INTRODUCTION: For people with type 2 diabetes (T2DM) inadequately controlled 
with oral antidiabetic drugs (OADs), evidence from both randomized controlled 
trials (RCTs) and real-world studies has demonstrated that treatment 
intensification with liraglutide offers effective glycemic control, weight 
reduction, and a lower risk of hypoglycemia compared to treatment 
intensification with insulin or additional OADs. Sodium glucose cotransporter 2 
(SGLT-2) inhibitors are a new class of OADs that have also been shown to be 
effective in T2DM patients inadequately controlled with OADs. Currently there 
are no head-to-head RCTs comparing these to liraglutide.
METHODS: We aimed to evaluate the relative efficacy, using network meta-analysis 
(NMA), of treatment intensification with liraglutide and SGLT-2 inhibitors 
people with T2DM who have been treated with metformin (alone or in combination 
with SU, DPP-4, and TZD). We performed a systematic literature review to 
identify relevant RCTs comparing liraglutide (1.2 and 1.8 mg), canagliflozin 
(100 and 300 mg), empagliflozin (10 and 25 mg), or dapagliflozin (5 and 10 mg) 
to placebo. To strengthen the indirect evidence base, we also included 
non-placebo RCTs where sitagliptin (100 mg) was the active comparator. Bayesian 
NMA was performed on the following outcomes to assess the relative efficacy and 
safety of interventions: reduction (change) in HbA1c, weight, and fasting plasma 
glucose (FPG) as well as proportion reaching target HbA1c (<7%), and risk of 
hypoglycemia. Doses for each intervention were considered separately.
RESULTS: A total of 16 RCTs were identified. All trials were similar with 
respect to important baseline characteristics and study design. Both doses of 
liraglutide were generally statistically significantly superior to the SGLT-2s 
with respect to change from baseline in HbA1c and FPG as well as odds of 
reaching target HbA1c <7%. For weight, canagliflozin 300 mg was superior to 
liraglutide 1.2 mg, and SGLT-2s were generally associated with larger change 
from baseline in weight. For risk of major or minor hypoglycemia, no differences 
were found between treatments.
CONCLUSIONS: Compared to SGLT-2 inhibitors, liraglutide offers improvement in 
HbA1c and FPG. Reductions in weight are likely comparable between liraglutide 
and SGLT-2s. Liraglutide did not differ from SGLT-2s in terms of risk of 
hypoglycemia. Given the lack of head-to-head evidence, this analysis provides 
valuable insight into the comparative outcomes of liraglutide versus SGLT-2 
inhibitors.