Byetta, Victoza, Bydureon and the DPP-4's

    Byetta, Victoza, Bydureon and the DPP-4's (Januvia, Onglyza and Tradjenta) are medications which are related to the Incretins.

    Incretins are hormones that are released in the gut in response to a meal. 

    The incretins promote insulin secretion, inhibit glucagon, and slow emptying of the stomach. The result of these effects is to lower sugar levels in the morning and after eating a meal. 

    Incretins also appear to promote the growth and survival of beta cells (the cells that release insulin). It is unknown if this is clinically relevant in humans.

    The insulin-secreting effects of the incretins depend on blood sugar levels. They have their greatest effects at high sugar levels, when increased insulin secretion is needed.

    When sugar levels are normal, they have minimal effects, thus avoiding hypoglycemia (low sugar).

    Although these benefits were first noted over 50 years ago, incretins were not previously available as therapy since the hormones lasted less than 10 minutes in your circulation. 

    Researchers however recently identified technologies that allowed the incretins to last for longer periods of time. 

    This allowed physicians to use the incretins to treat people with Type 2 Diabetes, in whom incretin related actions are typically reduced.

    The first class of incretin related drugs developed were the "incretin mimetics". 

    Byetta and Victoza were the first drugs available in this class. Bydureon was introduced in 2012. All are delivered by injection.

    Byetta is a synthetic formulation of exendin 4, a hormone found in the Gila monster. It is very similar to the human incretin (53% homology), but much more resistant to breakdown. It thus lasts for more than 2 hours (compared to 10 minutes!).

    The initial formulation of Byetta requires two injections per day. 

    Bydureon is an extended release form of Byetta. It is injected once weekly.

    Although Byetta and Victoza are available in easy to use pens, Bydureon is currently available as a vial only.

    It requires mixing ("reconstitution") immediately prior to use.

    Several other incretin mimetics, such as lixisenatide, are currently being studied in clincal trials.

    Given its relatively short duration of action, and twice daily meal-time dosing, the short-acting formulation of Byetta is most effective at lowering after-meal blood sugars.

    Victoza has been chemically modified to resist breakdown. It lasts for 11-13 hours, and is injected once per day. 

    Given its longer duration of action, Victoza is most effective at lowering morning sugars.

    Bydureon's effect is likewise greatest for morning sugars.

    On average, all will reduce HA1C levels by 1-2%, lower after meal sugars by ~50 mg/dl, and lower fasting sugars by ~25 mg/dl.

    All  are associated with reduced appetite and an average weight loss of 6 pounds after 6 months. At one year, the average weight loss is 10 pounds.

    Victoza appears to be slightly superior to Byetta with respect to glucose lowering efficacy and weight loss.

    The weight-loss benefits associated with this class of drugs are typically described as an early sense of "fullness" while eating a meal.

    The drugs have also been associated with small reductions in blood pressure.

    New retrospective data suggests a potential role for incretins in the reduction of heart-related risk. 

    Prospective, placebo-controlled clinical trials regarding heart disease reduction are now underway at our research center.

    Incretin related side effects include nausea, and rarely, vomiting. 

    Gastrointestinal complaints are typically dose-related, and lessen with time.

    Bydureon has the lowest rate of stomach upset. Byetta the highest.

    Recently, cases of acute pancreatitis have been described in people treated with Byetta and Victoza. A causal relationship has not been definitively identified. 

    Risk assessment is complicated since pancreatitis risk is already increased in people who are obese and who have Type 2 Diabetes.

    Thyroid tumors were seen in mice and rats treated with Victoza in pre-clinical trials. 

    These findings were not observed in monkeys. There were no reported cases of medullary thyroid cancer in human clinical trials.

    The second class of incretin related drugs are the "DPP-4 inhibitors". 

    The DPP-4 inhibitors (also known as the DPP-4's) inhibit the breakdown of the incretins, thereby increasing circulating levels of these hormones. 

    Currently available drugs in this class include Januvia, Onglyza and Tradjenta. All are once daily oral medications.

    The DPP-4 inhibitors reduce HA1C levels by 0.8% on average.

    Fasting and after-meal blood sugar levels are also reduced. They 
    are "weight-neutral" without an effect on appetite.

    Their glucose lowering effects are less than the injectable drugs reviewed above.

    The DPP-4 inhibitors are very well tolerated due to simple once daily dosing and rare side effects.

    Tradjenta does not require dose alteration in the setting of kidney disease.

    There is an increasing amount of data suggesting an association of positive heart benefits with the DPP-4's.

    Clinical trials are underway at our center to study this.

    We have several ongoing trials studying the injectable and oral drugs in this class at our research center.

    If interested in more information, please contact our study coordinator at 301-770-7373.

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