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Triple therapy improves glycemia in type 1 diabetes

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BOSTON – The combination of insulin, a GLP-1 receptor agonist and an SGLT-2 inhibitor significantly improved glycemia in patients with type 1 diabetes, according to late-breaking data presented at the American Diabetes Association’s 75th Scientific Sessions.

However, researchers warned of a possible risk for diabetic ketoacidosis.

Nitesh D. Kuhadiya , MD, MPH, of the State University of New York at Buffalo, and colleagues, conducted a retrospective analysis of 10 patients on continuous glucose monitoring treated with insulin, Victoza (liraglutide, Novo Nordisk) and Farxiga (dapagliflozin, AstraZeneca). At baseline, patients had been receiving liraglutide added to insulin therapy for 11 months (mean HbA1c, 8%; mean age, 56 years; mean age of diabetes diagnosis, 29 years; mean BMI: 29 kg/m²). Dapagliflozin 5 mg daily was added at baseline and increased to 10 mg at 1 week.

Nitesh D. Kuhadiya

At the end of 12 weeks of triple therapy, patients saw reductions in mean HbA1c (0.66%, P = 0.0004); mean glucose level (28 mg/dL, P = 0.016); mean body weight (2 kg, P = 0.02)’ and mean BMI (1 kg/m², P = 0.02). Total insulin dose was 0.7 u/kg daily and was unchanged from baseline. Patients saw an 11% increase in time spent in the target glycemic range of 70 mg.dL to 160 mg/dL, while time spent with glycemic levels greater than 160 mg/dL decreased by 13% (P < .05 for both). No additional hypoglycemia was observed (< 70 mg/dL).

Diabetic ketoacidosis was noted in a single patient, who maintained normal blood glucose concentrations within 48 hours of increasing the dose of dapagliflozin to 10 mg; this patient’s insulin dose had been reduced from 0.45 u/kg to 0.39 u/kg (total dose: 32.9 to 28.5 units).

“The use of both liraglutide ... and dapagliflozin ... is considered off-label at the current time, and so it should only be used by an experienced endocrinologist who can carefully titrate the insulin doses, particularly in patients with type 1 diabetes,” Kuhadiya told Endocrine Today. “We also have to be careful about risk of euglycemic diabetic ketoacidosis because ... Farxiga also reduces blood sugars, but it could [trigger] diabetic ketoacidosis because your insulin requirements might fall to that critical level of 0.5 units/kg of body weight and below. At that level your blood sugars might still be OK because you don’t need as much insulin, but you need at least that amount to switch off the process of ketogenesis.” – by Jill Rollet

Reference:

Kuhadiya ND, et al. Abstract 130-LB. Presented at: American Diabetes Association’s 75th Scientific Sessions; June 5-9, 2015; Boston.

Disclosure: Kuhadiya reports no relevant financial relationships.