What is the 'real-world' experience with fixed-ratio combination therapy (insulin + GLP-1 receptor agonist) in routine clinical practice? Take-home messages for clinicians regarding key outcomes.

AIMS: The fixed-ratio combinations (FRCs) of a basal insulin and glucagon-like peptide-1 receptor agonist (GLP-1 RA), IDegLira (insulin degludec/liraglutide) and iGlarLixi (insulin glargine/lixisenatide), offer a once-daily injectable treatment option for adults with type 2 diabetes (T2D), combining complementary mechanisms of action to target both fasting and postprandial hyperglycaemia. While randomized controlled trials have demonstrated their efficacy and safety, real-world evidence (RWE) provides important insights into their effectiveness, tolerability and use across routine clinical practice. MATERIALS AND METHODS: This is a narrative review of selected real-world studies assessing the FRCs IDegLira and iGlarLixi in adults with T2D. Studies assessing the use of FRCs to intensify and simplify therapy, as well as their use in special populations such as older adults were reviewed and are summarized. RESULTS: Among individuals inadequately controlled on oral antihyperglycaemic drugs (OADs), basal insulin ± OADs, or GLP-1 RAs, initiation of FRC therapy consistently improved glycaemic outcomes, supported modest weight loss or stability, and was associated with a low risk of hypoglycaemia. FRCs have also been evaluated as a strategy for simplifying complex insulin regimens. Transitions from basal-bolus or premixed insulin to FRCs maintained or improved glycaemic control while reducing total daily insulin dose and injection burden. Evidence in special populations and clinical contexts further supports the utility of FRCs. In older adults, FRC use was associated with reductions in HbA1c and hypoglycaemia risk, along with improvements in treatment satisfaction and functional measures. During Ramadan fasting, iGlarLixi demonstrated favourable glycaemic control, low hypoglycaemia incidence, modest weight loss and high adherence. Studies assessing glycaemic control using continuous glucose monitoring showed improvements in time in range, reductions in time above range and stable time below range, indicating enhanced glycaemic stability without increased risk of hypoglycaemia. Two real-world head-to-head studies comparing IDegLira and iGlarLixi found both FRCs to be effective and well tolerated. IDegLira was associated with greater weight loss and lower insulin dose requirements, while iGlarLixi showed advantages in postprandial glucose control. Both agents demonstrated significant improvements in HbA1c and low rates of hypoglycaemia. CONCLUSIONS: Collectively, these real-world studies confirm that FRCs are effective, safe and patient-centred treatment options for adults with T2D. Their simplified dosing, metabolic benefits and favourable safety profiles support their use for both therapy intensification and de-intensification across a broad spectrum of clinical scenarios. These findings reinforce results from randomized controlled trials, providing further confidence in the role of FRCs in contemporary diabetes care.