A New Kid Moves in on the Diabetes Scene: Injections Besides Insulin

A New Kid Moves in on the Diabetes Scene: Injections Besides Insulin

Within the last half dozen years, injections besides insulin have become available to treat diabetes. They are called incretins. They are similar to a hormone normally found in our “gut” (gastrointestinal tract) called GLP-1, which goes up when we eat.

How Incretins Work

GLP-1 and incretins control blood sugar levels by:

  • Making the pancreas put out insulin, which lowers blood sugar levels.
  • Lowering glucagon, a hormone that also comes from the pancreas. Glucagon levels are usually high in those with Type 2 diabetes and go up with meals. But unlike insulin, glucagon raises blood sugar. So, by lowering glucagon, incretins keep the sugar from going too high.
  • Making the stomach empty slowly. This reduces the rate at which carbohydrate is digested, which keeps sugars from rising quickly after meals.
  • Reducing appetite. This leads to weight loss in the majority of diabetes patients.

Side Effects

Side effects of these drugs are generally limited to nausea. Vomiting sometimes occurs. However, these symptoms usually just happen when starting or adjusting the dosage of medication.

Why do incretins have to be injected and why are they becoming more popular?

Just like normal human intestinal hormones, the incretins are all proteins, which would be digested if they were taken by mouth as pills or liquid. Therefore, incretins must be injected, just like insulin. Many patients resist and are even fearful of injecting medicine whether it is insulin or incretins. Even so, there are many reasons why this new class of anti-diabetes therapies should be considered when treating diabetes:

  • Very little risk of hypoglycemia (low blood sugars)
  • No weight gain, something that most other diabetes treatment drugs—including insulin—may cause. In fact, most patients lose weight when they take incretins.

The ability of the various types of incretin medications to lower blood sugar varies. In general, the very shortacting medicines given twice daily are usually not as effective as the longer-acting once daily and once-weekly medicines. Longer acting versions – liraglutide and exenatide long acting release (LAR) – may lower blood sugar as much or even more than the strongest pill types of medication used to treat type 2 diabetes mellitus. Because these longer-acting incretins are so effective, as well as relatively free from important side effects such as weight gain and hypoglycemia, it has become more popular to use them early on to control high blood sugar.

Many patients believe that because this new class of agents must be injected, that they are like insulin and, therefore, should only be used as last-resort drugs with a high likelihood of side effects. However, these new agents are easy to use, much easier than insulin which has to be adjusted based on blood sugar levels, meal content and exercise and do not cause weight gain and hypoglycemia. Endocrinologists often start incretins when just metformin, which is considered a first-line drug to control type 2 diabetes, is not able to control blood sugars adequately. The addition of a once-daily or once weekly administration of a small subcutaneous injection appeals to many patients, since it can be taken without changing their mealtimes, meal content and exercise.

Research

Research is currently underway to see if incretins can help the heart. Studies in animals have shown that incretins can protect against the development of heart failure (when heart muscle does not pump blood normally and fluid accumulates throughout the body) and protect against the loss of heart muscle function after heart attack. Of course, animals and humans differ, so studies that show a very positive effect in animals might not show the same effect in humans. So far though, physicians have learned that after taking incretins for a while blood pressure goes down and cholesterol levels drop, which fits with what we know about research in animals. Stay tuned!

Characteristics of Injectable Incretin Drugs
Agent Exenatide Liraglutide daily Exenatide weekly
Trade Name Byetta Victoza Bydureon
Frequency of dose Twice daily Once daily Once weekly
A1c Reduction Mild Moderate Moderate
Weight loss 4-7 lbs. 6-9 lbs. 4-7 lbs.
Side effects Nausea Occasional vomiting (Usually subsides in several weeks) Nausea Occasional vomiting (Usually subsides in several weeks) Nausea Rare vomiting (Usually subsides in several weeks)
Frequently used with Metformin Pioglitazone Once daily insulin Metformin Pioglitazone Once daily insulin Metformin Pioglitazone Sulfonylureas
Dosing Before meals Once weekly at any time Once a week

Dr. Alan Garber graduated from Temple University, Philadelphia, completed a PhD in chemistry and a residency in internal medicine, Subsequently, he was a fellow in metabolism and then a junior faculty member at Washington University Medical School and Barnes Hospital in St. Louis. He transferred to Baylor College of Medicine, where he was an investigator for the Hoiward Hughes Medical Institute and is presently a Professor in the Departments of Medicine, Biochemistry and Molecular Biology, and Molecular and Cellular Biology. Dr. Garber currently serves as president of the American Association of Clinical Endocrinologists (AACE).