Glucagon-like peptide-1 based therapies: Effects beyond blood glucose control

Abstract

Therapies based on the gut-derived glucagon-like peptide-1 (GLP-1) are a recent addition to the treatment of Type 2 diabetes. They are either inhibitors of the enzyme DPP-4, which inactivates GLP-1, or analogues of GLP-1 that are resistant to enzymatic degradation. Clinical trials show that long-term treatment with these classes of drugs have a favourable impact on the patient’s lipid profile, reduce systolic blood pressure and reduce abdominal obesity, suggesting a significant cardiovascular benefit in addition to glycaemic control. Transient nausea and vomiting are common adverse effects with this class of drugs and may occur due to reduction in gastric motility. GLP-1 based drugs might be associated with a slight increase in the risk of acute pancreatitis, but there is no evidence that these drugs cause pancreatic cancer in humans. GLP-1 based therapy induces medullary thyroid cancer in rat models, but there is no evidence of it increasing the risk in humans. In animal models, GLP-1 and its analogues improve markers of diabetic nephropathy and diabetic neuropathy by modulating inflammatory pathways. In a rat model of diabetes, GLP-1 analogues preserve pancreatic beta cell function and beta cell mass. On-going studies are investigating whether these benefits are replicated in humans. GLP-1 based drugs have a favourable effect on cardiovascular risk factors. They should be used with caution in patients at risk of pancreatitis. Animal studies suggest improvement in microvascular complications of diabetes.