Effect of Liraglutide on Pneumococcal Vaccine Immunogenicity in Adults with Diabetes: A Randomized Controlled Trial

The primary objective is to determine whether initiation of a GLP-1 receptor agonist enhances the immunological response to pneumococcal vaccination in individuals with diabetes, addressing a potential strategy to improve vaccine efficacy in this high‑risk population. Secondary objectives include:

• Evaluating whether GLP‑1RA initiation attenuates the decline of the immunological response over time.
• Assessing whether long‑term GLP‑1RA therapy increases the immunological response to the pneumococcal vaccine.
• Investigating the effect of GLP‑1RA on serotype‑specific immunological responses.
• Comparing the immunological response in type 2 diabetes patients treated with GLP‑1RA to that of healthy controls.
• Characterising the vaccine adverse‑effects profile associated with GLP‑1RA use.
• Exploring broader effects of GLP‑1RA on immune system parameters.
• Analyzing real‑world data for associations between gut‑hormone therapies and reduced severity of infectious disease.

The trial enrolled adult participants of both sexes, comprising healthy volunteers and patients with type 2 diabetes mellitus. Age eligibility encompassed the adult age categories defined by the protocol (codes 3 and 4). Healthy controls were required to have a body mass index between 18 and 25 kg/m², absence of active chronic disease, and limited medication use. Patient cohorts included individuals with a diagnosis of type 2 diabetes mellitus who either were naïve to GLP‑1 receptor agonist therapy and had an indication to initiate treatment because of suboptimal HbA1c or high cardiovascular risk, or who had been receiving a stable dose of semaglutide for at least one year. Matching of patients to controls was based on BMI, glycaemic control, and cardiovascular risk profile. No specific dietary or physical‑activity restrictions were stipulated beyond the general health requirements. The sponsor did not provide information on the total number of participants.

The study is a controlled, multi‑arm investigation evaluating whether initiation of a GLP-1 receptor agonist enhances the immunological response to a pneumococcal vaccine in participants with type 2 diabetes mellitus (T2DM) compared with T2DM patients already receiving stable GLP‑1 therapy and healthy control subjects. Eligible individuals undergo a screening visit to confirm inclusion criteria, record baseline demographics, and obtain pre‑vaccination blood samples. At the baseline visit, participants receive a single intramuscular dose of Pneumovax 23 (0.5 ml) and, if assigned to the initiation arm, commence liraglutide (1.8 mg subcutaneously) according to standard dosing. Subsequent follow‑up visits are scheduled at one month and four months post‑vaccination for collection of serum to assess the primary endpoint, the fold‑increase in total pneumococcal IgG antibody levels, as well as secondary immunogenic and safety parameters. An end‑of‑study visit concludes the trial, incorporating final laboratory assessments and questionnaires on vaccine‑related adverse events. Participant involvement spans approximately four months from vaccination to the primary endpoint assessment, with additional time for screening. Early termination may occur if a participant experiences a serious adverse event related to the investigational product, withdraws consent, or fails to adhere to the protocol schedule.

The investigational product is liraglutide supplied as Victoza 6 mg/ml solution for injection in a pre‑filled pen. Each administered dose contains 1.8 mg of liraglutide and is delivered by subcutaneous injection. The medication is provided in a solution for injection format and is intended for daily administration throughout the treatment period.

The non‑experimental intervention is Pneumovax 23, a pneumococcal polysaccharide vaccine provided as a 0.5 ml solution for injection in a pre‑filled syringe. The vaccine is administered intramuscularly as a single dose and contains purified polysaccharide antigens from 23 pneumococcal serotypes.

Both study medications are administered under direct observation at scheduled study visits. Compliance with the daily subcutaneous liraglutide injections is monitored by patient diaries and verification of pen usage at each visit. The timing of the pneumococcal vaccine injection is recorded, and participants are observed for immediate post‑administration reactions. All dosing information is captured in the electronic case report form to ensure adherence to the protocol.

Efficacy will be evaluated using immunological and clinical parameters. The primary efficacy parameter is the fold‑increase in total pneumococcal IgG antibody levels measured four months after vaccination. Secondary efficacy parameters include the fold‑increase in total IgG antibody levels at one month post‑vaccination, serotype‑specific antibody level changes, plasma inflammation marker concentrations, immune cell counts, leukocyte ex vivo functional assays, responses to a vaccine‑related solicited adverse‑event questionnaire, and the incidence of hospitalization, intensive‑care admission, or death attributable to infectious disease.

Antibody concentrations will be quantified at the one‑month and four‑month visits following pneumococcal vaccination. Serotype‑specific antibody responses will be assessed at the same post‑vaccination timepoints. Laboratory analyses will be performed to determine plasma inflammation markers, enumerate immune cell subsets, and evaluate leukocyte function ex vivo. The adverse‑event questionnaire will be administered during scheduled follow‑up visits, and clinical outcomes related to severe infection will be captured through review of medical records.