There's a new diabetes drug currently before regulators that, if approved, would be the first oral medication designed to be used alongside insulin for people with type 1.

Created by Sanofi and Lexicon Pharmaceuticals, this new drug called Zynquista (scientific name "Sotagliflozin") is under review by FDA. If approved, it will be the first-ever pill or tablet officially labeled for use by people with T1D alongside insulin to help keep blood sugars down -- and only the second-ever medication (after Symlin injections in 2005) to be approved to work in conjunction with insulin for T1Ds. WOW.

 

Peeing Out Excess Glucose

Zynquista will be taken orally and works to lower glucose levels by causing you to pee out excess glucose in the body. These "pee out glucose" meds already exist as SGLT-2s (Invokana, Jardiance, Farxiga, and Steglatro), but they're only FDA-cleared for use by those with type 2 diabetes. None are currently OK'd for T1D, even though some PWDs (people with diabetes) do use them off-label along with their insulin.

As a result of those "off-label" uses of other meds, Sanofi and Lexicon pushed for larger studies on Zynquista for use in T1D. Clinical data from 2017 and 2018 assessed the safety and efficacy of Zynquista, involving approximately 3,000 adults with "inadequately controlled type 1 diabetes." It showed that Zynquista, along with insulin therapy, offered sustained A1C reduction, weight loss, better blood pressure, lower insulin doses, fewer severe hypos, and generally improved Patient Reported Outcomes (quality of life measures).

This past March, the FDA accepted the new drug application by Sanofi and Lexicon and set a potential regulatory review time for March 22, 2019. The companies have also filed this with European regulators.

In a statement at that time, Lexicon's Executive VP and Chief Medical Officer Dr. Pablo Lapuerta emphasized the need for progress in T1D medications: "After decades of little change and innovation, the treatment of type 1 diabetes has begun to shift significantly and, if approved, our dual SGLT-1 and SGLT-2 inhibitor, Zynquista, would be the first approved oral therapy used in combination with insulin to improve glycemic control and patient outcomes for adults in the United States who are living with type 1 diabetes."

The JDRF has also praised Zynquista, noting the clinical studies it's been involved with on the funding side.

 

Zynquista Medication Pros and Cons

Our friends Drs. Steve Edelman and Jeremy Pettus of Taking Control Of Your Diabetes (TCOYD) in San Diego, who were involved in the studies, are more familiar with Zynquista than probably anyone outside the manufacturers at this time. They kindly agreed to share their (slightly snarky) list of Pros and Con with us and our readers here at the 'Mine:

Dr. Jeremy Pettus and Dr. Steve Edelman

 

Zynquista Benefits:

1. CGM data consistently shows fewer highs and fewer lows improving time in range (70 to 180mg/dL) and reduced variability. In one study with the higher dose, the volunteers spent three more hours a day in range. Peeps who were in the study say their ups and downs were dampened, and dosing insulin was more predictable in terms of their glucose levels throughout the day and night.

2. Less mild and severe (defined as doing the fried egg and needing glucagon) hypoglycemic reactions compared to the insulin-only treated group. This lower incidence of hypos occurred in the face of lower insulin doses, mainly in bolus dosing.

3. Reduction in body weight of ~3 to 4% . For example, if you weighted 180 pounds you would have lost about 5 to 7 lbs. It turns out that us type 1s are getting heavier as we get older (we hate data like this!)

4. Reduction in A1C of about 0.3 to 0.4% from a baseline of about 7.5 to 7.8%. This does not sound like much but the CGM data is more meaningful to us. This is why it is number 4.

5. Reductions in blood pressure… every little bit helps!

6. Improves male pattern baldness and erectile dysfunction… just kidding.

 

Zynquista Downsides:

1. Genital yeast infections mainly in women and uncircumcised men due to the higher glucose levels in the urine. The rates were low, easily treated and did not lead to folks dropping out of the study. 

2. Risk of DKA or diabetic ketoacidosis, that may go unnoticed (!) DKA can be serious and lead to emergency room visits and hospitalizations, and it's a major concern with this and all of the other drugs in the same class (SGLT inhibitors). A study last year indicated that the risk of DKA is doubled in people taking SGLT-2 drugs.

In some cases, DKA occurred when the glucose values where not that high (less than 250mg/dL), with some evidence that this class of SGLT drugs may "mask" DKA so that the PWD and even their doctor don't identify it until the patient is in real danger. In other words, one could be fooled and not realize they are developing until it's too late and they need to go to the ER, usually with nausea and vomiting. 

All that said, the rate of DKA in Zynquista studies so far was very low (3 to 4% of research participants compared to 1% in the insulin-only placebo group, over one year of treatment),

 

Dr. Pettus adds: "Risk mitigation strategies are being worked out focusing on education. Other measures may include having access to a meter that measures ketones, so you can test at home periodically (especially when not feeling well). When they looked at all of the peeps with T1D who developed DKA, they noticed a lot of them had common features like high A1Cs, those that missed their insulin doses regularly, and pumpers who disconnected for long periods of time or had infusion line malfunctions. Treatment is insulin, fluids and carbohydrates. Yes, I said carbohydrates, which help to limit ketones in the blood."

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UPDATE 3/24/19: Despite the companies' risk mitigation efforts, the FDA has initially rejected Zynquista as an add-on treatment for T1Ds using insulin. This agency decision followed a divided panel vote in January 2019, where members cast a split 8-8 vote on recommending Zynquista for approval. Now, Sanofi and Lexicon have said they plan to work with regulators in determining the next step.