Type 2 diabetes: What are the advantages and disadvantages of exenatide injections?

In type 2 diabetes, using exenatide injections together with oral antidiabetics can achieve target blood sugar levels as effectively as using insulin. Exenatide can also help reduce weight a little. However, adverse effects are common.

In type 2 diabetes, the body either does not produce enough insulin, or has become resistant to its own insulin and it no longer has the effect it should. As a result, blood sugar levels are too high, a condition called hyperglycemia. Typical symptoms include being thirsty, tired, going to the toilet a lot and itching. The bigger problem, though, is that over the years, very high blood sugar levels damage the blood vessels and therefore important organs like the eyes and kidneys.

While many people with type 2 diabetes manage to keep their blood sugar levels at a low enough level without medication, others take tablets called oral antidiabetics to control their hyperglycemia. You can read more about type 2 diabetes and the medications that can be used for this condition in our fact sheet.

People with type 2 diabetes usually do not need insulin, unlike people with type 1 diabetes who have to inject insulin every day. However, if other strategies are not enough to keep blood sugar levels under control, then insulin therapy will be necessary. While many people can adjust well to injecting insulin, others would like to try out another option before deciding to use insulin.

The new drug exenatide

Exenatide is a new hormone-like medication called an “incretin mimetic” that has been available in Germany since 2007. Exenatide is not meant to replace antidiabetic tablets. It is an injection that is used twice a day as an add-on therapy to oral diabetes medications containing metformin and/or sulfonylurea, making it an alternative to insulin treatment. Exenatide comes in a pre-filled dosing pen that injects the drug under the skin (subcutaneous injection). Only one brand of exenatide (called “Byetta”) is currently on the market in Germany.

Experts believe that exenatide helps the body to make more insulin by increasing the activity of insulin-producing beta cells in the pancreas. It is also assumed to keep food in the stomach longer, reduce appetite and inhibit the release of sugar into the bloodstream.

Exenatide was developed with the aim of causing fewer episodes of low blood sugar than insulin. This is called hypoglycemia and is a common adverse effect of insulin therapy. It happens when there is too much insulin in the body. This leads to the blood sugar dropping to a dangerously low level, which can result in shaking, confusion and even loss of consciousness. However, the drug is new, so there are still many unanswered questions about its long-term effects.

Analyzing the research on exenatide

Researchers from the German Institute for Quality and Efficiency in Health Care (IQWiG) looked for trials that tested the effects of exenatide as an add-on therapy for people with type 2 diabetes. The trials were only included in the analysis if they compared a group of people who had exenatide with a group of people who took a placebo (dummy treatment) or insulin. By doing these kinds of trials, researchers can learn about the advantages and disadvantages of a treatment.

IQWiG searched medical databases and asked the manufacturers of the drug if there were any extra trials. They found find five randomized controlled trials that compared exenatide as an add-on therapy with either a placebo or insulin. That means that all of the participants in the trials were using oral antidiabetics, and one group of people had exenatide injections as well, while another group used a placebo or insulin in addition to their tablets.

A total of 2,500 men and women took part in the trials. In three of the trials exenatide was compared with a placebo, and in the other two it was compared with insulin. The trials lasted between six months and one year. This means that they were long enough to test whether the new drug can reduce blood sugar levels, but not long enough to know what the long-term effects are. These include both long-term safety and whether or not using this drug can prevent the long-term complications of diabetes, like damage to the kidneys or eyes.

Advantages and disadvantages of exenatide

The researchers concluded that 10-microgram doses of exenatide used with oral antidiabetics have a similar influence on blood sugar levels to insulin. However, the trials did not provide enough information to know whether or not exenatide causes fewer episodes of low blood sugar than insulin does.

The main adverse effects of exenatide involved the digestive system: nausea was the most common. Compared to placebo, an extra 2 out of every 10 people felt nauseous if they had exenatide injections (20%), and an extra 1 out of every 10 vomited (10%). About 1 out of every 10 people using exenatide stopped taking it because of adverse effects. Compared to insulin, exenatide also caused more adverse effects like nausea and vomiting. Further research will be needed to find out in what cases people with type 2 diabetes could use exenatide rather than insulin.

In all the trials, people who had exenatide injections lost a kilogram or two of weight (about 2.2 to 4.4 pounds) when compared to participants taking placebos. These were partly the same people who had adverse effects such as nausea. But the weight loss is probably not due to the adverse effects of exenatide alone. The men and women who injected insulin put on about one or two kilos on average. Trials that follow people up for several years are needed to find out whether the weight loss associated with taking exenatide has a health benefit.

Towards the end of 2007, both the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) reported that some of the people taking exenatide were experiencing acute pancreatitis, a very painful and potentially life-threatening inflammation of the pancreas. The pancreas is an organ just below the stomach where digestive enzymes and insulin are produced.

Typical symptoms of acute pancreatitis include severe, usually belt-like abdominal pain, often accompanied by vomiting. The FDA and EMA advise people to seek immediate medical attention if they have these symptoms while they are taking exenatide. A warning was added to the package insert and to the summary of product characteristics. In August 2008 the FDA updated this warning because two people who were taking exenatide died from a particularly severe form of pancreatitis.

In November 2009 the FDA also announced that information on altered kidney function was added to the package insert. The FDA reported that there were cases of kidney problems like renal failure and insufficiency associated with exenatide. They recommend to see a doctor if symptoms such as nausea, loss of appetite, swollen lower legs or changes in color and amount of urine are noticed. For more information on how the kidneys work click here.

IQWiG’s researchers concluded that it is early days for research on exenatide. There are currently several additional trials underway, so more information on this new antidiabetic drug is expected in the near future. If you want to know more about the treatment options for type 2 diabetes, you can read about them here.

Author: Institute for Quality and Efficiency in Health Care (IQWiG)


(The update only contains the new FDA recommendations from November 2009. Other information on the advantages and disadvantages of exenatide has not been updated.)


Note

This health information is a summary of a scientific report published by IQWiG. It is not an assessment of the right to have health care services paid for by statutory health insurance funds in Germany. By law, decisions about paying the costs for diagnostic and therapeutic procedures can only be made by the German Federal Joint Committee (G-BA). The Federal Joint Committee takes IQWiG reports into consideration in its decision-making process. You can find information about the decisions of the German Federal Joint Committee on its English-language website, www.english.g-ba.de.

© IQWiG (Institute for Quality and Efficiency in Health Care)