According to the American Diabetes Association, the most effective 20% of patients with type 1 diabetes hold the encouraging A1C target of <7%. The only noninsulin adjunctive therapy for type 1 diabetes is pramlintide, and it is rarely utilized due to unwanted side effects and limited efficacy. Intensive insulin regimens are the only effective FDA approved treatment for type 1 diabetes and have unwanted side effects such as hypoglycemia and weight gain.
SGLT2 inhibitors block the SGLT2 transporter resulting in glycosuria and natriuresis, and SGLT1+2 inhibitors have the added benefit of delaying the absorption of glucose and galactose. SGLT inhibitors have already proven to be safe and effective in the treatment of type 2 diabetes, reducing the risk of hypoglycemia, and simultaneously protecting the kidneys and heart. This has led to the investigation of SGLT inhibitors in type 1 diabetes, but recent study results raise serious concerns.
DKA was an event of special interest in the recent FDA drug application review for sotagliflozin, an SGLT inhibitor for use in type 1 diabetes. In this study, participants were excluded from recent DKA or ketosis. Due to the DKA concern, participants received extensive education, a ketone meter with strips, and instructions on detecting and managing ketosis. Despite this protocol, sotagliflozin SGLT inhibitor therapy increased the relative risk of DKA between 5 and 17-fold with a number needed to harm from between 21 and 31. Alternatively, the placebo group had a low incidence of DKA.
A recent international consensus on SGLT inhibitors in type 1 diabetes was released to address the risk of DKA. These recommendations were based on clinical trials and experts who used SGLT inhibitors with their type 1 diabetes patients. This consensus indicates that providers should perform a thorough risk assessment prior to initiating SGLT inhibitor therapy in type 1 diabetes.
Appropriate selection of patients for this therapy is paramount to reduce DKA risk. This criterion includes normal ketone levels, the willingness and ability to follow a prescribed regimen to monitor ketones, access to health resources for proper monitoring, and the financial ability to purchase ketone monitoring supplies. Conversely, SGLT inhibitor therapy is not recommended in patients: on low carb diets, who skip meals, consume excessive alcohol, have recurrent DKA, or prolonged hyperglycemia (>350 mg/dL). Although not surely contraindicated, patients on an insulin pump want to take extra precautions because of an elevated chance of headaches.
The populace of sufferers with kind 1 diabetes who might most benefit from an SGLT inhibitor additionally carries the very best danger of DKA. Patients who have low involvement in their diabetic routine are much less in all likelihood to stick to complicated safety suggestions required for this drug therapy. For example, teenagers with an AIC >9% could substantially benefit from additional glucose manage with upload on remedy, but are at increased risk of DKA, and are not an excellent candidate for therapy. Lifestyle selections, ailment management, and conduct are at once connected to effects and drug remedy threats.
A principal paradigm shift is vital for each sufferer and providers to mitigate the danger of DKA. We ought to alternate from “glucose centric” to “ketone centric” to securely put in force SGLT inhibitor therapy in kind 1 diabetes. Euglycemic DKA, generally visible in this therapy, can’t be detected by glucose monitoring and requires ketone tracking. In euglycemic DKA, sufferers can gift with a blood glucose of <250 mg/dL and be in complete-blown DKA. This scenario complicates the popularity and analysis of DKA and can delay remedy. The worldwide consensus recommends a diligent assessment of ketones within the presence of any DKA signs to reduce this risk.
Additional research is needed to evaluate the efficacy and DKA threat of SGLT inhibitors in type 1 diabetes. The secure use of SGLT inhibitors in kind 1 diabetes does appear viable in sufferers who meet a hard and fast criterion, however, due to the growth in absolute risk of DKA, carriers need to proceed with warning.
The advantages of SGLT inhibitors in kind 1 diabetes are clinically significant, however, the drugs must be used with warning, and only by the ones who have the sources and schooling to carefully pick patients.
The top-rated DKA hazard mitigation approach includes clinician schooling, patient education, and hazard conversation.
Even in the closely supervised FDA drug trial of sotagliflozin, there was a boom in the absolute hazard of DKA.