Before the discovery of insulin in the early 1920s, our brethren who came down with type 1 did not live too long and passed from either starvation, which was the only form of therapy at the time, or diabetic ketoacidosis because of a state of severe insulin deficiency. Having insulin was literally a life saver…BUT…all of us living with type 1 would say we could use something else to work with insulin to help with the unpredictable highs and lows that we have to deal with day in and day out (unless you have a closed loop fully functioning artificial pancreas, you SOB!).
It has been nearly 100 years since the discovery of insulin and we have had only ONE other medication approved for type 1 diabetes. Amylin is a sister hormone to insulin that is co-released when the glucose levels rise and helps to limit the post meal rise. Symlin (amylin analog) was approved in 2005 but is rarely prescribed at the current time and did not live up to its potential (it’s a long story why). We bet many of you have never heard of it! Look it up in Urban Dictionary.
Sotagliflozin (brand name Zynquista) is an oral medication that works to prevent glucose reabsorption in the kidney and gut, leading to excretion of excess glucose into the urine. We call this POG or peeing out glucose. Believe it or not, we already have four similar medications approved for use in type 2 diabetes (Invokana, Jardiance, Farxiga, and Steglatro). Many folks with type 1 are using these medications “off label” and have discovered many advantages. So the makers of sotagliflozin (Sanofi and Lexicon) decided to do larger studies in type 1 diabetes and take their data to the FDA for the formal approval of its use in type 1 diabetes. Other companies are closely following them.
We think the upside is pretty darn good. Here are some of the benefits that were seen:
- CGM data consistently showed fewer highs and fewer lows, improving TIR or time in range (70 to 180mg/dl) and reduced variability. In one study with the higher dose of sotagliflozin, 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 predicable in terms of their glucose levels throughout the day and night.
- There were also 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.
- A reduction in body weight of ~3 to 4% . For example, if you weighed 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!
- A reduction in HgbA1c 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.
- Reductions in blood pressure…every little bit helps!
- Improved male pattern baldness and erectile dysfunction…just kidding.
Now the downsides:
- 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.
- The major concern with sotagliflozin and all of the other drugs in the same class (SGLT inhibitors) is DKA or diabetic ketoacidosis, which can be serious and lead to emergency room visits and hospitalizations. Most of us got DKA when we were first diagnosed or when our pump infusion line came out and we did not notice it. Some of us got DKA when we were really sick from the flu, for example, and under-dosed ourselves with insulin. The rate of DKA is very low (3 to 4% of research participants compared to 1% in the insulin-only placebo group, over one year of treatment).
One of the special concerns is that several of the cases of DKA occurred when the glucose values where not that high (less than 250mg/dl). You can google euglycemic DKA/SGLT inhibitors and read a ton on the topic. Most doctors and PWD associate DKA with extremely high glucose levels, so one could be fooled and not realize they are developing acidosis and discover it too late and need to go to the ER, usually with nausea and vomiting.
What’s being done:
Risk mitigation strategies are being worked out right now, and are focusing on education. Other measures may include having access to a meter that measures ketones (BHB or beta hydroxy butyrate…sorry you asked?) so you can test at home periodically and 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 who 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.
Well folks. There you have it. You now know more about sotagliflozin in type 1s than 99.9% of healthcare professionals. We will get back to you as we learn more about POG.