BEYOND METFORMIN: A DECADAL REVIEW OF EMERGING ORAL HYPOGLYCAEMICS AND THEIR REAL-WORLD IMPACT ON GLYCEMIC CONTROL

Background: The landscape of oral hypoglycemic agents (OHAs) for type 2 diabetes mellitus (T2DM) has transformed dramatically over the past two decades. Beyond metformin, newer classes—notably sodium-glucose cotransporter-2 (SGLT2) inhibitors, dipeptidyl peptidase-4 (DPP-4) inhibitors, and more recently oral glucagon-like peptide-1 receptor agonists (GLP-1 RAs)—offer distinct advantages but also unique risks. Objective: This review synthesises evidence from the last 20 years to evaluate the impact of trending OHAs on glycaemic control, body weight, cardiovascular outcomes, and adverse events, with a focus on real-world applicability. Methods: A structured PubMed search (2004–2024) was conducted for randomised controlled trials, meta-analyses, and retrospective observational studies. Inclusion criteria: adult T2DM patients, use of SGLT2 inhibitors, DPP-4 inhibitors, or oral GLP-1 RAs, with outcomes including HbA1c, major adverse cardiovascular events (MACE), or hospitalisation for heart failure. Exclusion criteria: animal studies, paediatric populations, and non-English articles. Results: Forty-three articles met inclusion criteria. SGLT2 inhibitors consistently reduced MACE (HR 0.86, 95% CI 0.80–0.92) and heart failure hospitalisations. DPP-4 inhibitors showed neutral cardiovascular effects but favourable safety. Oral semaglutide achieved HbA1c reductions of -1.2% to -1.6% with weight loss of 3–5 kg, albeit higher gastrointestinal side effects. Conclusion: Newer OHAs have moved beyond glucose lowering to target organ protection. Individualisation based on cardiovascular, renal, and weight profiles is now mandatory. Clinicians must navigate trade-offs between efficacy and tolerability.