Add on Empagliflozin to automated insulin delivery improves glycemic control in type 1 diabetes

USA: A new study showed that the use of empagliflozin as an adjunct to automated insulin delivery (AID) improved glycemic management in adults with type 1 diabetes (T1D) without increased hypoglycemia risk. The study data was published in Diabetes Technology & Therapeutics.

Type 1 diabetes (T1D) is a disease of multiple hormonal and metabolic impairments. Overall, T1D affects nearly 20 million individuals worldwide. In addition to deficient insulin secretion from the pancreas, patients experience insulin resistance, increased cardiovascular disease risk, increased glucose reabsorption by the kidneys, and other abnormalities that are not directly addressed by current treatments. Medications that can be used alongside insulin to simultaneously improve glycemic control and target other metabolic abnormalities are needed.

Empagliflozin, a sodium-glucose co-transporter-2 (SGLT2) inhibitor is an FDA-approved, newer class of agents that act in an insulin-independent manner to improve glucose control while demonstrating significant cardio-renal benefits in type 2 diabetes. Their use as adjuvant therapy to insulin in T1D, however, has been controversial.

Automated insulin delivery (AID) systems are now commercially available and have improved the management of glycemia in people with T1D. These systems have performed better than traditional insulin replacement strategies concerning a greater percentage of glucose time-in-range (TIR), lower time in hypoglycemia, and reduced glucose variability. Most AID systems consistently improve overnight control, but previous studies have shown their limitations in achieving optimal daytime control.

Garcia-Tirado J, University of Virginia, USA, and colleagues conducted a proof-of-concept, safety, and feasibility study to assess whether daytime glycemic control using a commercially available hybrid AID Control-IQ™ (CIQ) system or predictive low glucose suspend (PLGS) Basal-IQ™ (BIQ) system can be improved by a low-dose (5 mg/day) empagliflozin adjuvant therapy.

Researchers enrolled a total of 39 adults with T1D for an 8-week outpatient clinical trial. Patients were randomized to receive 5 mg/day of empagliflozin (EMPA) or no drug (NOEMPA) as an adjunct to insulin therapy. Analysis was done according to the intention-to-treat principle. Participants were also randomized to sequential orders of AID (Control-IQ) and PLGS (Basal-IQ) systems for 4 and 2 weeks, respectively. The primary endpoint was percent time-in-range (TIR) 70–180 mg/dL during daytime (7:00–23:00 h) while on AID.

Key findings of the study,

• On AID, EMPA versus NOEMPA had higher daytime TIR 81% versus 71% with a mean estimated difference of +9.9%. 

• On PLGS, the EMPA versus NOEMPA daytime TIR was 80% versus 63%, mean estimated difference of +16.5%. 

• One subject on SGLT2i and AID had one episode of diabetic ketoacidosis with non-functioning insulin pump infusion site occlusion contributory.

The authors conclude that an addition of 5 mg daily empagliflozin to AID or PLGS systems significantly improved daytime glucose control in individuals with T1D, without increased hypoglycemia risk. However, the risk of ketosis and ketoacidosis is still a concern. Therefore, future studies with SGLT2i may need modifications to closed-loop control algorithms to enhance safety.

Reference:

 Garcia-Tirado J, Farhy L, Nass R, Kollar L, Clancy-Oliveri M, Basu R, Kovatchev B, Basu A. Automated Insulin Delivery with SGLT2i Combination Therapy in Type 1 Diabetes. Diabetes Technol Ther. 2022 Jul;24(7):461-470. doi: 10.1089/dia.2021.0542. Epub 2022 Mar 14. PMID: 35255229.