does glp 1 change your metabolism GLP-1 and health: Beyond weight loss in the Ozempic era GLP-1 Receptor Agonists | New

doi: 10.1016/j.phrs.2023.107033 125 HaoBLinSLiuHXuJChenLZhengTet al

When complications arise or results plateau, you're left without medical expertise to adjust your protocol

Treatment duration depends on your medical indication, individual response, and health goals

However, whether LT4 administration is also able to restore FT3 values and whether decrements in FT3 that remain within the reference range are actually of any clinical significance is a matter of controversy (28, 38)

These agents are extensively utilized in managing T2DM and obesity and have demonstrated efficacy in reducing nonfatal myocardial infarction, stroke, and mortality in affected patients.57,59 Exenatide, a synthetic peptide with 50% sequence homology to GLP-1, is resistant to dipeptidyl peptidase-4-mediated degradation54 and was the first GLP-1RAs approved by the US Food and Drug Administration (FDA) for T2DM treatment in 2005.47 Prior to the advent of tirzepatide, a dual GLP-1/GIP receptor agonist, GIP was not considered therapeutically valuable.55,60 Compared to semaglutide and dulaglutide, tirzepatide has demonstrated superior reduction in glycated hemoglobin (HbA1c) and body weight.55 Although tirzepatide binds to the GIP receptor, its affinity for the GLP-1 receptor is approximately fivefold lower than that of endogenous GLP-1.61 Activation of GLP-1 and GIP receptors stimulates insulin secretion from pancreatic beta cells in response to postprandial elevation in plasma glucose, and this effect is markedly attenuated under normoglycemic conditions, thereby mitigating the risk of hypoglycemia associated with GLP-1RAs therapy.55 Furthermore, GLP-1RAs promote beta cell proliferation and inhibit apoptosis.58 GIP receptors are expressed on the alpha cells of islets, whereas approximately 1015% of alpha cells express GLP-1 receptors.62 GLP-1 receptor activation inhibits glucagon secretion, whereas GIP receptor activation increases glucagon secretion during normoglycemia or hypoglycemia, but suppresses glucagon secretion under hyperglycemic conditions.63 Gastric emptying significantly influences postprandial glycemic responses and represents a therapeutic target for diabetes management.64 The glucose-lowering effects of GLP-1RAs are predominantly attributed to their modulation of gastric emptying rather than their direct pancreatic effects.54 GLP-1 receptor activation delays gastric emptying by inhibiting gastric peristalsis and increasing pyloric sphincter tone,65 and this effect is more pronounced in individuals exhibiting rapid baseline gastric emptying.66 The vagus nerve mediates GLP-1s influence on gastrointestinal motility,67 as evidenced by the absence of gastric emptying delay in patients who have undergone vagotomy.68 GLP-1 receptors located in the gastric mucosa regulate insulin secretion but do not affect gastric motility.69 Conversely, GLP-1 receptors in the myenteric plexus activate nitrergic and cyclic AMP signaling pathways to inhibit vagal activity within the gut,70 resulting in decreased phasic gastric contractions, delayed gastric emptying, reduced gastric acid secretion, and increased fasting and postprandial gastric volumes.71 The effect of GLP-1RAs on gastric emptying varies according to the frequency and duration of exposure