Insulin degludec/liraglutide ranks highest for HbA1c reduction with SUCRA value of 89.4%

This systematic review utilized a network meta-analysis design to evaluate multiple pharmacological options for patients with type 2 diabetes. The analysis included data from 12,815 patients and compared three fixed-ratio combination products against their individual components. The specific interventions included insulin degludec/liraglutide, insulin glargine/lixisenatide, and insulin degludec/insulin aspart. These were compared against monotherapies consisting of insulin degludec, insulin glargine, liraglutide, and lixisenatide. The primary outcomes assessed included reducing HbA1c, fasting plasma glucose, and the incidence of hypoglycemic events. Secondary outcomes focused on the incidence of treatment-emergent adverse events (TEAEs).

The analysis identified that insulin degludec/liraglutide had the highest probability of being optimal for reducing HbA1c with a SUCRA value of 89.4%. This same combination also showed the highest probability of being optimal for reducing fasting plasma glucose with a SUCRA value of 81.8%. Furthermore, insulin degludec/liraglutide demonstrated the highest probability of being optimal regarding the reduction of hypoglycemic event incidence with a SUCRA value of 57.6%. These findings suggest a favorable efficacy profile for this specific combination product within the evaluated network.

Regarding safety and tolerability, the study found that insulin degludec/liraglutide and insulin glargine/lixisenatide had a higher incidence of treatment-emergent adverse events (TEAEs) than insulin degludec/insulin aspart. The odds ratio for insulin degludec/liraglutide was 1.69 with a 95% CI of 1.08-2.65. The odds ratio for insulin glargine/lixisenatide was 1.67 with a 95% CI of 1.17-2.37. In contrast, insulin degludec/insulin aspart ranked highest regarding the incidence of TEAEs with a SUCRA value of 97.9%. Serious adverse events, discontinuations, and specific tolerability metrics were not reported in the source data.

Methodological limitations warrant cautious interpretation of these results. Inconsistency in the hypoglycemia network, likely due to varied definitions, warrants cautious interpretation. The SUCRA values indicate probabilistic ranking rather than direct statistical superiority. These probabilistic rankings must be understood as relative positions within the network rather than absolute measures of clinical performance. The lack of reported data on serious adverse events and discontinuations limits the ability to fully assess the safety profile in real-world practice.

These results provide a comparative framework for selecting basal insulin and GLP-1 receptor agonist combinations in type 2 diabetes management. Clinicians may consider insulin degludec/liraglutide when maximizing glycemic control and minimizing hypoglycemia are primary goals. However, the higher incidence of TEAEs for insulin degludec/liraglutide and insulin glargine/lixisenatide compared to insulin degludec/insulin aspart must be weighed against efficacy benefits. The absence of reported data on serious adverse events and discontinuations suggests that long-term safety profiles remain incompletely characterized in this analysis.

Several questions remain unanswered regarding the long-term durability of these glycemic effects and the specific mechanisms driving the difference in adverse event rates. The varied definitions of hypoglycemia across the included studies introduce uncertainty into the hypoglycemia network. Future research should aim to standardize outcome definitions and report comprehensive safety data including serious adverse events and discontinuation rates. Until such data are available, clinicians should rely on these probabilistic rankings while maintaining vigilance for adverse events in patients receiving insulin degludec/liraglutide or insulin glargine/lixisenatide.