GLP1 Receptor Agonists and SGLT2 Inhibitors for the Prevention or Delay of Type 2 Diabetes Mellitus Onset: A systematic review and meta-analysis

Farah Ghobar¹Ali Tarhini¹Zeinab Osman¹Sergio Sbeih¹Ralph Abou Ghayda¹Patena Matar¹Gaelle Haddad¹Amjad Kanaan¹Assaad Antoine Eid²Sami Azar¹Hilda E. Ghadieh^1*Frederic Harb^1*

• ¹Faculty of Medicine and Medical Sciences, University of Balamand, El-Koura, Lebanon
• ²Department of Anatomy, Cell Biology, and PPhysiological Sciences, Faculty of Medicine, American University of Beirut, Beirut, Lebanon

SGLT-2 inhibitors (SGLT-2i) and GLP-1 receptor agonists (GLP-1 RA) are widely used in diabetes care for their glycaemic benefits and additional effects on weight and cardiovascular risk. We conducted a meta-analysis to evaluate whether initiating these agents in individuals with prediabetes improves intermediate metabolic outcomes and may delay progression to type 2 diabetes mellitus (T2DM). We systematically searched PubMed, Embase, and Cochrane for randomized controlled trials (RCTs) assessing SGLT-2i, GLP-1 RA, or both in prediabetic or non-diabetic adults. Data extraction focused on glycaemic and weight outcomes; statistical analyses were performed in IBM SPSS and reported with 95% confidence intervals (CI). Fourteen RCTs met inclusion criteria, thirteen of which were double-blind, with baseline characteristics generally balanced between treatment and control groups. Both drug classes, when given individually, were associated with reductions in body weight relative to control, and fasting plasma glucose tended to be lower in treated participants (standardized mean difference [SMD] −5.40; 95% CI −10.70 to 2.24), although statistical significance was not consistently reached across all endpoints. HbA1c was reported in seven studies and showed a pooled effect trending toward reduction (SMD −6.95; 95% CI −14.24 to 2.98; p = 0.06), indicating a possible benefit that did not meet conventional thresholds for significance. Three studies evaluated incident diabetes with SGLT-2i and suggested fewer conversions to T2DM versus control, but this finding was not statistically significant (p = 0.08; SMD −2.21; 95% CI −5.11 to 0.69). Fasting insulin showed no clear change (SMD −1.74; 95% CI −6.84 to 3.37; p = 0.55). One small study reported a large effect with combination therapy; however, given the limited evidence base, this should be considered preliminary and hypothesis-generating. Overall, the synthesis supports that early pharmacological intervention with SGLT-2i or GLP-1 RA in prediabetes can improve weight and selected glycaemic measures and may help delay progression toward T2DM, though certainty is tempered by limited trials directly assessing incident diabetes and variability across populations and protocols. Additional, adequately powered RCTs—including head-to-head and combination-therapy studies with standardized outcomes—are warranted to define comparative effectiveness and clarify the potential for risk reduction in diabetes onset.