Treating patients with diabetes of long duration: GLP-1 receptor agonists and insulin in combination

J Am Osteopath Assoc. 2014 May;114(5 Suppl 2):S22-9. doi: 10.7556/jaoa.2014.086.


Patients with long-standing type 2 diabetes mellitus (T2DM) can be clinically challenging for physicians to treat because these patients often lack sufficient β-cell function to respond to some oral glucose-lowering agents, may have profound comorbidities, and may have renal impairment that limits the use of traditional agents. These complications, in addition to older age, also increase the risk of hypoglycemia, which can be a major barrier to treatment success. Individualizing treatment targets to balance the benefits of glycemic control with risks of hypoglycemia is the first step to successfully treating these patients. Careful selection of combination therapy strategies to address limited β-cell function, renal function, and cardiovascular status, along with attention to selection of agents associated with lower risk of hypoglycemia, is important. Basal insulin analogs are often used in patients with long-standing diabetes to address insulinopenic states. Incretin-based therapies, particularly GLP-1 receptor agonists, provide postprandial control with lower risks of hypoglycemia than prandial insulin. The author discusses the management of patients with long-standing diabetes who may have limited β-cell function and require transition to insulin therapy with gradual intensification.

Publication types

  • Review

MeSH terms

  • Blood Glucose / drug effects
  • Blood Glucose / metabolism*
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Drug Therapy, Combination
  • Glucagon-Like Peptide-1 Receptor
  • Glycated Hemoglobin A / metabolism
  • Humans
  • Hypoglycemic Agents / therapeutic use*
  • Insulin / therapeutic use*
  • Receptors, Glucagon / agonists*
  • Receptors, Glucagon / blood
  • Time Factors
  • Treatment Outcome


  • Blood Glucose
  • GLP1R protein, human
  • Glucagon-Like Peptide-1 Receptor
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Insulin
  • Receptors, Glucagon