Study reveals untapped potential of liraglutide in post-stroke brain protection

 Didn't your competent? doctor put together protocols on this already? NO? So, well over a decade of incompetence along with the board of directors not having proper goals and objectives for stroke staff!

liraglutide (6 posts to April 2012)

Study reveals untapped potential of liraglutide in post-stroke brain protection

Highlight

In a randomized controlled trial involving 636 Chinese patients with type 2 diabetes and minor acute ischemic stroke or high-risk transient ischemic attack, liraglutide treatment significantly reduced stroke recurrence at 90 days (7.9% versus 13.8%) and improved functional outcomes.

Background

• Type 2 diabetes is a primary risk factor for ischemic cerebrovascular disease, with approximately 33% of stroke individuals having diabetes, resulting in an elevated residual risk of recurrence.

• Among patients with minor acute ischemic stroke who have type 2 diabetes, the 90-day recurrence rate is 12.8%, and intensive glycemic control through insulin or sulfonylureas does not substantially reduce the risk of macrovascular complications.

• Glucagon peptide-1 (GLP-1) receptor agonists stimulate insulin release in a glucose-dependent manner and inhibit glucagon secretion by the pancreas, as well as improve insulin resistance and reduce inflammatory responses.

• Although GLP-1 receptor agonists reduce the incidence of major adverse cardiovascular events in patients with type 2 diabetes at high cardiovascular risk, there is still insufficient evidence on their efficacy in preventing stroke recurrence and improving outcomes during the acute phase of ischemic stroke.

Liraglutide, a GLP-1 receptor agonist widely used for the treatment of type 2 diabetes, promotes weight loss and offers protection against macrovascular and microvascular complications in patients with diabetes.

Methodology

A total of 636 patients (median age 63.5 years [IQR 57.8-70]; 231 women [36.3%]) were enrolled in this multicenter, controlled, prospective, randomized, open-label, blinded outcome trial conducted in 27 hospitals in China.

• Participants with type 2 diabetes who had minor acute ischemic stroke (National Institutes of Health Stroke Scale score <3) or high-risk transient ischemic attack (ABCD² score ≥4) were randomized within 24 hours of symptom onset.

Patients in the liraglutide group received the drug once daily for 90 days (0.6 mg in the first week, increasing to 1.2 mg in the second week, and followed by 1.8 mg until day 90) in addition to standard therapy, while the control group received only standard treatment as per established guidelines.

• The primary endpoint was recurrence of stroke (ischemic or hemorrhagic) after 90 days, and the safety endpoint was symptomatic intracranial hemorrhage and all-cause mortality at 90 days.

Key Information

• At 90 days, 25 patients (7.9%) in the liraglutide group and 44 (13.8%) in the control group had stroke recurrence (risk ratio [RR] 0.56; 95% confidence interval [CI], 0.34-0.91; P = 0.02).

• A significantly higher proportion of patients in the liraglutide group (274 [87.3%]) compared to the control group (246 [77.8%]) achieved excellent functional outcomes (odds ratio [OR] of 1.95; 95% CI, 1.28-3.00; P = 0.002).

• The rates of symptomatic intracranial hemorrhage and all-cause mortality were low and similar between the groups.

• New clinical vascular events at 90 days occurred in 27 of 317 patients (8.5%) in the liraglutide group and in 50 of 319 patients (15.7%) in the control group (RR of 0.53; 95% CI, 0.33-0.84; P = 0.01).

In practice

"Patients receiving liraglutide had a lower risk of recurrent stroke and a higher rate of excellent functional outcomes (MRS score <1) at 90 days, with no increase in the incidence of symptomatic intracranial hemorrhage or mortality. In line with previous studies, the stroke recurrence rate and neurological outcomes at 90 days observed in the control group were very close to those reported in similar patient populations, thus strengthening the external validity of the present findings," the study authors wrote.

Source

The study was led by Dr. Huili Zhu, MD, of the Affiliated Hospital of the First University of Jinan in Guangzhou, China. It was published online Nov. 3 in the journal JAMA Internal Medicine.

Limitations

Early discontinuation of the study introduced uncertainty in the observations and increased the risk of not detecting a treatment effect. Although an effect of the treatment has been observed, its external validity and the possibility of generalization to broader populations remain uncertain. In addition, the possibility of information bias cannot be ignored, as the assigned treatment was not hidden by participants or clinicians, although masked assessments of outcomes were used to minimize measurement bias. The generalizability of current results is limited by the exclusion criteria, which excluded patients without type 2 diabetes, those with ischemic stroke (National Institutes of Health Stroke Scale >3 score), subjects with stroke of cardiac origin, patients who started treatment within 24 hours of symptom onset, and patients undergoing or planning to undergo thrombolysis or thrombectomy. Because the study included only Chinese patients, the results may not apply to other populations. The pre-specified protocol did not include the collection of standardized laboratory follow-up data on glycated hemoglobin levels or body mass index at 90 days, making it impossible to explore whether improvements in long-term glycemic control or weight reduction contributed to the observed effects of treatment.

Conflicts of interest

The study was funded by the Guangzhou Science and Technology Program (202002020003, 202201020070, 2023A03J1023 and 2023A03J1022). Researchers Dr. Huili Zhu, Dr. Bin Yang, and Dr. Anding Xu reported receiving grants from the Guangzhou Science and Technology Program while conducting the study. The funding organizations had no role in the design and conduct of the study; in the collection, management, analysis and interpretation of data; in the preparation, revision or approval of the manuscript; nor in the decision to submit the manuscript for publication.

This content was produced using a variety of editing tools, including artificial intelligence (AI), as part of the process. Human editors reviewed this content prior to publication.