American Diabetes Association (ADA) 75th Scientific Sessions 2015:

Comparative Durability of Second-Line Glucose-Lowering Therapy in Type 2 Diabetes

The durability of glycemic response of various second-line treatment options for type 2 diabetes was the topic of research presented by Jil Mamza, Doctoral Candidate, University of Nottingham, Derby, UK. Mr. Mamza reported results of a large retrospective UK cohort study at the American Diabetes Association’s 75th Scientific Sessions, in Boston, from June 5–9, 2015.

Study Included Over 23,000 Patients
Time to treatment failure was evaluated in 23,261 patients who took a second oral glucose-lowering therapy in addition to metformin between 2007 and 2014. Follow-up lasted 5 years. The primary outcome measured was time to dual therapy failure (defined as time to treatment substitution or intensification using a third-line glucose-lowering therapy when hemoglobin A1C was >58 mmoL/moL, 7.5%).

Risk of events was compared across second-line glucose-lowering therapeutic drug classes, which included sulfonylureas (n=15,508), dipeptidil peptidase 4 inhibitors (n=3080), and thiazolidinediones (n=1482).

Failure Rates at 1 Year
Unadjusted survival analysis showed the incidence of dual therapy failure at 1 year was 15% with sulfonylureas, 23% with dipeptidil peptidase 4 inhibitors, and 8% with thiazolidinediones.

Failure Rates at 2 Years
Corresponding failure rates at 2 years were 26%, 38%, and 12% respectively, for sulfonylureas, dipeptidil peptidase 4 inhibitors, and thiazolidinediones.

Thiazolidinedione Class Demonstrated the Lowest Failure Rate
Adjusted multivariate models showed that, compared to the sulfonylurea group, adding a dipeptidil peptidase 4 inhibitor was associated with an increased hazard of intensification (adjusted hazard ratio 1.58 (1.48, 1.68), while adding a thiazolidinedione was associated with a reduced hazard ratio (0.45 [0.41, 0.50]).

Baseline Parameters That Raised the Failure Rate
Baseline parameters associated with an increased hazard of intensification included hemoglobin A1C, diabetes duration, gender, smoking, and the use of lipid-lowering medication.

Conclusion
This large population study indicates that adding a dipeptidil peptidase 4 inhibitor to metformin was associated with an increased, earlier requirement for treatment intensification compared to adding a sulfonylurea. Use of a thiazolidinedione as second-line glucose-lowering therapy resulted in the most durable glycemic response.

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