Advantages of Liraglutide for Type 2 Diabetes Management After Hospital Discharge

Liraglutide initiation after hospital discharge was comparable to insulin for glycemic control, with less incidence of hypoglycemia. 

When transitioning a patient from a hospital setting to an outpatient setting, one primary goal is to prevent hospital readmissions. For patients with diabetes, poor glycemic control due to poor optimization of therapy can lead to rehospitalization. There are various changes to a patient’s diabetes medication regimen one can make to meet this goal. Based on a study by Wu et al., one recommendation by the 2021 ADA Standards of Care guideline mentions initiating insulin therapy for patients with an admission A1c of ≥9% to reduce readmission rates. One concern for initiating insulin is hypoglycemia, especially for insulin-naïve patients. GLP-1 agonists are alternative agents that may provide similar effects on glycemic control with a lower risk of hypoglycemia, as demonstrated by the EAGLE trial amongst patients in an ambulatory care setting. 

A recent non-inferiority randomized control trial looked to see if safety and efficacy trends for GLP-1 agonists could apply to patients post hospital discharge. Investigators enrolled admitted patients with T2DM from general medicine/surgical floors. At discharge, treatment-naïve patients either received liraglutide or insulin glargine monotherapy. Patients who took oral medications for diabetes before hospital admission continued their regimen at discharge in addition to liraglutide or insulin glargine. If their baseline A1c was >8%, then the treatment-naïve patients also received metformin. Initial insulin doses depended on the patient’s baseline A1c and hospital glargine dose. Every two weeks, investigators would follow up with patients via telephone to measure outcomes and titrate doses. Periodic in-person follow-up appointments were scheduled as well. The primary endpoint was the change in A1c levels 12- and 26- weeks post-discharge. Secondary outcomes included changes in fasting and postprandial blood glucose and the incidence of hypoglycemia. They also looked at how many patients could achieve a goal A1c of <7% without experiencing weight gain and hypoglycemia. The authors used the Wilcoxon test to compare continuous outcomes and Chi-squared or Fischer’s exact test for categorical outcomes. 

The intention-to-treat analysis included 273 patients who received either liraglutide (n=136) or insulin glargine (n=137). Of note, loss to follow-up was high in this study (~40%), with greater patient attrition being observed in the liraglutide group (41.2%) than those taking insulin (32.2%) by week 26. Both the liraglutide group (baseline A1c 8.3% ± 0.9%) and the insulin group (8.4% ± 0.8%) saw reductions in mean A1c at week 12 (7.14% ± 1.3% and 7.4% ± 1.2%, respectively; p=0.04) and at week 26 (7.12% ± 1.3% and 7.68% ± 1.6%, respectively; p=0.016). At week 26, liraglutide led to significant reductions in body weight (-4.77 ± 8 kg) while insulin caused mild weight gain (+0.6 ± 11 kg) for a mean difference of 5.38 kg (95% CI 2.28-8.48; p <0.001). Furthermore, liraglutide had a lower incidence of hypoglycemia [18 events (13%) vs 31 events (23%); p = 0.038] but had comparable rates of clinically significant (<54 mg/dL) and severe hypoglycemia (<40 mg/dL). Also, more patients in the liraglutide group were able to achieve an A1c < 7% without experiencing hypoglycemia or weight gain by week 12 (41% vs. 24%; p = 0.02) and week 26 (39% vs. 22%; p = 0.014). Other secondary efficacy outcomes were nonsignificant by week 26. A key finding was that liraglutide led to higher rates of nausea and vomiting (p<0.01 for both). As a result, this led to more discontinuations secondary to adverse events (10% vs. 0%; p <0.001). Besides gastrointestinal (GI) adverse events, the incidence of other safety outcomes (including readmission) was comparable between the groups (p >0.05).  

In conclusion, liraglutide initiation is comparable to insulin for glycemic control in patients with uncontrolled T2DM after discharge. Additional benefits of using GLP-1 agonists over insulin include weight loss and a lower risk of hypoglycemia. However, this study also showed higher treatment discontinuation rates in patients who either did not take injectable medications before admission or were not treated for diabetes before admission. Furthermore, the GI-related side effects of GLP-1 agonists led to higher rates of discontinuation. These observations show the importance of counseling on new medications during the transition-of-care process to improve adherence and reduce overall complications. With adequate counseling, GLP-1 agonists can be a great alternative to insulin for patients who require additional glycemic control after hospital discharge. 

Practice Pearls

• Liraglutide is comparable to insulin for glycemic control post-hospital discharge and provides weight loss benefits and a lower risk of hypoglycemia. 
• A critical clinical pearl of GLP-1 agonists is GI-related side effects such as nausea and vomiting. 
• Discharge counseling is recommended to improve adherence and outcomes. 

Pasquel, Francisco J, et al. “Liraglutide hospital discharge trial: A randomized controlled trial comparing the safety and efficacy of liraglutide versus insulin glargine for the management of patients with type 2 diabetes after hospital discharge.” Diabetes, obesity & metabolism vol. 23,6 (2021): 1351-1360. doi:10.1111/dom.14347

Wu, Eric Q et al. “Outcomes associated with post-discharge insulin continuity in US patients with type 2 diabetes mellitus initiating insulin in the hospital.” Hospital practice (1995) vol. 40,4 (2012): 40-8. doi:10.3810/hp.2012.10.1002

American Diabetes Association. “15. Diabetes Care in the Hospital: Standards of Medical Care in Diabetes-2021.” Diabetes care vol. 44, Suppl 1 (2021): S211-S220. doi:10.2337/dc21-S015

D’Alessio, D et al. “Comparison of insulin glargine and liraglutide added to oral agents in patients with poorly controlled type 2 diabetes.” Diabetes, obesity & metabolism vol. 17,2 (2015): 170-8. doi:10.1111/dom.12406

Andy Dao, PharmD Candidate, University South Florida Taneja College of Pharmacy