Weight Loss with Empagliflozin versus Liraglutide

Weight Loss with Empagliflozin versus Liraglutide
Sarah Clark, Pharm.D., Fairview Pharmacy Services

Background: Newer agents for Type 2 Diabetes Mellitus (T2DM), glucagon-like peptide-1 agonists  (GLP-1 RAs) and sodium glucose cotransporter 2 (SGLT2) inhibitors, are being prescribed with increasing frequency thanks to their beneficial cardiovascular outcomes, ability to cause weight loss, and support for their use in the American Diabetes Association (ADA) and American Association of Clinical Endocrinologists (AACE) guidelines. Weight loss is known to improve glycemic control and reduce cardiovascular risk and is often in line with the patient’s personal health goals. Both the SGLT2 inhibitor empagliflozin and the GLP-1 RA liraglutide were shown to cause weight loss in clinical trials, but there are no head-to-head trials comparing weight loss outcomes for these agents.

Objective: To assess the differences in weight loss outcomes of empagliflozin and liraglutide in overweight or obese veterans with T2DM.

Study Design: This study was a multi-site, observational, cohort study including veterans with T2DM who had a hemoglobin A1c ≥7%, a body mass index (BMI) ≥27 kg/m2, and who were not prescribed insulin at baseline.This cohort was prescribed either liraglutide or empagliflozin and followed for one year; the primary outcome assessed was change in weight using multiple regression. The secondary outcomes assessed were the change in A1c and the proportion of study subjects reaching ≥5% weight loss.

Results: The final cohort consisted of 298 patients treated with liraglutide and 247 patients treated with empagliflozin. The average weight loss in both groups was two to three kilograms over one year.  Weight loss was not significantly different between liraglutide (−2.17 kg [95% CI −2.91 to −1.42]) and empagliflozin (−2.81 kg [95% CI −3.43 to −2.20]) groups. These results were adjusted for covariates, such as BMI, age, insulin exposure, and medication adherence, and the difference between the agents remained insignificant. For secondary outcomes, there was no difference found in A1c change from baseline, with liraglutide lowering A1c by 0.83% [95% CI −1.05% to −0.62%] and empagliflozin lowering A1c by 0.71% [95% CI −0.89% to −0.53%; P>0.05]. Finally, the proportion of patients with ≥5% weight loss was not statistically significant between liraglutide (6.4%) and empagliflozin (4.5%) groups (P>0.05).

Limitations: The study population was primarily older white males with average renal function, making these findings less applicable to the general population. A second limitation is that some study subjects required treatment with insulin during the study period, which is known to cause weight gain. Other limitations include considerable differences in baseline characteristics between study arms, a relatively small sample size, and the participation of some study subjects in weight management programs. 

Conclusions: This study did not show a significant difference in weight loss outcomes between empagliflozin and liraglutide at one year. There was no significant difference in A1c lowering or proportion of subjects with ≥5% weight loss. Both medications caused modest weight loss and improvement in the A1c. When selecting between these agents, the decision should be based on patient preference, route of administration, cost, and comorbidities.

Key Point: Despite popular belief that GLP-1 RAs lead to more weight loss than SGLT2 inhibitors, empagliflozin and liraglutide had no significant difference in weight outcomes at one year.


  1. Grabarczyk TR, Wissman NK. Weight Outcomes With Empagliflozin as Compared With Liraglutide in Veterans With Type 2 Diabetes Mellitus. Ann Pharmacother. 2020;doi:10.1177/1060028020915791