SGLT2 Inhibitors in Type 1 Diabetes – Where Do We Stand in 2025?
SGLT2 inhibitors have dramatically advanced the management of type 2 diabetes by reducing glycemia, cardiovascular events, and renal disease progression. Their use in type 1 diabetes (T1D) remains off-label, with diabetic ketoacidosis (DKA) as the main safety concern. Nonetheless, data continue to emerge around potential glycemic, weight, and renal benefits, especially in individuals with early diabetic kidney disease (DKD).
What the Evidence Shows – Glycemic and Metabolic Effects:
Trials like DEPICT-1 & 2 (dapagliflozin) and inTandem 1–3 (sotagliflozin) demonstrated:
HbA1c reduction (~0.3–0.4%)
6–15% insulin dose reduction
2–3 kg weight loss
Reduced glycemic variability
However, these came with 3–4x higher DKA risk, particularly in pump users or those with insulin dose reductions >20%.
What About Kidney Protection?
Although not powered for renal endpoints, subgroup and post hoc analyses show promising signals:
DEPICT pooled analysis: Dapagliflozin slowed albuminuria progression and preserved eGFR.
Real-world studies: Small observational cohorts have noted stabilization of renal function in patients with T1D and microalbuminuria.
Mechanisms: Renoprotective mechanisms—like reduced intraglomerular pressure and improved tubuloglomerular feedback—are likely operative in T1D, though definitive evidence is lacking.
Upcoming: The SUGARNSALT trial, a multi-center double-blinded, randomized controlled trial evaluating the renal benefit of sotagliflozin on patients with Type 1 diabetes anticipated at the end of 2028; this will incorporate a DKA prevention program to limit the risk of diabetic ketoacidosis.
Future Safety Innovation: Continuous Ketone Monitoring (CKM)
A key limitation to wider use of SGLT2 inhibitors in T1D is the difficulty in detecting early euglycemic DKA. Enter continuous ketone monitoring:
What is CKM? Continuous ketone monitors (CKMs) measure interstitial β-hydroxybutyrate in real time. Like CGMs, they offer trend data and alerts for rising ketones—crucial for SGLT2 safety.
So far, pilot studies (e.g., Abbott and other industry-sponsored trials) have demonstrated reliable ketone detection trends and improved patient behavior (e.g., earlier insulin corrections, SGLT2 discontinuation when needed). There are no large-scale RCTs yet, but algorithm-driven alerts combined with patient education show promise.
When Will CKMs Be Available? Abbott and other developers anticipate FDA clearance by late 2025 or early 2026. Integration with CGM + insulin delivery systems may evolve next.
Regulatory Status & Practical Use of SGLT2 Inhibitors
FDA & ADA: SGLT2 inhibitors remain not approved for T1D.
Use in patients with T1D and DKD remains experimental, though many endocrinologists consider it in:
Overweight or insulin-resistant individuals
Microalbuminuria with preserved eGFR
High cardiovascular risk
Clinical Decision-Making when considering SGLT2 inhibitors Off-Label
Use the lowest available dose (e.g., dapagliflozin 5 mg)
Educate patients on ketone testing and sick day rules
Consider real-time or daily ketone monitoring
Discontinue during illness, surgery, or fasting
Avoid in underweight patients, restrictive eaters, or those with history of DKA
Bottom Line about SGLT2 inhibitors in Type 1 Diabetes
SGLT2 inhibitors may offer meaningful glycemic and renal benefits for highly selected patients with T1D and early DKD. However, DKA risk remains the limiting factor. The advent of continuous ketone monitoring by 2025–2026 could be a game-changer—paving the way for safer implementation in this population. Additionally, prospective studies are being conducted at this time as well
Until then, SGLT2 use in T1D should remain specialist-guided, patient-specific, and tightly monitored.
