DPP-4 Inhibitors

If you have not already done so, please read my introduction page (HERE)..



So, before we get into just how this drug works, we need to understand some important concepts and answer the question, “what are incretins?”  We have a lot to cover, so let’s get started.

Incretins are hormones in the gut.  The gut plays an important role in blood glucose regulation.  As the glucose levels in the blood rise, the gut responds by releasing a hormone (incretin) called GLP-1 (glucagon-like-peptide-1).  GLP-1 works in two different ways.  First, it stimulates the increase of insulin in the pancreas.  This release is “glucose-dependent” meaning that it only goes into action when glucose begins to elevate.  (In other words, it does not increase insulin when not needed). Next, GLP-1 inhibits the production of glucagon.  Glucagon tells the liver to release some of its stored glucose.  Therefore, GLP-1 ensures that stored glucose will not be released when it is not needed.  When GLP-1 is done doing its job, an enzyme called DPP-4 (dipeptidyl peptidase 4), breaks down this hormone and essentially removes it from the body.

How does a DPP-4 Inhibitor work?  Well, an “inhibitor” is something that “inhibits” something else, or works against something else.  So, a DPP-4 “inhibitor” blocks the action of DPP-4.  So, if DPP-4 is inhibited, or prevented from acting, the GLP-1 hormone can remain longer and exert its blood glucose lowering effects more effectively.  This class of drug is often referred to as an “incretin enhancer” as it enhances or improves the action of gut hormones.

Because of prolonging the action of gut hormones, it also contributes to delayed gastric emptying.  This often promotes a feeling of satiety, which for some, can assist with weight loss.

There is also a significantly decreased likelihood of hypoglycemia with use of this drug class as, once again, its action is glucose-dependent.  Meaning, it will not contribute to increased insulin when not needed.  Therefore, hypoglycemia is rare.

Although it would seem that a drug in this class could be used for people with Type 1, it is not approved for such use.   This drug class is targeted toward treatment of Type 2 diabetes only.

This drug has an average A1c lowering capability of 0.6 – 0.8% (1).

Drugs in this class: Januvia (sitagliptin), Onglyza (saxagliptin), Tradjenta (linagliptin) and Nesina (alogliptin).

These drugs are also included in combination with metformin (Januvia + metformin = Janumet / Onlgyza + metformin = Kombiglyze / Tradjenta + metformin = Jentadueto / Nesina + metformin = Kazano)

One of these drugs is also included in combination with SGLT-2 inhibitors (Tradjenta + Jardiance = Glyxambi)

Common Precautions: Dosage may need to be reduced in the case of renal insufficiency.  Renal (kidney) function should be regularly monitored (linagliptin is often used in renal insufficiency as it is excreted through the digestive tract versus through the kidneys).  Common side effects include upper respiratory infections, nasopharyngitis, headaches.

Serious Precautions:  Can contribute to pancreatitis.  Report any incidences of abdominal pain, nausea or vomiting to your primary healthcare provider immediately.  There has also been more recent reports of increased risk of heart failure.  Therefore, if you experience swelling, fluid retention or shortness of breath, seek immediate medical help.

My Opinions

If you are only interested in the facts about this drug and how it works, feel free to stop here.  The following are my concerns with this drug class and my personal opinions.


Please note, in providing my personal opinions with concerns for these medications, once again, these are my opinions only and not intended as advice for you personally.  Please consult your personal healthcare provider to discuss the benefits and risks of any medications prescribed for you.

So, here are my thoughts.

REMEMBER, above all, diabetes is a problem of GLUCOSE INTOLERANCE.  The answer to that problem is not “take in all the glucose you want and then take a drug to deal with the glucose overload.”  That is like telling someone with lactose intolerance to “eat all the milk and cheese you want and we’ll give you a pill to try and make it better.”  No!  People with lactose intolerance are told not to eat milk and cheese.  It is the same with diabetes.  People with diabetes should consume as little of the foods that turn quickly into glucose as possible.  Then, there will be little need for pills to deal with the excess glucose.

As you know, I recommend a low carb lifestyle for all people, but PARTICULARLY as a first line of defense in the treatment of diabetes, NOT drug therapy.

(Why A Low Carb Diet Should Be the FIRST Approach in the Treatment of Type 2 Diabetes HERE.  Low Carb Diet Recommended for Type 1 and Type 2 Diabetes HERE.)

I believe that drug therapy has it’s place, but ONLY to address any issues after a healthy, low carb lifestyle, exercise and other lifestyle practices are ALREADY in place.  So, if you are already practicing these things, there may not be a need for this type of medication.  Keep in mind, the A1c lowering capability of this drug is extremely poor when compared to low carb.  You could probably achieve the same A1c lowering affects as this drug after practicing a low carb lifestyle for just a few weeks.  And with the potential serious health risks, just seems logical to avoid this drug class.

Once again, this is my personal opinion.

To further my opinion, I would not personally feel comfortable taking any drug in this class.  There ARE medications that I would take to treat diabetes if my low carb healthy lifestyle was not enough to control my blood glucose.  None of the drugs in this class are among those I would consider.

Here is an extremely well-researched article by a website which I highly respect, expressing additional concerns about this drug class HERE.