Treatment with GLP-1 Receptor Agonists

Abstract

The GLP-1 RAs have become popular because of their efficacy and durability in relation to glycemic control and their low risk of hypoglycemia in combination with weight loss in most patients. GLP-1 RAs mimic the effects of native GLP-1, which increases insulin secretion, inhibits glucagon secretion, increases satiety, and slows gastric emptying. Notably, the insulinotropic and glucagonostatic effects are glucose dependent, and therefore the risk of hypoglycemia is very low during treatment with a GLP-1 RA. The effect on gastric emptying is primarily observed with the short-acting GLP-1 RAs, since significant tachyphylaxis for this effect develops after few days’ treatment with the long-acting GLP-1 RAs. The postprandial glucose control mediated by the short-acting GLP-1 RA seems to be primarily explained through the delaying effect on gastric emptying rather than the effect on insulin and glucagon secretion. In addition, GLP-1 RAs reduce blood pressure during chronic treatment, increase pulse rate, and reduce postprandial triglyceride concentrations. Studies have suggested that GLP-1 receptor agonists might have neuroprotective effects. The most common adverse events are nausea and other gastrointestinal discomfort. The drawbacks of the GLP-1 RAs include the subcutaneous administration, the gastrointestinal side effects, and the cost. Several GLP-1 RAs are now licensed for the treatment of type 2 diabetes. However, the intra-class difference raises challenges in relation to individual treatment. In the present chapter, the individual GLP-1 RAs will be presented followed by a head-to-head comparison of GLP-1 RAs. Thereafter, the adverse events and the cardiovascular effects of GLP-1 RAs including the cardiovascular endpoint trials with GLP-1 RAs will be discussed. The efficacy and safety of fixed combination of basal insulin and a GLP-1 RA will be reviewed. The use of GLP-1 RAs in the treatment of patients with type 1 diabetes or in treatment of obesity will also be examined.