Possible Breakthrough for Type 2s: The First GLP-1 Pill Is Submitted for Approval to the FDA and EMA

By Emma Ryan and Ann Carracher

The first GLP-1 pill for type 2 diabetes offers weight loss and A1C reduction without injections; US decision expected in September 2019, EU decision expected spring of 2020

An oral (pill) version of Ozempic, a once-weekly , injectable GLP-1 agonist for adults with type 2 diabetes, was recently submitted to the European Medicines Agency (EMA) for approval. Oral Ozempic has also been submitted for approval in the US and Canada. If approved, oral Ozempic would be the first GLP-1 agonist pill.

Studies show that oral Ozempic is effective at lowering A1C and helping with weight loss. Clinical trials show:

• Compared to placebo (a “nothing” pill): Over six months, participants taking oral Ozempic saw an average A1C decrease of 0.9% – 1.4%, compared to a 0.3% decrease in the placebo group. They also lost an average of 3 – 8 pounds depending on the dose, compared to about 3 pounds of weight loss in the placebo group.
• Compared to Jardiance (once-daily SGLT-2 inhibitor pill): The highest dose of oral Ozempic (14 mg) lowered A1C more than Jardiance: 1.3% decrease vs. 0.8% decrease.  Average weight loss was about 10 pounds for oral Ozempic and 8 pounds for Jardiance.
• Compared to Januvia (once-daily DPP-4 inhibitor pill): The two highest doses of oral Ozempic lowered A1C by 1.1% – 1.4% and resulted in about 5 – 7 pounds of weight loss compared to 0.8% A1C decrease and 1.5 pounds lost with 100 mg of Januvia.
• Compared to Victoza (once-daily injectable GLP-1 agonist): The highest dose of oral Ozempic resulted in a 1.3% decrease in A1C and weight loss of about ten pounds. Those on Victoza saw a 1.1% decrease in A1C and weight loss of about seven pounds.

A decision in Europe is expected in Spring 2020. A US approval decision is expected by September 2019. Currently, GLP-1 agonists are only available as injections, ranging from twice-daily to once-weekly.

Though approval of oral Ozempic would mean that people could benefit from A1C-lowering and weight loss of GLP-1 agonists without injections, the pill could possibly be seen as less convenient for some people due to the once-daily pill dosing requirement compared to a once-weekly injection. We don’t see “switching” from injectable Ozempic to pill as likely as starting GLP-1 for the first time with a pill – and that might be because many people may have doctors who think they do not have time to teach an injection (which is far easier these days than it used to be).

In the trials assessing oral Ozempic, participants took the pills in the morning and waited 30 minutes before eating, drinking, or taking any other oral medication. Additionally, some people reported nausea as a side-effect – about the same percentage that reported nausea as a side effect with other GLP-1 agonist drugs. One study found that 5-16% of people taking Ozempic (depending on the dose) reported nausea, compared to 6% of those in the placebo group. From our view, that’s well over 80% for whom nausea should not be an issue; if it is not tolerable, of course, today there are other options, as long as healthcare providers have time to discuss it.

Evidence suggests that both oral and injectable Ozempic can be very beneficial for heart health: reducing risk for heart attack, stroke, and heart-related death. This is an important benefit given that people with type 2 diabetes are at a higher risk of heart disease. Victoza (another GLP-1 agonist), along with Jardiance and Invokana (both SGLT-2 inhibitors) are already approved to reduce the risk of heart problems.

Data recently presented at American Diabetes Association (ADA) Scientific Sessions suggested that oral Ozempic is safe for the heart and supports A1C reduction and weight loss. In a population of people with type 2 diabetes and heart disease or had risk factors for heart disease, compared to placebo, oral Ozempic:

• Reduced risk of heart-related death by 51%;

• Did not have a meaningful difference in heart attacks;

• Did not have a meaningful difference in strokes;

• Reduced A1C by 1.0% from a starting A1C of 8.2%; and

• Reduced weight by about 9 lbs (4.2 kg) from a starting weight of 200 lbs (91 kg) – this is nearly 5% of body weight lost, which is very meaningful.

It is unclear if oral Ozempic will be priced similarly to injectable Ozempic – we hope it will be as accessible as possible so that many people can access GLP-1 agonists when it will be beneficial – often early after diagnosis of type 2, if they are at risk of heart disease.