Follow up on SGLT2 use for Type 1 Diabetes: FDA refusal maintains a troubling trend of delaying Type 1 treatment options.
It’s been about 6 months since we posted about the off label use of SGLT 2/SGLT 1 medications in coordination with insulin therapy. There has been a lot of talk about this area as Sanofi submitted their SGLT2 medication, Zynquista (sotagliflozin) for FDA review.
However in late March the FDA replied to Sanofi with a denial. This “complete response letter” has not been released so exact details on the reason for the refusal to approve are not available. However it is pretty easy to guess that the hold up centers around DKA risk. As we discussed in our October Newsletter article: SGLT2 use in type 1 diabetes benefits and risks.
SGLT2 use in patients also using insulin has been shown to increase DKA risk. This risk caused a split vote in the FDA advisory committee (per attendees of the advisory board testimony the vote was comprised of 8 diabetes specialists voting for approval , and 8 non specialists voting opposed.) It is likely that the FDA will require Zynquista to provide expanded studies and an action plan on reducing DKA risk through expanded patient and clinician education or monitoring. This has already been a big hit to the financial side as Sanofi and partner Lexicon pharmaceuticals saw a large drop in stock value after the announcement went public. We certainly hope that this is not the end of the road for Zynquista and other medications being approved for the Type 1 population, but the delay is certainly not encouraging for investors and other companies to jump into the pool!
Meanwhile, across the pond…
Barely more than a week after the FDA denied approval for use in an SGLT2/1 medication for people with type 1 diabetes, the European Medicines Agency approved use for the Astra-Zeneca produced medication of the same class Forxiga (Dapagliflozin, under the brand name Farxiga in the US). In the EU approval is restricted to patients with type 1 diabetes on insulin and a BMI of 27 or higher. Manufacturers also have to include a DKA action alert card with the medication as well as expanded education to clinicians. Approval is also conditional on results of ongoing studies of DKA risks and impacts of patients using the medication.
This is an unfortunately common picture. Medications and technologies typically receive approval in the EU months or even years ahead of US FDA approval. In a nation where the costs of diabetes care are sky rocketing and less than 25% of people with type 1are meeting A1C goals (T1D Exchange 2016-2018) , it is shocking that our regulatory agencies continue to delay in approving therapies and technologies that are showing benefit across the developed world. This delay causes investors to second guess funding development of adjunctive therapies for Type 1 management. And clearly insulin alone, in the current healthcare system is not enough to get most of us to our treatment goals. If current medications are not able to get approval for FDA approved user in Type 1 populations, what incentive is there for further research into new, innovative medication development?
We continue to recommend that patients who feel they need additional medication support to reach their goals discuss whether off label medication use would be beneficial for them. The lack of FDA approval does not mean that prescribers can not order these medications for patients, it typically just means that insurance companies are less likely to cover them and prior authorizations will be needed. We often need to be our own educators and advocates to make sure we have access to the treatments that will work best for us, even if it takes years for the FDA to finally approve what we’ve been doing all along. (you know, like alternate sites for CGM wear and using the data to replace finger sticks) We also encourage people with Type 1 to lend their voice to national and state level efforts to increase approvals and accessibility. Meanwhile we will continue to educate our community and our patients on all of the options and continuing developments.
According to the recent study Sodium-Glucose Cotransporter-2 Inhibitors (SGLT2) are linked to a dangerous genital infection known as “Fournier gangrene.” SGLT2 is found in Type 2 medications. This shows that the Type II Diabetes patients are at more risk of getting their genital infected by Fournier gangrene.
Check out the report- https://www.myhealthyclick.com/type-ii-diabetes-drugs-may-cause-infection-that-destroys-genitals-warns-study/
This is an exacerbation in an already rare side effect. People with diabetes are already at increased risk for this infection due to carrying increased glucose in our urine. This is an example of why patient education on medication risks and symptoms to be aware of and report are important. But this is a very small risk to negate the potential benefit of the medication when compared to the risks associated with chronic hyperglycemia. Individual risk benefit analysis is always critical to initiating any therapy.