Glucagon-like Peptide-1 receptor agonists versus dipeptidyl-peptidase 4 inhibitors in advanced chronic kidney disease and end stage kidney disease: Real world effectiveness and persistence of therapy.

Atherosclerotic cardiovascular disease is the leading cause of death in people with type 2 diabetes (T2D) and chronic kidney disease (CKD) or end-stage kidney disease (ESKD). Glucagon-Like Peptide-1 receptor agonists (GLP-1RA) reduce cardiovascular events, improve glycemic control, promote weight loss, and slow progression of nephropathy. Despite these benefits and professional society treatment guidelines recommendations, GLP-1RAs remain under-utilized in people with advanced CKD and ESKD due to tolerability and safety concerns. We conducted a retrospective cohort study comparing clinical outcomes and medication use details after initiating GLP-1RA or dipeptidyl-peptidase 4 inhibitor (DPP-4i) in people with T2D and advanced CKD or ESKD. Eligible patients were identified via electronic health record query with extraction of baseline demographics, vital signs, and laboratory values. A manual chart review was undertaken to confirm eligibility, medication use, and extract a detailed account of all side effects. A total of 236 eligible patients (149 in the GLP-1RA group and 87 in the DPP-4i group) were identified. The average duration of treatment was 1036 (±909.9) and 1109 (±1090.9) days for GLP-1RA and DPP-4i, respectively. The average percentage weight loss from baseline to 36 months of treatment in the GLP-1RA group was -9.6 % (95 % CI, -11.3 to -7.8) versus -2.4 % (95 % CI, -5.4 to 0.5) in the DPP-4i group (estimated treatment difference (ETD) -7.1 (95 % CI, -10.6 to -3.7) percentage-points, p < 0.001). The change in HbA1c from baseline to 36 months of treatment was significantly greater in the GLP-1RA (-1.0 %) compared with the DPP-4i group (0.2 %) (ETD -1.2 (95 % CI, -2.1 to -0.3) percentage-points, p = 0.04). In patients with T2D and advanced CKD or ESKD, treatment with GLP-1RAs in a real-world setting had long treatment persistence, and compared to DPP-4is, was associated with greater weight loss and glycemic improvement.

Sidra FNU ，Agarwal S ，Lockhart Pastor P ，Xie D ，Li X ，Lingvay I ... -  《-》

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》

Durability of Effectiveness Between Users of Once-Weekly Semaglutide and Dipeptidyl Peptidase 4 Inhibitors (DPP-4i) in US Adults with Type 2 Diabetes.

Tan X ，Liang Y ，Gamble C ，King A ... -  《-》

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 ... -  《-》

A randomized phase 2b trial examined the effects of the glucagon-like peptide-1 and glucagon receptor agonist cotadutide on kidney outcomes in patients with diabetic kidney disease.

Cotadutide is a glucagon-like peptide-1 (GLP-1) and glucagon receptor agonist that may improve kidney function in patients with type 2 diabetes (T2D) and chronic kidney disease (CKD). In this phase 2b study, patients with T2D and CKD (estimated glomerular filtration rate [eGFR] of 20 or more and under 90 mL/min per 1.73 m2 and urinary albumin-to-creatinine ratio [UACR] over 50 mg/g) were randomized 1:1:1:1:1 to 26 weeks' treatment with standard of care plus subcutaneous cotadutide uptitrated to 100, 300, or 600 μg, or placebo daily (double-blind), or the GLP-1 agonist semaglutide 1 mg once weekly (open-label).The co-primary endpoints were absolute and percentage change versus placebo in UACR from baseline to the end of week 14. Among 248 randomized patients, mean age 67.1 years, 19% were female, mean eGFR was 55.3 mL/min per 1.73 m2, geometric mean was UACR 205.5 mg/g (coefficient of variation 270.0), and 46.8% were receiving concomitant sodium-glucose co-transporter 2 inhibitors. Cotadutide dose-dependently reduced UACR from baseline to the end of week 14, reaching significance at 300 μg (-43.9% [95% confidence interval -54.7 to -30.6]) and 600 μg (-49.9% [-59.3 to -38.4]) versus placebo; with effects sustained at week 26. Serious adverse events were balanced across arms. Safety and tolerability of cotadutide 600 μg were comparable to semaglutide. Thus, our study shows that in patients with T2D and CKD, cotadutide significantly reduced UACR on top of standard of care with an acceptable tolerability profile, suggesting kidney protective benefits that need confirmation in a larger study.

Selvarajah V ，Robertson D ，Hansen L ，Jermutus L ，Smith K ，Coggi A ，Sánchez J ，Chang YT ，Yu H ，Parkinson J ，Khan A ，Chung HS ，Hess S ，Dumas R ，Duck T ，Jolly S ，Elliott TG ，Baker J ，Lecube A ，Derwahl KM ，Scott R ，Morales C ，Peters C ，Goldenberg R ，Parker VER ，Heerspink HJL ，study investigators ... -  《-》