inhibitor agent or dose. Last, SGLT2 inhibitor initiation was not associated with an increased risk of UTI recurrence.. SGLT2 inhibitor use is not associated with an increased risk of UTIs, compared with other antidiabetic agents.

Topics: Alberta; Cohort Studies; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Glucagon-Like Peptide 1; Glucose; Humans; Hypoglycemic Agents; Insulin; Propensity Score; Sodium; Sodium-Glucose Transporter 2 Inhibitors; Sulfonylurea Compounds; Thiazolidinediones; Urinary Tract Infections

Topics: Cohort Studies; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Glucagon-Like Peptide 1; Humans; Hypoglycemic Agents; Sodium-Glucose Transporter 2 Inhibitors; Urinary Tract Infections

Prior studies evaluating risk for severe urinary tract infections (UTIs) with sodium-glucose cotransporter-2 (SGLT-2) inhibitors have reported conflicting findings.. To assess whether patients initiating use of SGLT-2 inhibitors were at increased risk for severe UTI events compared with those initiating use of dipeptidyl peptidase-4 (DPP-4) inhibitors or glucagon-like peptide-1 receptor (GLP-1) agonists.. Population-based cohort study.. 2 large, U.S.-based databases of commercial claims (March 2013 to September 2015).. Within each database, 2 cohorts were created and matched 1:1 on propensity score. Patients were aged 18 years or older, had type 2 diabetes mellitus, and were initiating use of SGLT-2 inhibitors versus DPP-4 inhibitors (cohort 1) or GLP-1 agonists (cohort 2).. The primary outcome was a severe UTI event, defined as a hospitalization for primary UTI, sepsis with UTI, or pyelonephritis; the secondary outcome was outpatient UTI treated with antibiotics. Hazard ratios (HRs) were estimated in each propensity score-matched cohort, with adjustment for more than 90 baseline characteristics.. After 1:1 matching on propensity score, 123 752 patients were identified in cohort 1 and 111 978 in cohort 2 in the 2 databases. In cohort 1, persons newly receiving SGLT-2 inhibitors had 61 severe UTI events (incidence rate [IR] per 1000 person-years, 1.76), compared with 57 events in the DPP-4 inhibitor group (IR, 1.77) (HR, 0.98 [95% CI, 0.68 to 1.41]). In cohort 2, those receiving SGLT-2 inhibitors had 73 events (IR, 2.15), compared with 87 events in the GLP-1 agonist group (IR, 2.96) (HR, 0.72 [CI, 0.53 to 0.99]). Findings were robust across sensitivity analyses; within several subgroups of age, sex, and frailty; and for canagliflozin and dapagliflozin individually. In addition, SGLT-2 inhibitors were not associated with increased risk for outpatient UTIs (cohort 1: HR, 0.96 [CI, 0.89 to 1.04]; cohort 2: HR, 0.91 [CI, 0.84 to 0.99]).. Generalizability of the study findings may be limited to patients with commercial insurance.. In a large cohort of patients seen in routine clinical practice, risk for severe and nonsevere UTI events among those initiating SGLT-2 inhibitor therapy was similar to that among patients initiating treatment with other second-line antidiabetic medications.. Brigham and Women's Hospital, Division of Pharmacoepidemiology and Pharmacoeconomics.

Topics: Databases, Factual; Dipeptidyl-Peptidase IV Inhibitors; Female; Glucagon-Like Peptide 1; Humans; Hypoglycemic Agents; Incidence; Male; Middle Aged; Propensity Score; Risk Factors; Sodium-Glucose Transporter 2 Inhibitors; United States; Urinary Tract Infections