Saturday, November 12, 2011

The GLP-1 Agonists: Which Is the Winner?

With the FDA approval of Bydureon in January 2012, there will be three injectable GLP-1 agonists available for the treatment of Type 2 Diabetes.

The battle of the GLP-1's will shortly be in full swing.

Each of the injectable GLP-1 agonists (Byetta, Victoza and Bydureon) are incretin-based therapies.

Incretins are hormones that are released by the gut in response to a sugar load from a meal.

Once released, the incretins stimulate insulin secretion, reduce glucagon secretion, and slow the transit of food in your gut.

Together, these actions lower your fasting and after-meal sugars.

The GLP-1 agonists also reduce appetite, resulting in weight loss.

Despite similar modes of action, each GLP-1 has it's own advantages and disadvantages.

I've summarized 7 clinically significant differences between Byetta, Victoza, and Bydureon.

I haven't included cost (since it is unknown where Bydureon will be placed on different formularies), potential cardiac benefits (since the clinical signficance of these differences isn't known), or the potential increased risk for pancreatitis or a rare form of thyroid cancer (due to the lack of definitive studies) in this review.

See if you think there is a winner.

Method of administration

Byetta and Victoza are available in simple to use pens.

Bydureon will initially be available as a vial only, and will require that you mix a solution and powder (reconstitution) to use the medication.

Reconstitution must occur at the time of injection.

The process of reconstitution, as well as the need for reconstitution-related supplies, and requirement for preparation only at the time of use, may be a stumbling block for some.

Advantage: Byetta and Victoza

Frequency of administration

Byetta is typically administered twice daily, within 60 minutes of a meal.

Vicotza is administered once daily, without regard to meal time.

Bydureon is administered once weekly.

Advantage: Bydureon

Dosing complexity

Byetta has two dosing options: 5 mcg and10 mcg.

Administration typically begins with a one-month course of twice daily 5 mcg, followed by an increase to 10 mcg twice daily as tolerated.

Victoza has three dosing options: 0.6 mg/day, 1.2 mg/day, and 1.8 mg/day.

The typical starting dose of 0.6 mg is increased to 1.2 mg daily after 1 week.

The 1.8 mg/d dose is used infrequently.

Bydureon is available in only one dose, 2 mg/week.

Dose adjustment is not required with Bydureon.

Advantage: Bydureon

Efficacy

Although each of the GLP-1 agonists will reduce HA1c levels an average of 1-1.5%, clinical trials suggest that Victoza is slightly more effective at glucose and HA1c reduction than the other agonists.

Victoza is associated with an average additional A1c reduction of 0.3% compared with Byetta and an additional 0.2% compared with Bydureon.

Advantage: Victoza

Glucose pattern

Byetta is a short-acting GLP-1 agonist. As such, it is most effective at reducing after meal sugars.

Victoza and Bydureon are long-acting GLP-1 agonists. Their greatest impact is on AM fasting sugars.

Advantage: Tie. Depends on the pattern of your sugar elevations

Weight loss

The GLP-1 agonists are associated with an average weight loss of ~5-8 pounds after 6 months of use. People treated with the GLP-1's describe a sensation of "fullness" which occurs earlier than usual during a meal. This is believed to be mediated by an effect of the medications on the brain hunger center.

Victoza had been associated with an additional weight loss of 2 pounds when compared to Byetta and Bydureon.

A sub-population of patients treated with Byetta note a significant reduction in the drug's ability to reduce appetite after 1 year.

Advantage: Victoza

Nausea

Gastrointestinal problems, such as nausea, are one of the most common side effects of the GLP-1 agonists.

The nausea is typically self-limited, and dose related.

Byetta has the greatest reported frequency of nausea.

Bydureon has the lowest frequency of nausea.

Advatage: Bydureon

Final tally: 1 win for Byetta, 3 wins for Victoza, 3 wins for Bydureon, and one tie.

There isn't a definitive winner, but clearly the battle currently appears to be beween Victoza and Bydureon.

Your medication choice will depend on which characteristics are most important to you.

If frequency of dosing is a deciding factor, Bydureon is the winner.

If efficacy is more important, Victoza is the winner.

My current personal preference is Victoza.

It's advantages include once daily dosing and superior efficacy for sugar reduction and weight loss.

Bydureon will become a more attractive option once it is available as a pen.

Outcome data in heart studies, as well as more information regarding potential risks such as pancreatitis, may also influence medication choices once they become available.

This is only a brief overview of the GLP-1 agonists.

Continue to read and learn about these drugs so you can participate with your physician in making an informed decision about which medication is best for you.

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