Using Secondary Data to Evaluate Sex-based Heterogeneity of GLP-1 Agonists and SGLT2 Inhibitors on Cardiovascular-Kidney-Metabolic Health (CKMH) Outcomes in Real-world Settings (DASH-CKMH)

What this study is testing ClinicalTrials.gov NCT07188545 ↗

Description as written by the study sponsor.

Complex pathophysiological interactions among obesity, metabolic risk factors, chronic kidney disease (CKD), and the cardiovascular system lead to poor cardiovascular-kidney-metabolic health (CKMH), which is a major determinant of premature morbidity and mortality. Poor CKMH may lead to cardiovascular-kidney-metabolic syndrome (CKMS) - the five-stage framework introduced by The American Heart Association (AHA) which accounts for the critical overlap between cardiorenal syndrome and cardiometabolic disease. Evidence from randomized controlled trials shows glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose co-transporter-2 inhibitors (SGLT2is) may improve CKMH in individuals with Type 2 Diabetes (T2D) and/ or obesity. However, there is modest evidence suggesting differential effectiveness of GLP-1RA and SGLT2i drugs between males and females. The extent of these sex-based differences is currently unknown. In part, this may be due to underrepresentation of females in clinical trials. Exploring sex-based differences in GLP-1RA and SGLT2i treatment on CKMH outcomes is important to inform CKMS treatment and equity in CKMH. Robust secondary data sources present the opportunity to elucidate sex heterogeneity in GLP-1RA and SGLT2i treatment on CKMH outcomes. Using a target-trial emulation design, this study aims to observe differences in long-term CKMH outcomes between patients treated by GLP-1RA and SGLT2i medications versus those treated with active comparator medications, and whether there is an observed interaction between sex and treatment.

Treatments tested

• Intervention Drug

  GLP-1RA and/or SGLT2i adult users with ≥1 prescription for the intervention GLP-1RA or SGLT2i medications (including combination drugs or mixed therapies with comparator medications). GLP-1RAs include: Exenatide, Liraglutide, Semaglutide, Dulaglutide, Lixisenatide, Albiglutide, Tirzepatide. SGLT2is include: Canagliflozin, Dapagliflozin, Bexagliflozin, Empagliflozin, Ertugliflozin, Sotagliflozin.

• Active Comparator Drug

  DPP4i or Oral Obesity Agent adult users with ≥1 prescription for the comparator DPP4i or Oral Obesity Agent medications AND no intervention GLP-1RA or SGLT2i prescriptions in first 30 days of follow up. DPP4is include: Alogliptin, Saxagliptin, Linagliptin, Sitagliptin. Oral Obesity Agents include: Orlistat, Naltrexone-bupropion, Phentermine-topiramate, Phentermine, Diethylpropion, Bupropion (off-label), Topiramate (off-label)