SGLT-2 inhibitors, GLP-1 receptor agonists, and DPP-4 inhibitors and risk of hyperkalemia among people with type 2 diabetes in clinical practice: population based cohort study.

To evaluate the comparative effectiveness of sodium-glucose cotransporter-2 (SGLT-2) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, and dipeptidyl peptidase-4 (DPP-4) inhibitors in preventing hyperkalemia in people with type 2 diabetes in routine clinical practice. Population based cohort study with active-comparator, new user design. Claims data from Medicare and two large commercial insurance databases in the United States from April 2013 to April 2022. 1:1 propensity score matched adults with type 2 diabetes newly starting SGLT-2 inhibitors versus DPP-4 inhibitors (n=778 908), GLP-1 receptor agonists versus DPP-4 inhibitors (n=729 820), and SGLT-2 inhibitors versus GLP-1 receptor agonists (n=873 460). Hyperkalemia diagnosis in the inpatient or outpatient setting. Secondary outcomes were hyperkalemia defined as serum potassium levels ≥5.5 mmol/L and hyperkalemia diagnosis in the inpatient or emergency department setting. Starting SGLT-2 inhibitor treatment was associated with a lower rate of hyperkalemia than DPP-4 inhibitor treatment (hazard ratio 0.75, 95% confidence interval (CI) 0.73 to 0.78) and a slight reduction in rate compared with GLP-1 receptor agonists (0.92, 0.89 to 0.95). Use of GLP-1 receptor agonists was associated with a lower rate of hyperkalemia than DPP-4 inhibitors (0.79, 0.77 to 0.82). The three year absolute risk was 2.4% (95% CI 2.1% to 2.7%) lower for SGLT-2 inhibitors than DPP-4 inhibitors (4.6% v 7.0%), 1.8% (1.4% to 2.1%) lower for GLP-1 receptor agonists than DPP-4 inhibitors (5.7% v 7.5%), and 1.2% (0.9% to 1.5%) lower for SGLT-2 inhibitors than GLP-1 receptor agonists (4.7% v 6.0%). Findings were consistent for the secondary outcomes and among subgroups defined by age, sex, race, medical conditions, other drug use, and hemoglobin A1c levels on the relative scale. Benefits for SGLT-2 inhibitors and GLP-1 receptor agonists on the absolute scale were largest for those with heart failure, chronic kidney disease, or those using mineralocorticoid receptor antagonists. Compared with DPP-4 inhibitors, the lower rate of hyperkalemia was consistently observed across individual agents in the SGLT-2 inhibitor (canagliflozin, dapagliflozin, empagliflozin) and GLP-1 receptor agonist (dulaglutide, exenatide, liraglutide, semaglutide) classes. In people with type 2 diabetes, SGLT-2 inhibitors and GLP-1 receptor agonists were associated with a lower risk of hyperkalemia than DPP-4 inhibitors in the overall population and across relevant subgroups. The consistency of associations among individual agents in the SGLT-2 inhibitor and GLP-1 receptor agonist classes suggests a class effect. These ancillary benefits of SGLT-2 inhibitors and GLP-1 receptor agonists further support their use in people with type 2 diabetes, especially in those at risk of hyperkalemia.

Fu EL ，Wexler DJ ，Cromer SJ ，Bykov K ，Paik JM ，Patorno E ... -  《BMJ-British Medical Journal》

Glucagon-like peptide-1 receptor agonists before upper gastrointestinal endoscopy and risk of pulmonary aspiration or discontinuation of procedure: cohort study.

To assess whether use of glucagon-like peptide-1 (GLP-1) receptor agonists before upper gastrointestinal endoscopy is associated with increased risk of pulmonary aspiration or discontinuation of the procedure compared with sodium-glucose cotransporter-2 (SGLT-2) inhibitors. Cohort study. Two deidentified US commercial healthcare databases. 43 365 adults (≥18 years) with type 2 diabetes who used a GLP-1 receptor agonist or SGLT-2 inhibitor within 30 days before upper gastrointestinal endoscopy. The primary outcome was pulmonary aspiration on the day of or the day after endoscopy, defined using diagnostic codes. The secondary outcome was discontinuation of endoscopy. Risk ratios and corresponding 95% confidence intervals (CIs) were estimated after fine stratification weighting based on propensity score. After weighting, 24 817 adults used a GLP-1 receptor agonist (mean age 59.9 years; 63.6% female) and 18 537 used an SGLT-2 inhibitor (59.8 years; 63.7% female). Among users of GLP-1 receptor agonists and SGLT-2 inhibitors, the weighted risk per 1000 people was, respectively, 4.15 and 4.26 for pulmonary aspiration and 9.79 and 4.91 for discontinuation of endoscopy. Compared with SGLT-2 inhibitor use, GLP-1 receptor agonist use was not associated with an increased risk of pulmonary aspiration (pooled risk ratio 0.98, 95% CI 0.73 to 1.31), although it was associated with a higher risk for discontinuation of endoscopy (1.99, 1.56 to 2.53). In this comparative cohort study, no increased risk of pulmonary aspiration during upper gastrointestinal endoscopy was observed among adults with type 2 diabetes using GLP-1 receptor agonists compared with SGLT-2 inhibitors within 30 days of the procedure; however, GLP-1 receptor agonists were associated with a higher risk of discontinuation of endoscopy, possibly owing to a higher risk of retained gastric content. In the absence of evidence from randomized trials, these findings could inform future practice recommendations on the preprocedural protocol for patients requiring endoscopy.

Alkabbani W ，Suissa K ，Gu KD ，Cromer SJ ，Paik JM ，Bykov K ，Hobai I ，Thompson CC ，Wexler DJ ，Patorno E ... -  《BMJ-British Medical Journal》

Newer Pharmacologic Treatments in Adults With Type 2 Diabetes: A Clinical Guideline From the American College of Physicians.

Qaseem A ，Obley AJ ，Shamliyan T ，Hicks LA ，Harrod CS ，Crandall CJ ，Clinical Guidelines Committee of the American College of Physicians ，Balk EM ，Cooney TG ，Cross JT Jr ，Fitterman N ，Lin JS ，Maroto M ，Miller MC ，Shekelle P ，Tice JA ，Tufte JE ，Etxeandia-Ikobaltzeta I ，Yost J ... -  《-》

Cardiovascular, Kidney, and Safety Outcomes With GLP-1 Receptor Agonists Alone and in Combination With SGLT2 Inhibitors in Type 2 Diabetes: A Systematic Review and Meta-Analysis.

Neuen BL ，Fletcher RA ，Heath L ，Perkovic A ，Vaduganathan M ，Badve SV ，Tuttle KR ，Pratley R ，Gerstein HC ，Perkovic V ，Heerspink HJL ... -  《-》

Rationale for the Early Use of Sodium-Glucose Cotransporter-2 Inhibitors in Patients with Type 2 Diabetes.

Handelsman Y 《-》