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Diabetes Myth Buster: DPP4 Inhibitors vs GLP-1 Agonists

November 26, 2013

Incretin based therapies (IBT) continue to grow in popularity as a preferred treatment option for people with type 2 diabetes (T2D). However, it is still common to find confusion between the 2 classes of drugs included in the IBT category. Glucagon-like peptide -1 (GLP1) agonists and dipeptidyl peptidase -4 (DPP4) inhibitors have been part of the diabetes armamentaria for over 8 years. Yet many healthcare professionals remain unclear of the differences and similarities between these 2 agents. Incorrectly, DPP4 inhibitors have been referred to as the oral version of a GLP-1 agonist. This is not true.


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GLP-1 is an incretin hormone or gut hormone, which is secreted from the intestinal cells in response to nutrient stimulus, primarily glucose. People with T2D have diminished levels of endogenous GLP-1, which results in:

  • Increased gastric emptying
  • Decreased glucagon suppression that results in increased hepatic gluconeogenesis
  • Glucose mediated insulin secretion
  • Decreased satiety.

It is not uncommon for people with T2D to complain they are always hungry and never feel full after eating.

Currently, there are 2 approaches to enhancing GLP-1 in an effort to correct the deficiency.  Oral DDP-4 inhibitors reduce the degradation of endogenous GLP-1, thereby providing physiologic concentrations of the GLP-1 hormone. Alternatively, injectable GLP-1 receptor agonists provide exogenous GLP-1 hormone in supraphysiologic concentrations.

Because these mechanisms of actions are separate and distinct, both classes of IBT agents exhibit similarities and differences. Since DPP-4 inhibitors enhance endogenous GLP-1, they primarily effect glucagon suppression and insulin secretion. Whereas, GLP-1 agonists promote the same effects as DPP4 inhibitors, while also slowing gastric emptying and increasing satiety, due to their enhanced physiological characteristics.

Since GLP-1 agonists are 6 to 10 times greater than endogenous GLP-1 levels and slow GI motility, nausea and possibly vomiting are the most common side effects; especially if the patient does not change (decrease) their usual food intake. The nausea and vomiting can also be minimized by slow titration of the GLP-1 agonist from starting dose to therapeutic dose. Weight loss is often observed in patients taking GLP-1 agonists; an adverse drug effect, especially beneficial for overweight or obese T2D people. DPP-4 inhibitors, on the other hand, have minimal adverse effects. The most noteworthy are nasopharyngitis, headache, and upper respiratory infections. Since, DPP-4 inhibitors do not affect GI motility, they promote a weight neutral effect, which is still beneficial for most people with T2D.

DPP-4 inhibitors primarily target the postprandial plasma glucose (PPG), whereas, GLP-1 receptor agonists target fasting plasma glucose (FPG) as well as PPG. This is the reason a higher A1c lowering effect is observed with GLP-1 agonists, due to the FPG lowering effect.

Both drug classes have low hypoglycemic risk when used as monotherapy or in combination with non-secretagogues or insulin. Recent studies have demonstrated favorable cardiovascular outcomes; particularly, decreased systolic blood pressure and decreased triglyceride levels in both DPP-4 inhibitors and GLP-1 agonists.

Clearly both classes are treatment options for people with T2D, however, both are unique in their mechanism of action, adverse drug effect profile, and A1c lowering ability. Therefore, DPP-4 inhibitors should not be referred to as the oral version of GLP-1 agonists.

What has been your experience with these classes? Do you feel that patients are getting the correct prescriptions ordered?


Susan Cornell, PharmD, CDE, FAPhA, FAADE, is an Associate Professor of Pharmacy Practice and Assistant Director of Experiential Education at the Midwestern University Chicago College of Pharmacy. She is also a clinical pharmacist/certified diabetes educator with Dupage Community Clinic in Wheaton, IL.


The views expressed on this blog are solely those of the author and do not necessarily reflect the views of Pharmacy Learning Network or other Pharmacy Learning Network authors. Blog entries are not medical advice.


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