Incretin Mimetics Side Effects - Pros & Cons, and How They Work?
blog detail banner

Drug Side Effects

Side effects of Incretin Mimetics (GLP-1 agonists)

Nov 25, 2016

Incretin Mimetics: How they work

Incretins are protein hormones produced in the digestive tract after we have eaten a meal. They lead to an increase in insulin secretion, so the sugar from the meal can be delivered from our blood into our cells, reducing blood sugar levels. Incretin mimetics ‘mimic’ the incretin called GLP-1, so they too lower blood sugar. You need inject incretin mimetics, also known as GLP-1 agonists, under your skin, just before a meal. Side effects of Incretin Mimetics or GLP-1 drugs may be the result of the way they work in the human body.

Incretin Mimetics lower blood sugar in the human body by:

  • Increasing insulin secretion from the pancreas after a meal
  • Reducing the amount of glucagon secreted from the pancreas. Glucagon is a hormone that signals the liver to release stored sugar into the blood stream
  • Reducing the speed at which food is ‘emptied’ into the intestine. This helps you feel fuller for longer and reduces appetite.

Incretin Mimetics: Most Prescribed brands

Three incretin mimetics are most prescribed and sold:

  • Exenatide (Immediate Release), which was the first in this class of drugs and sold under the brand name Byetta
  • Exenatide (Long Acting), sold under the brand name Bydueron
  • Liraglutide, sold under the trade name, Victoza

Other commonly available brand names are Saxenda and Trulicity.

Exenatide is isolated from the saliva of a lizard called Heloderma suspectum. (popularly called the Gila Monster). Exenatide (Immediate Release) or Byetta is sold as as a solution (liquid) in a prefilled dosing pen. You need to inject it just under the skin twice a day, just before meals. It should never be injected after meals. Your doctor will probably start you on a low dose of Exenatide (Immediate Release) and may switch you a higher dose if your blood sugar control does not improve after one whole month.

Exenatide (Long Acting), sold as Bydureon , comes as a powder to be mixed with liquid in a vial or a prefilled dosing pen, to be injected subcutaneously, just once a week.

Liraglutide isn’t found in nature but is artificially synthesized by a process called ‘recombinant DNA technology’ from yeast cells. Liraglutide injection comes as a solution (liquid) in a prefilled dosing pen, to inject under the skin of your stomach, thigh, or upper arm. It is usually injected once a day, at roughly the same time of day, with or without food.

How Should GLP-1 Drugs Be Used

As an injectable, incretin mimetics are used only when oral drugs like metformin and sulfonylureas have failed to do their job in blood sugar control. For many years, diabetics who were unable to control their sugar levels with just oral medication had to resort to insulin shots as the only other option. But this led to one of the most hated side effects of insulin shots – weight gain. By achieving the same sugar control without the weight gain, Incretin mimetics have brought new hope for diabetics.

Incretin Mimetics and Weight Loss

The biggest positive side-effect for patients who are put on Incretin Mimetics is the possibility of weight loss. Where most patients add on pounds when they start insulin shots, many patients lose weight after starting GLP-1 injections. In fact, research shows that people with the highest levels of glucose in their blood often lose the greatest amount of weight after starting incretin mimetics!

Why this happens is not fully clear yet, but researchers are guessing that by keeping food in the stomach for longer, Incretin Mimetics reduce appetite and keep you feeling full for longer, reducing how much you eat. And since incretin mimetics can only work when there is excess glucose in the blood, the worse your diabetes numbers are when you start, the more effective the medication will be.

Another added benefit is that unlike oral medications like metformin or sulfonylureas, GLP-1 drugs never cause low blood sugar or hypoglycemia. Once again, this is simply because if a person does not have excess blood sugar at the point when they inject themselves, the drug will not act to lower the blood sugar further.

Side Effects of Incretin Mimetics: What could happen when you start

Dizziness is one of the side effect of Incretin Mimetics or GLP-1 agonists

Dizziness is one of the side effect of Incretin Mimetics or GLP-1 agonists

Despite all of the benefits we have listed above , incretin mimetics have some undesirable side effects too.

Side Effects of Incretin mimetics Include

  • Constipation
  • Diarrhea
  • Nausea
  • Indigestion
  • Loss of Appetite
  • Abdominal Pains
  • Dizziness
  • Increased Sweating
  • Pain at the site of injection

 Long Term Side Effects of Incretin Mimetics

Ten to twelve years is a relatively short period of time to study the long-term effects of a new class of drugs. Since they were introduced, incretin mimetics have been found to:

  • Increase the risk of pancreatitis, especially in obese type 2 diabetics. If severe abdominal pain is experienced by such patients, they should immediately contact their doctor and stop the medication.
  • Increase the risk of pancreatic cancer
  • Increase the risk of thyroid carcinoma. In study done on rats, the drug was found to make the animals more likely to get thyroid cancer.
  • Increase the likelihood of subclinical inflammation of the pancreas and of the occurrence of neuroendocrine tumors.

Should You Be Having GLP-1 Agonists Over the Long Term?

Research has shown that many prescritpion drugs interfere with the absorption, transport and utilization of essential nutrients in the human body, especially when the drugs are used for a long time. This is called drug-nutrient depletion However, specific nutrient depletion caused by GLP-1 Agonists has not been studied.

Precautions to follow while using Incretin mimetics include:

  • Avoiding excessive alcohol intake, since the risk of pancreatic inflammation is already higher due to the way the drug works in your body. Alcohol heightens this risk.
  • Informing your doctor if you are pregnant or breastfeeding
  • If you’re on incretin mimetics along with other oral anti diabetic drugs, monitoring your blood sugar levels so they don’t dip too low
  • Telling your doctor if you are allergic to any drugs including incretin mimetics
  • Informing your doctor about any other drugs, vitamins, supplements and herbal products that you may be consuming at that time or plan to include in the near future.
  • Informing your doctor if you have to undergo a surgery, even if it’s a dental procedure.

What To Do If You Forget a Dose of Incretin Mimetics?

  • If you forget to take a dose of incretin mimetics, and realize this long before the next dose is due, then you should take the dose right away.
  • However, if you remember only when it is almost time for the next dose, just skip the forgotten dose altogether and proceed with the normal injection routine from thereon. Don’t take a double dose to compensate for one that has been missed.
  • If you forget for a period of up to three days, it is important that you inform your doctor.

With all medicines, especially injectables, it is important to identify why this happened, so that you can prevent recurrences.

There are many reasons one may forget to take a incretin mimetics dose:

  • You may be busy or distracted at the time you are supposed to take them
  • You may have changed your daily routine, or may be in an unfamiliar place
  • You are new to the injections and it is yet to become a habit

You can remember to take your injections on time by keeping them somewhere where you can’t ignore them. Incretin Mimetics are to be injected just before meals, so some people find that keeping them at the center of the dining table helps them remember.

Storage and Disposal of Incretin Mimetics

Here’s a checklist of how to store and dispose incretin mimetics:

  • Before first use, the Byetta liquid should be refrigerated, between 36 degrees Fahrenheit to 46 degrees Fahrenheit.
  • After first use, however, it can be stored at a cool, dry place.
  • Byetta pens need to be protected from light and should never be refrigerated.
  • When travelling, ensure Byetta is stored in a safe, dry place.
  • Dispose of the drug thirty days after the day you open it.
  • Injectables that are not needed should be disposed in such a way that they cannot be accessed by pets, children and other people. Do not flush the drugs down the toilet, use the “medicine take back” program instead.

Dietary Considerations

Being on incretin mimetics gives you a feeling of satiety and so, you eat less. That’s the secret behind the weight loss that comes with this class of drugs. Please remember that all such interventions are ‘self-limiting’. What this means is that you can’t eat very rich foods endlessly and expect only the incretin mimetics to do all the work for you.

Incretin Mimetics: Interactions with other drugs

Interactions with herbal drugs

Most herbal drugs affect the metabolism of incretin mimetics. If you’re taking any herbs, there is the risk that it could interact with the GLP-1 drugs. Always consult your doctor before you start any herbals.

Interactions with other prescription drugs

Make sure that your blood glucose levels are being monitored closely by your doctor, especially when you are on an injectable like incretin mimetics. Diabetics tend to be on multiple medications for complications of diabetes, so again, your doctor can help you navigate this minefield best.

Incretin mimetics: Costs

Incretin mimetics tend to be more expensive than any other treatment for diabetes. Average cost of treatment for all 3 versions ranges from $200-300 for a month. If you have the insurance coverage and your doctor is willing to prescribe them, especially if your blood sugar is not controlled by other oral medications, then you may want to consider them.

Incretin Mimetics: The final verdict

While incretin mimetics have emerged as the first viable alternative to insulin in decades, they are relatively new. For this main reason, doctors today are only using it when other oral medications like metformin or sulfonylureas fail to achieve good blood sugar control.

The increased risks of damage to the pancreas and the likelihood of thyroid cancers is a red flag not to be ignored.

Doctors are increasingly finding that diabetes, as a dietary and lifestyle disorder, responds best to lifestyle interventions. By practicing intermittent fasting, insulin resistance can be reduced. Making exercise a regular part of your daily routine is another huge element of recovery. With these and the proper stress management techniques like yoga and meditation , you can move the needle a long way on your diabetes. Finally, several dietary supplements have been shown to reduce blood sugar levels and help people reverse diabetes.

Nachiket Rajadhyaksha
Nachiket holds a first class degree in Pharmacy and is passionate about writing. He believes that subject experts must simplify medical concepts to make them interesting and accessible to everyone.


  1. Inzucchi SE, et al. (2012). Management of hyperglycemia in type 2 diabetes: A patient-centered            approach. Diabetes Care, 35(6): 1364–1379.
  2. May, M. & Schindler, C. (2017). Clinically and pharmacologically relevant interactions of        antidiabetic drugs. Retrieved 26    January 2017, from
  3. MedIndia,. (2017). Sitagliptin (Januvia Tab) Drug Information – Indications, Dosage, Side           Effects and Precautions | Medindia. Medindia. Retrieved 26 January 2017, from   
  4. MedlinePlus, (2017). Liraglutide Injection: MedlinePlus Drug Information.      Retrieved 26 January 2017, from
  5. Singh S, Chang HY, Richards TM, Weiner JP, Clark JM, Segal JB. Glucagonlike peptide 1-                    based therapies and risk of hospitalization for acute pancreatitis in type 2 diabetes             mellitus: a population-based matched case-control study. JAMA Intern Med 2013 Feb            25:1-6. doi: 10.1001/jamainternmed.2013.2720. [Epub ahead of print].
  6. S. National library of Medicine, MedlinePlus