When your doctor says it’s time to add another diabetes medication, you will have some questions. When they suggest a Glucagon-Like-Peptide or GLP-1 agonist (Trulicity, Ozempic, Victoza, etc.), you’ll want to know some details on this newer class of drugs before buying in. GLP-1’s aren’t oral meds, but they clearly are not insulin either. GLP-1 agonists are delivered through injectable pen devices that can be used daily or weekly, depending on which drug is prescribed. This class has some distinct advantages and is becoming more commonly used in the diabetes medication tool chest.
GLP-1 Agonist Drugs
- Dulaglutide (Trulicity)
- Exenatide (Byetta)
- Exenatide Ext Rel (Bydureon)
- Liraglutide (Victoza)
- Lixisenatide (Adlyxin)
- Semaglutide (Ozempic)
How the GLP-1 agonists work
GLP-1 is a hormone which is released from the intestines after eating. The function of GLP-1 is to boost insulin secretion from the pancreas, reduce the amount of glucose that is released from the liver, and slow the rate that food leaves the stomach. The effect of all of these actions is decreased blood glucose (BG) levels, especially after meals. Drugs that are agonists work by enhancing or mimicking the effect of a hormone or neurotransmitter. So in this case, the action of insulin is enhanced.
As a result of these actions, many people lower their A1C 1-1.5% with these drugs. Some see even greater reduction.
Benefits of GLP-1 drugs
Besides the obvious lowering of BG (A1C decrease ranges from 1% to 1.5%), these drugs contribute to meaningful weight loss. Because of the action of food not leaving the stomach so quickly, people tend to eat less overall. A suppressed appetite is the result. Patients in studies experienced weight loss ranging from 4 -10 pounds over the year-long duration. More significant amounts of weight loss can be seen, but it varies with the level of changes in eating and activity that are implemented. Interesting fact: one of the drugs Liraglutide (Victoza) is sold under a different brand name (Saxenda) for weight loss in people who don’t have diabetes.
Cardiovascular safety and benefit of diabetes medications is now required by the FDA to become approved. Some of the GLP-1 agonists are known to be heart-protective while the features of others are unknown. Liraglutide (Victoza) and Semaglutide (Ozempic) are known to reduce heart disease-related deaths in people with diabetes. Exentatide (Byetta) and Lixisenatide (Adlyxin) were found to have a neutral effect (no harm/no benefit). Research looking at the heart protection of dulaglitide (Trulicity) is still ongoing.
Side effects of GLP-1 agonists
Common side effects
Because of the effects of appetite suppression, nausea, vomiting, and diarrhea are common in the first couple of weeks. To help relieve the stomach symptoms, eat smaller, more frequent meals, avoid fried or fatty foods, and stop eating when you are approaching full. Ginger tea may also help reduce nausea. For the weekly doses, taking it at bedtime often helps.
GLP-1 agonists don’t usually cause hypoglycemia on their own, but watch for this when combined with insulin or sulfonylureas (glipizide, glyburide).
Rare side effects
All of the drugs in this class have warnings about rare but serious side effects. Some of these are an inflamed pancreas (pancreatitis), making poorly functioning kidneys worse, and causing a certain type of thyroid C-cell tumors in animal studies. Each of the drugs has instructions for alerting your doctor if any symptoms of the serious side effects appear.
Dosing, Storage and Use
Because these are not simple oral pills, each of the drug manufacturers has either a video or detailed instructions for use on their respective website.
Most of the drugs have a low starting dose that is used initially, then can be increased after a few weeks or a month if side effects are not a problem. Some are sold with pen needles (same as used with insulin pens) while others are not. Check out this article for advice on purchasing pen needles.
Each of the pens should be stored in the refrigerator until the first use, then they can be kept at room temperature after that. Some of the drugs dosed once weekly are packaged as single-use disposable pens (Trulicity, Bydureon), but other pens with daily use last all month (Byetta, Victoza, Adlyxin). This chart compares the available drugs and key features.
Cost of GLP-1 agonists
One of the biggest disadvantages of the GLP-1 agonists is the high cost. None of the drugs are available as generics yet, making the cash prices quite high. They are usually the highest tier co-pay on most insurance plans, but many of the drug manufacturer websites have co-pay coupons or patient assistance programs that help.
Pros and Cons of GLP-1 agonists
No one likes to take an injectable drug, and these are not simple oral pills. The first week or two of nausea and stomach upset can be challenging, and the cost is high. The risk of more serious side effects is low, but may be concerning if you are already at risk for one of the complications (e.g. history of pancreatitis).
There aren’t many diabetes drugs that cause weight loss, and these are at the top of that short list. They can be taken along with insulin and will offset some of the weight gain that is normally seen with insulin alone. One of the drugs, liraglutide (Victoza) is approved at a higher dose as a weight loss drug (Saxenda) for non-diabetics. The risk of hypoglycemia is low. Any measure to lower the risk of heart disease in diabetes is a benefit.
Metformin is still the most commonly recommended first-line medication for diabetes, but GLP-1 agonists are becoming more frequently added as a second step medication.
If you’d like a comprehensive chart of all classes of diabetes medications, find one in our resource library.
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