Mitigating meal-related glycemic excursions in an insulin-sparing manner during closed-loop insulin delivery: The beneficial effects of adjunctive pramlintide and liraglutide

Jennifer L. Sherr, Neha S. Patel, Camille I. Michaud, Miladys M. Palau-Collazo, Michelle A. Van Name, William V. Tamborlane, Eda Cengiz, Lori R. Carria, Eileen M. Tichy, Stuart A. Weinzimer

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Abstract

Objective Closed-loop (CL) insulin delivery effectivelymaintains glucose overnight but struggles when challengedwithmeals. Use of single-day, 30-μg/meal pramlintide lowersmeal excursions during CL. We sought to further elucidate the potential benefits of adjunctive agents after 3-4 weeks of outpatient dose titration. RESEARCH DESIGN AND METHODS Two CL studieswere conducted: one evaluating adjunctive pramlintide and the other liraglutide. Ten subjects (age 16-23 years; A1C 7.2 ± 0.6% [55 ± 6.6 mmol/mol]) completed two 24-h sessions: one on CL alone and one on CL plus 60-mg pramlintide (CL + P), after a 3-4-week outpatient dose escalation. Eleven subjects (age 18-27 years; A1C 7.5 ± 0.9% [58 ± 9.8 mmol/mol]) were studied before and after treatment with 1.8mg liraglutide (CL + L) after a similar 3-4-week dose escalation period. Timing and content of meals during CL were identical within experiments; meals were not announced. RESULTS Pramlintide delayed the time to peak plasma glucose (PG) excursion (CL 1.6 ± 0.5 h vs. CL + P 2.6 ± 0.9 h, P < 0.001) with concomitant blunting of peak postprandial increments in PG (P < 0.0001) and reductions in postmeal incremental PG area under the curve (AUC) (P = 0.0002). CL + L also led to reductions in PG excursions (P = 0.05) and incremental PG AUC (P = 0.004), with a 28% reduction in prandial insulin delivery. Outpatient liraglutide therapy led to a weight loss of 3.2 ± 1.8 kg, with a 26% reduction in total daily insulin dose. CONCLUSIONS Adjunctive pramlintide and liraglutide treatment mitigated postprandial hyperglycemia during CL control; liraglutide demonstrated the additional benefit of weight loss in an insulin-sparingmanner. Further investigations of these and other adjunctive agents in long-term outpatient CL studies are needed.

Original languageEnglish (US)
Pages (from-to)1127-1134
Number of pages8
JournalDiabetes care
Volume39
Issue number7
DOIs
StatePublished - Jul 1 2016

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All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Advanced and Specialized Nursing

Cite this

Sherr, J. L., Patel, N. S., Michaud, C. I., Palau-Collazo, M. M., Van Name, M. A., Tamborlane, W. V., Cengiz, E., Carria, L. R., Tichy, E. M., & Weinzimer, S. A. (2016). Mitigating meal-related glycemic excursions in an insulin-sparing manner during closed-loop insulin delivery: The beneficial effects of adjunctive pramlintide and liraglutide. Diabetes care, 39(7), 1127-1134. https://doi.org/10.2337/dc16-0089