Original Research

Impact of Liraglutide to Semaglutide Conversion on Glycemic Control and Cost Savings at a Veterans Affairs Medical Center

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Background: Semaglutide and liraglutide are glucagon-like peptide 1 receptor agonists (GLP-1 RAs) approved by the US Food and Drug Administration for patients with type II diabetes mellitus (T2DM). Patients with T2DM treated with liraglutide at the Michael E. DeBakey Veterans Affairs Medical Center (MEDVAMC) were converted to semaglutide. The primary objective was to assess changes in glycemic control and cost savings that resulted from this conversion.

Methods: We conducted a retrospective chart review of veterans without retinopathy treated at MEDVAMC between March 1, 2021, and November 30, 2021, who were converted from liraglutide 0.6 mg and 1.2 mg daily to semaglutide 0.25 mg weekly (titrated to 0.5 mg weekly after 4 weeks). To assess glycemic control, we compared hemoglobin A1c (HbA1c) values 3 to 12 months following conversion with baseline values. Cost savings were evaluated using outpatient pharmacy data.

Results: During the study, 411 patients were converted from liraglutide to semaglutide; 49 additional patients met the criteria for clinician education, and 14 were converted as a result. In total, 304 patients met the criteria for inclusion. At baseline, patients’ levels included: mean (SD) HbA1c, 8.1% (1.5); blood glucose, 187 (44.2) mg/dL; and body weight, 112.9 (23) kg. Three to 12 months postconversion, patients’ mean (SD) HbA1c significantly decreased to 7.6% (1.4) (P < .001), blood glucose decreased to 172.6 (39) mg/dL (P < .001), and body weight decreased to 105.2 (32.3) kg (P < .001). Cost savings exceeding $400,000 resulted from the conversion from liraglutide to semaglutide.

Conclusions: Conversion of liraglutide to semaglutide led to significant HbA1c decrease and weight loss and resulted in minimal changes to patients’ antihyperglycemic regimen. Common adverse effects included hypoglycemia and gastrointestinal intolerance. Due to the low conversion rate of liraglutide to semaglutide following education, a more effective method of education for clinicians to promote teleretinal imaging before conversion is warranted. Lastly, although the semaglutide cost savings initiative at MEDVAMC resulted in significant savings for the institution, a full cost-effective analysis is needed for further conclusion.



Semaglutide and liraglutide are glucagon-like peptide 1 receptor agonists (GLP-1 RAs) that are approved by the US Food and Drug Administration as subcutaneous injections for patients with type 2 diabetes mellitus (T2DM). Both are recommended by the American Diabetes Association (ADA) as first-line options for patients with concomitant atherosclerotic cardiovascular (CV) disease and exert therapeutic effect via incretin-like mechanisms.1 These agents lower blood glucose levels by stimulating insulin release, increasing the body’s sensitivity to insulin, and inhibiting inappropriate glucagon secretion.2,3 They also slow gastric emptying, resulting in decreased appetite and potential weight loss.4

The SUSTAIN (1-7) trials concluded that semaglutide presented an equivalent safety profile and greater efficacy compared with other GLP-1 RAs, including exenatide and dulaglutide.2 The SUSTAIN-10 open-label, head-to-head trial evaluating 1 mg semaglutide once weekly vs 1.2 mg liraglutide daily concluded that semaglutide was superior in hemoglobin A1c (HbA1c) and body weight reduction compared with liraglutide, with slightly increased gastrointestinal (GI) adverse effects (AEs).5 Similar to the LEADER trial assessing liraglutide, SUSTAIN-6 evaluated semaglutide in patients at increased CV risk and found that compared with placebo, semaglutide decreased rates of serious CV events, such as CV death, myocardial infarction, and stroke and were similar to the CV outcomes in the LEADER trial.2,6 Although initial results of the SUSTAIN-6 trial were thought to be nearly equivalent to the LEADER trial, analyses later published comparing both trials noted that semaglutide had more potent HbA1c lowering and weight loss benefit when compared with liraglutide.2,6 The cardioprotective outcomes of SUSTAIN-6 qualified semaglutide for inclusion in the current ADA Standards of Medical Care recommendations for CV risk reduction.6,7 However, despite the CV safety profile and efficacy associated with semaglutide, the SUSTAIN-6 trial noted an increased risk of diabetic retinopathy (DR) complications in 50 of 1648 patients (3%) treated with semaglutide compared with 29 of 1649 (1.8%) who received placebo (P = .02; hazard ratio, 1.76; 95% CI, 1.11-2.78).6 Of the 79 total patients who experienced retinopathy complications, 66 had retinopathy at baseline (42 of 50 [84%]) in the semaglutide group; 24 of 29 [83%] in the placebo group).6 Worsening of DR became one of the most notable AEs of semaglutide evaluated in clinical trials. This further deemed the effect as a warning in the semaglutide package insert to assist clinicians with treatment decisions.

As part of a US Department of Veterans Affairs (VA) National Lost Opportunity Cost Savings Initiative, which encompasses administrative efforts to promote more cost-effective yet safe and efficacious therapy options for veterans, the Michael E. DeBakey VA Medical Center (MEDVAMC) in Houston, Texas, converted a portion of patients with T2DM established on liraglutide to semaglutide. The 30-day supply cost of the 2-pack liraglutide 6 mg/mL (3 mL) injection pens for the MEDVAMC was $197.64. The 30-day supply cost for the singular multidose semaglutide 0.5 mg/0.375 mL (1.5 mL) injection pen was $115.15. Cost savings for the MEDVAMC facility were initially estimated to reach $642,522.

The subset of patients converted had to have undergone teleretinal imaging and not have a diagnosis of nonproliferative DR (NPDR), proliferative DR (PDR), or PDR with or without diabetic macular edema. These recommendations excluding various forms of retinopathy were implemented per local institution guidance supporting clinical data from the SUSTAIN trials. Patients diagnosed with these conditions were continued on liraglutide due to an increased risk of DR complications associated with semaglutide.

In the fall of 2021, there was also a standing list of patients on liraglutide who were not converted due to a lack of teleretinal imaging. As a result, there was potential for a quality improvement (QI) intervention to target this patient population, which could result in further cost savings for MEDVAMC and improved glycemic control because of increased conversion from liraglutide to semaglutide. The purpose of this project was to perform a QI assessment on this subset of patients both initially converted from liraglutide to semaglutide, and those who were yet to be converted due to a lack of teleretinal imaging to determine the impact on glycemic control and cost savings.


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