Metformin is the first-line therapy for youth-onset type 2 diabetes mellitus (Y-T2D) but is suboptimal in up to 50% of youth. The reasons for increased failure rates are unknown. Metformin plasma concentration reflects total body distribution and kinetics but is not used clinically in adults because peak metformin concentration varies widely. Few studies, and none in youth, have measured trough therapeutic concentration as a potential biomarker of response. We hypothesized that trough metformin plasma concentrations after short-term therapy would be associated with treatment response. In this secondary analysis of a randomized trial of metformin alone vs. metformin and liraglutide (combo) therapy Y-T2D youth, we determined the relationship of metformin concentration with glycemia. Nineteen Y-T2D: age 15.4±2.1 (12-20y) mean±SD (range) , 61% female, Tanner Stage IV-V, BMI 40.0±8.0 (22.1-53.4 kg/m2) were randomized to 2000mg/day metformin (n=10) or 2000mg metformin+ 1.8mg liraglutide (combo, n=8) for 3 months after a 5-7 day drug-free run-in period. At baseline, youth on combo had higher HbA1c (7.1±0.7; 6.2±0.6%, P=0.006) but had similar BMI, fasting glucose, and 2hr glucose on OGTT. Metformin concentrations increased (combo:337±559 vs. metformin: 420±433 (1.6-1537 ng/mL) , P=0.7) and negatively correlated with change in 2hr glucose (combo: r=-0.9, P=0.002; metformin: r=-0.73, P=0.02) , fasting glucose (combo: r=-0.59, P=0.13; metformin: r=-0.64, P=0.06) , and change in HbA1c (combo: r=-0.89, P=0.01, metformin: r=0.31, P=0.4) . Metformin adherence measured by pill counts was 78% with no difference by group (combo: 80±20; metformin: 75±16%) . Metformin concentrations were not associated with percent adherence to medication or change in weight (P>0.10) . Overall, metformin concentrations were widely variable in Y-T2D but associated with improvements in glycemia after 3 months and should be explored as a viable biomarker for predicting treatment response in Y-T2D.
K.B. Dietsche: None. A. Zenno: None. S.A. Dixon: None. L. Mabundo: None. E.L. Shouppe: None. D.E. Estrada: None. F.R. Cogen: None. M. Walter: None. P. Walter: None. S.T. Chung: None.
NIDDK/NIH Intramural Research Program