Journal of Diabetology

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Commentary - Journal of Diabetology (2025) Volume 9, Issue 1

GLP-1 Receptor Agonists: A Breakthrough in Type 2 Diabetes Management

Saran Mah*

Department of General Surgery, Harvard Medical School, Canada

*Corresponding Author:
Saran Mah
Department of General Surgery
Harvard Medical School, Canada
E-mail: srnmh@ices.on.ca

Received: 01-Mar-2025, Manuscript No. AADY-25-166639; Editor assigned: 03-Mar-2025, PreQC No. AADY-25-166639(PQ); Reviewed: 16-Mar-2025, QC No. AADY-25-166639; Revised: 22-Mar-2025, Manuscript No. AADY-25-166639(R); Published: 25-Mar-2024,DOI:10.35841/aady-9.1.248

Citation: Mah S. GLP-1 receptor agonists: A breakthrough in type 2 diabetes management. J Diabetol. 2025;9(1):248

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Introduction

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by insulin resistance, impaired insulin secretion, and progressive beta-cell dysfunction. Managing T2DM effectively remains a global challenge due to its complexity and the risk of serious complications such as cardiovascular disease, nephropathy, neuropathy, and retinopathy. Over the past decade, a class of drugs known as GLP-1 receptor agonists (GLP-1 RAs) has emerged as a transformative treatment option, offering significant benefits beyond glycemic control.

Glucagon-like peptide-1 (GLP-1) is an incretin hormone secreted by intestinal L-cells in response to nutrient intake. It enhances glucose-dependent insulin secretion, suppresses glucagon release, slows gastric emptying, and promotes satiety, leading to reduced food intake. However, native GLP-1 is rapidly degraded by the enzyme dipeptidyl peptidase-4 (DPP-4), limiting its therapeutic potential [1].

GLP-1 receptor agonists are synthetic analogues of GLP-1 that resist degradation by DPP-4, enabling prolonged activity. They bind to and activate the GLP-1 receptor on pancreatic beta cells and other target tissues, amplifying the natural effects of GLP-1. These agents include exenatide, liraglutide, dulaglutide, semaglutide, and others, with varying durations of action and administration routes.

By stimulating insulin secretion in a glucose-dependent manner, GLP-1 RAs reduce fasting and postprandial blood glucose levels without causing significant hypoglycemia. They also suppress inappropriate glucagon secretion, which contributes to hyperglycemia.

Unlike many traditional antidiabetic drugs that cause weight gain, GLP-1 RAs promote satiety and reduce appetite, resulting in significant weight loss. This is particularly beneficial since obesity is a major risk factor and common comorbidity in T2DM patients. Several large-scale cardiovascular outcome trials (CVOTs) have demonstrated that GLP-1 RAs reduce major adverse cardiovascular events (MACE), including heart attack and stroke, especially in patients with established cardiovascular disease. This has positioned GLP-1 RAs as preferred agents for diabetic patients at high cardiovascular risk. Emerging evidence suggests that GLP-1 RAs may exert renoprotective effects by reducing albuminuria and slowing the progression of diabetic kidney disease. Experimental studies indicate GLP-1 RAs may help preserve pancreatic beta-cell function, potentially slowing disease progression [2].

Clinical trials have confirmed the efficacy and safety of GLP-1 RAs. For example, the LEADER trial (Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results) showed that liraglutide significantly reduced cardiovascular death by 22% compared to placebo. Similarly, the SUSTAIN-6 trial demonstrated that semaglutide lowered the risk of cardiovascular events while also providing robust glycemic control and weight loss.

Meta-analyses of GLP-1 RAs indicate they reduce HbA1c levels by approximately 1.0-1.5%, often more than many other oral antidiabetic agents. Weight loss typically ranges from 2 to 6 kilograms, improving insulin sensitivity and metabolic profiles. GLP-1 RAs are primarily administered via subcutaneous injection, ranging from twice daily to once weekly dosing, depending on the agent. Recently, an oral formulation of semaglutide has also been approved, enhancing patient convenience [3].

The most common side effects include gastrointestinal symptoms such as nausea, vomiting, and diarrhea. These tend to be mild to moderate and improve over time. Rare but serious adverse events include pancreatitis and potential risk of medullary thyroid carcinoma, although these are uncommon and require monitoring.

Due to their comprehensive benefits, GLP-1 RAs are now strongly recommended by international diabetes associations such as the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). For patients with T2DM and cardiovascular disease or at high cardiovascular risk, GLP-1 RAs are considered first-line injectable therapy after metformin, ahead of insulin or other agents [4].

Ongoing research is expanding the scope of GLP-1 RAs. Studies are exploring combination therapies with other incretin-based drugs, dual or triple receptor agonists targeting GLP-1 and other pathways, and potential benefits in other metabolic conditions such as non-alcoholic fatty liver disease (NAFLD). The development of longer-acting formulations and non-injectable delivery methods will further enhance patient adherence and broaden the applicability of this drug class [9, 10].

Conclusion

GLP-1 receptor agonists represent a major breakthrough in the management of type 2 diabetes. Their ability to improve glycemic control, promote weight loss, and reduce cardiovascular risk has transformed the therapeutic landscape. As understanding of their mechanisms deepens and newer agents become available, GLP-1 RAs are poised to remain central in personalized diabetes care, improving outcomes and quality of life for millions of patients worldwide.

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