Related Experiment Video
Updated: Mar 6, 2026

Human Liver Microphysiological System for Assessing Drug-Induced Liver Toxicity In Vitro
Published on: January 31, 2022
Who is missing from SGLT-2 inhibitor trials? Implications for drug safety and generalizability: a systematic review
Mohammad Ali Omrani1, Bala Swetha Baskaran1, Hasti Sadeghi2
1Department of Physiology and Pharmacology, Western University, London, ON, Canada.
Introduction:
SGLT-2 inhibitors improve type 2 diabetes and heart failure outcomes, yet representation of key demographic and clinical subgroups remains unclear. We aimed to quantify their representation in phase 3/4 trials.
Methods:
We searched CENTRAL, MEDLINE, and Embase (inception-5 May 2025) for trials (≥300 participants) reporting subgroup enrollment. We estimated pooled prevalence using random-effects meta-analyses and calculated exploratory Participation-to-Prevalence Ratios (PPRs) against real-world U.S. disease burden.
Results:
Across 91 RCTs, type 2 diabetes prevalence was: females 43.8% (95% CI 42.0%-45.7%), eGFR < 60 32.5% (13.1%-55.6%), older adults 31.8% (25.7%-38.2%), and Black participants 4.9% (4.3%-5.6%). In heart failure, prevalence was: older adults 68.7% (59.9%-76.8%), females 34.1% (27.8%-40.7%), and Black participants 7.6% (5.7%-9.7%). Exploratory PPRs indicated underrepresentation of Black participants (0.3 diabetes; 0.5 heart failure), older adults in diabetes (0.7), and females in heart failure (0.7). Data for liver disease and children/adolescents were insufficient.
Conclusions:
Prevalence was low for Black participants in both populations, older adults in diabetes trials, and females in heart failure trials. These disparities, alongside the exclusion of children and adolescents, may limit safety data generalizability, underscoring the need for inclusive recruitment.
Protocol Registration:
www.crd.york.ac.uk/prospero identifier is CRD42024561154.
Related Concept Videos
Bioequivalence of Drugs: Drugs with Multiple Indications
Glucose Transporters
Facilitated diffusion-glucose transporters (GLUTs) are encoded by the solute-linked carrier (SLC) family 2, subfamily A gene family, or SLC2A. The 14 GLUT protein members are distributed into three classes:
Oral Hypoglycemic Agents: Biguanides and Glitazones
Dipeptidyl Peptidase 4 Inhibitors
Pharmacogenetics of Drug Transporters: P-Glycoprotein and Solute Carrier Transporters
Types of Biopharmaceutical Studies: Controlled and Non-Controlled Approaches
Non-controlled studies, commonly employed for initial exploration, lack a control group, rendering them susceptible to biases and external influences. In contrast,...