Glucagon-Like Peptide-1 Receptor Agonists in Primary Care: Beyond Glycemic Control

Review Article

J Fam Med. 2023; 10(1): 1325

Glucagon-Like Peptide-1 Receptor Agonists in Primary Care: Beyond Glycemic Control

La Salle J1#, Uusinarkaus K2#, Marso SP3 and Pantalone KM4*

1Family Medicine, The Excelsior Springs Clinic, MO, USA

2Family Medicine, CHPG Primary Care, CO, USA

3Cardiovascular Medicine, HCA Midwest Health, KS, USA

4Department of Endocrinology, Diabetes and Metabolism, Cleveland Clinic, OH, USA

#These authors have contributed equally to this article.

*Corresponding author: Pantalone KM Department of Endocrinology, Diabetes, and Metabolism, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA Email: [email protected]

Received: October 26, 2022; Accepted: November 23, 2022; Published: February 22, 2023


Type 2 diabetes (T2D) is no longer considered solely a glucose-centric condition, but rather a chronic cardiometabolic disease that is linked to premature cardiovascular and renal complications and early death. Whereas previously, the level of glycemic control drove management decisions regarding treatment intensification, healthcare providers now have newer classes of agents that not only effectively lower glucose levels but also reduce the long-term risk of cardiovascular and renal complications. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) address several of the progressive multiorgan dysfunctions associated with T2D and a number of GLP-1RAs have been shown to reduce the risk of major adverse cardiovascular events in people with established cardiovascular disease or in those at high cardiovascular risk; GLP-1RAs (or a cardioprotective sodium-glucose cotransporter-2 inhibitor) should be considered in these high-risk patients regardless of their glycated hemoglobin goal attainment status. GLP-1RAs also facilitate substantial weight loss and there is some evidence that they may help to restore β-cell function and slow the decline of kidney function, although further studies are needed to confirm this.

Keywords: β-cell Preservation; Cardiovascular Disease Risk; Glucagon-Like Peptide-1 Receptor Agonist (GLP-1RA); Renal Function/Dysfunction; Type 2 Diabetes (T2D); Weight Control/Management

Abbreviations: CI: Confidence Interval; CV: Cardiovascular;DPP4i: Dipeptidyl Peptidase-4 Inhibitor; eGFR: estimated Glomerular Filtration Rate; ER: Extended-Release; GLP-1: Glucagon-Like Peptide-1; GLP-1RA: Glucagon-Like Peptide-1 Receptor Agonist; HR: Hazard Ratio; LV: Left Ventricular; MACE: Major Cardiovascular Adverse Events; s.c.: subcutaneous; SGLT2i: Sodium-Glucose Cotransporter-2 Inhibitor; SU: Sulfonylurea; T2D: Type 2 Diabetes; TZD: Thiazolidinedione


Historically, the focus for patients with type 2 diabetes (T2D) has been the prevention of chronic hyperglycemia using lifestyle and dietary changes, plus glucose-lowering medications [1]. However, these patients are at risk of long-term complications owing to the effects of dysfunctions covering multiple organs and systems [2-6].

The concept of T2D as a multiorgan disease is summarized by the “ominous octet” of eight main dysfunctions (Figure 1) [2], which typically manifest as an interrelated association between glucose dysregulation, weight gain, dyslipidemia, and blood pressure abnormalities, with progressively increasing cardiovascular risk and renal impairment. Newer glucose-lowering therapies, including glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1RAs), can influence a multitude of these dysfunctions.