TY - JOUR
T1 - Combination GLP-1 and Insulin Treatment Fails to Alter Myocardial Fuel Selection vs. Insulin Alone in Type 2 Diabetes
AU - Mather, Kieren J.
AU - Considine, Robert V.
AU - Hamilton, Latonya
AU - Patel, Niral A.
AU - Mathias, Carla
AU - Territo, Wendy
AU - Goodwill, Adam G.
AU - Tune, Johnathan D.
AU - Green, Mark A.
AU - Hutchins, Gary D.
N1 - Funding Information:
Financial Support: This project was supported by an Investigator Initiated Trial grant from Novo Nordisk, and by funding from the National Institutes of Health (Grant HL117620 to J.D.T. and K.J.M.). The Indiana Clinical and Translational Sciences Institute is supported by National Institutes of Health Grants UL1TR001108, TR000006, and RR025671. The sponsors had no access to or influence over the data analyses and did not participate in preparation of the study report.
Publisher Copyright:
© 2018 Endocrine Society.
PY - 2018/9/1
Y1 - 2018/9/1
N2 - Context: It is unclear if effects of glucagon-like peptide-1 (GLP-1) and clinically available GLP-1 agonists on the heart occur at clinical doses in humans, possibly contributing to reduced cardiovascular disease risk. Objective: To determine whether liraglutide, at clinical dosing, augments myocardial glucose uptake (MGU) alone or combined with insulin compared with insulin alone in metformin-treated type 2 diabetes mellitus (T2D). Design: In a randomized clinical trial of patients with T2D treated with metformin plus oral agents or basal insulin, myocardial fuel use was compared after 3 months of treatment with insulin detemir, liraglutide, or combination detemir plus liraglutide added to background metformin. Main Outcome Measures: Myocardial blood flow (MBF), fuel selection, and rates of fuel use were evaluated using positron emission tomography, powered to demonstrate large effects. Results: MBF was greater in the insulin-treated groups [median (25th, 75th percentile): detemir, 0.64 mL/g/min (0.50, 0.69); liraglutide, 0.52 mL/g/min (0.46, 0.58); detemir plus liraglutide, 0.75 mL/g/min (0.55, 0.77); P = 0.035 comparing three groups, P = 0.01 comparing detemir groups to liraglutide alone]. There were no evident differences among groups in MGU [detemir, 0.040 mmol/g/min (0.013, 0.049); liraglutide, 0.055 mmol/g/min (0.019, 0.105); detemir plus liraglutide, 0.037 mmol/g/min (0.009, 0.046); P = 0.68 comparing three groups]. There were no treatment-group differences in measures of myocardial fatty acid uptake or handling, and no differences in total oxidation rate. Conclusion: These observations argue against large effects of GLP-1 agonists on myocardial fuel metabolism as mediators of beneficial treatment effects on myocardial function and ischemia protection.
AB - Context: It is unclear if effects of glucagon-like peptide-1 (GLP-1) and clinically available GLP-1 agonists on the heart occur at clinical doses in humans, possibly contributing to reduced cardiovascular disease risk. Objective: To determine whether liraglutide, at clinical dosing, augments myocardial glucose uptake (MGU) alone or combined with insulin compared with insulin alone in metformin-treated type 2 diabetes mellitus (T2D). Design: In a randomized clinical trial of patients with T2D treated with metformin plus oral agents or basal insulin, myocardial fuel use was compared after 3 months of treatment with insulin detemir, liraglutide, or combination detemir plus liraglutide added to background metformin. Main Outcome Measures: Myocardial blood flow (MBF), fuel selection, and rates of fuel use were evaluated using positron emission tomography, powered to demonstrate large effects. Results: MBF was greater in the insulin-treated groups [median (25th, 75th percentile): detemir, 0.64 mL/g/min (0.50, 0.69); liraglutide, 0.52 mL/g/min (0.46, 0.58); detemir plus liraglutide, 0.75 mL/g/min (0.55, 0.77); P = 0.035 comparing three groups, P = 0.01 comparing detemir groups to liraglutide alone]. There were no evident differences among groups in MGU [detemir, 0.040 mmol/g/min (0.013, 0.049); liraglutide, 0.055 mmol/g/min (0.019, 0.105); detemir plus liraglutide, 0.037 mmol/g/min (0.009, 0.046); P = 0.68 comparing three groups]. There were no treatment-group differences in measures of myocardial fatty acid uptake or handling, and no differences in total oxidation rate. Conclusion: These observations argue against large effects of GLP-1 agonists on myocardial fuel metabolism as mediators of beneficial treatment effects on myocardial function and ischemia protection.
UR - http://www.scopus.com/inward/record.url?scp=85054127728&partnerID=8YFLogxK
U2 - 10.1210/jc.2018-00712
DO - 10.1210/jc.2018-00712
M3 - Article
C2 - 30020461
AN - SCOPUS:85054127728
SN - 0021-972X
VL - 103
SP - 3456
EP - 3465
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
IS - 9
ER -