The safety and tolerability of GLP-1 receptor agonists in the treatment of type-2 diabetes

Int J Clin Pract. 2010 Sep;64(10):1402-14. doi: 10.1111/j.1742-1241.2010.02465.x.


Established therapies for type-2 diabetes effectively reduce blood glucose, but are often associated with adverse effects that pose risks to patient's health or diminish adherence to treatment. Weight gain, hypoglycaemia and gastrointestinal symptoms are commonly reported and some agents may not be safe for use in patients with renal impairment or elevated cardiovascular risk. New treatments based on the action of the endogenous human hormone glucagon-like peptide-1 (GLP-1), including exenatide and liraglutide, are available. These therapies provide a novel pharmacological approach to glycaemic control via multiple mechanisms of action, and accordingly exhibit different safety and tolerability profiles than conventional treatments. GLP-1 receptor agonists stimulate insulin release only in the presence of elevated blood glucose and are therefore associated with a fairly low risk of hypoglycaemia. Gastrointestinal symptoms are common but transient, and there appears to be little potential for interaction with other drugs. GLP-1 receptor agonists are associated with weight loss rather than weight gain. As protein-based therapies, these agents have the potential to induce antibody formation, but the impact on efficacy and safety is minor. GLP-1 receptor agonists thus offer a new and potentially useful option for clinicians concerned about some of the common adverse effects of type-2 diabetes therapies.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Chemical and Drug Induced Liver Injury / etiology
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Drug Interactions
  • Gastrointestinal Diseases / chemically induced
  • Glucagon-Like Peptide 1 / agonists*
  • Glucagon-Like Peptide-1 Receptor
  • Heart Diseases / chemically induced
  • Humans
  • Hypoglycemia / chemically induced
  • Hypoglycemic Agents / adverse effects*
  • Hypoglycemic Agents / pharmacology
  • Incretins
  • Insulin / adverse effects
  • Kidney Diseases / chemically induced
  • Pancreatitis / chemically induced
  • Receptors, Glucagon / agonists*
  • Sulfonylurea Compounds / adverse effects
  • Thiazolidinediones / adverse effects
  • Thyroid Diseases / chemically induced


  • GLP1R protein, human
  • Glucagon-Like Peptide-1 Receptor
  • Hypoglycemic Agents
  • Incretins
  • Insulin
  • Receptors, Glucagon
  • Sulfonylurea Compounds
  • Thiazolidinediones
  • Glucagon-Like Peptide 1