Effects of Liraglutide on Weight Loss, Fat Distribution, and β-Cell Function in Obese Subjects With Prediabetes or Early Type 2 Diabetes

Francesca Santilli; Paola G Simeone; Maria T Guagnano; Marika Leo; Marica T Maccarone; Augusto Di Castelnuovo; Cristina Sborgia; Riccardo C Bonadonna; Ermanno Angelucci; Virginia Federico; Stefano Cianfarani; Lamberto Manzoli; Giovanni Davì; Armando Tartaro; Agostino Consoli

doi:10.2337/dc17-0589

Effects of Liraglutide on Weight Loss, Fat Distribution, and β-Cell Function in Obese Subjects With Prediabetes or Early Type 2 Diabetes

Francesca Santilli, Paola G Simeone, Maria T Guagnano, Marika Leo, Marica T Maccarone, Augusto Di Castelnuovo, Cristina Sborgia, Riccardo C Bonadonna, Ermanno Angelucci, Virginia Federico, Stefano Cianfarani, Lamberto Manzoli, Giovanni Davì, Armando Tartaro, Agostino Consoli

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Abstract

OBJECTIVE: Obesity is associated with an increased risk of type 2 diabetes and cardiovascular complications. The risk depends significantly on adipose tissue distribution. Liraglutide, a glucagon-like peptide 1 analog, is associated with weight loss, improved glycemic control, and reduced cardiovascular risk. We determined whether an equal degree of weight loss by liraglutide or lifestyle changes has a different impact on subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) in obese subjects with prediabetes or early type 2 diabetes.

RESEARCH DESIGN AND METHODS: Sixty-two metformin-treated obese subjects with prediabetes or newly diagnosed type 2 diabetes, were randomized to liraglutide (1.8 mg/day) or lifestyle counseling. Changes in SAT and VAT levels (determined by abdominal MRI), insulin sensitivity (according to the Matsuda index), and β-cell function (β-index) were assessed during a multiple-sampling oral glucose tolerance test; and circulating levels of IGF-I and IGF-II were assessed before and after a comparable weight loss (7% of initial body weight).

RESULTS: After comparable weight loss, achieved by 20 patients per arm, and superimposable glycemic control, as reflected by HbA1c level (P = 0.60), reduction in VAT was significantly higher in the liraglutide arm than in the lifestyle arm (P = 0.028), in parallel with a greater improvement in β-index (P = 0.021). No differences were observed in SAT reduction (P = 0.64). IGF-II serum levels were significantly increased (P = 0.024) only with liraglutide administration, and the increase in IGF-II levels correlated with both a decrease in VAT (ρ = -0.435, P = 0.056) and an increase in the β-index (ρ = 0.55, P = 0.012).

CONCLUSIONS: Liraglutide effects on visceral obesity and β-cell function might provide a rationale for using this molecule in obese subjects in an early phase of glucose metabolism dysregulation natural history.

Original language	English
Pages (from-to)	1556-1564
Number of pages	9
Journal	Diabetes Care
Volume	40
Issue number	11
DOIs	https://doi.org/10.2337/dc17-0589
Publication status	Published - Nov 2017

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Santilli, F., Simeone, P. G., Guagnano, M. T., Leo, M., Maccarone, M. T., Di Castelnuovo, A., Sborgia, C., Bonadonna, R. C., Angelucci, E., Federico, V., Cianfarani, S., Manzoli, L., Davì, G., Tartaro, A., & Consoli, A. (2017). Effects of Liraglutide on Weight Loss, Fat Distribution, and β-Cell Function in Obese Subjects With Prediabetes or Early Type 2 Diabetes. Diabetes Care, 40(11), 1556-1564. https://doi.org/10.2337/dc17-0589

Effects of Liraglutide on Weight Loss, Fat Distribution, and β-Cell Function in Obese Subjects With Prediabetes or Early Type 2 Diabetes. / Santilli, Francesca; Simeone, Paola G; Guagnano, Maria T; Leo, Marika; Maccarone, Marica T; Di Castelnuovo, Augusto; Sborgia, Cristina; Bonadonna, Riccardo C; Angelucci, Ermanno; Federico, Virginia; Cianfarani, Stefano; Manzoli, Lamberto; Davì, Giovanni; Tartaro, Armando; Consoli, Agostino.

In: Diabetes Care, Vol. 40, No. 11, 11.2017, p. 1556-1564.

Research output: Contribution to journal › Article › peer-review

Santilli, F, Simeone, PG, Guagnano, MT, Leo, M, Maccarone, MT, Di Castelnuovo, A, Sborgia, C, Bonadonna, RC, Angelucci, E, Federico, V, Cianfarani, S, Manzoli, L, Davì, G, Tartaro, A & Consoli, A 2017, 'Effects of Liraglutide on Weight Loss, Fat Distribution, and β-Cell Function in Obese Subjects With Prediabetes or Early Type 2 Diabetes', Diabetes Care, vol. 40, no. 11, pp. 1556-1564. https://doi.org/10.2337/dc17-0589

Santilli, Francesca ; Simeone, Paola G ; Guagnano, Maria T ; Leo, Marika ; Maccarone, Marica T ; Di Castelnuovo, Augusto ; Sborgia, Cristina ; Bonadonna, Riccardo C ; Angelucci, Ermanno ; Federico, Virginia ; Cianfarani, Stefano ; Manzoli, Lamberto ; Davì, Giovanni ; Tartaro, Armando ; Consoli, Agostino. / Effects of Liraglutide on Weight Loss, Fat Distribution, and β-Cell Function in Obese Subjects With Prediabetes or Early Type 2 Diabetes. In: Diabetes Care. 2017 ; Vol. 40, No. 11. pp. 1556-1564.

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title = "Effects of Liraglutide on Weight Loss, Fat Distribution, and β-Cell Function in Obese Subjects With Prediabetes or Early Type 2 Diabetes",

abstract = "OBJECTIVE: Obesity is associated with an increased risk of type 2 diabetes and cardiovascular complications. The risk depends significantly on adipose tissue distribution. Liraglutide, a glucagon-like peptide 1 analog, is associated with weight loss, improved glycemic control, and reduced cardiovascular risk. We determined whether an equal degree of weight loss by liraglutide or lifestyle changes has a different impact on subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) in obese subjects with prediabetes or early type 2 diabetes.RESEARCH DESIGN AND METHODS: Sixty-two metformin-treated obese subjects with prediabetes or newly diagnosed type 2 diabetes, were randomized to liraglutide (1.8 mg/day) or lifestyle counseling. Changes in SAT and VAT levels (determined by abdominal MRI), insulin sensitivity (according to the Matsuda index), and β-cell function (β-index) were assessed during a multiple-sampling oral glucose tolerance test; and circulating levels of IGF-I and IGF-II were assessed before and after a comparable weight loss (7% of initial body weight).RESULTS: After comparable weight loss, achieved by 20 patients per arm, and superimposable glycemic control, as reflected by HbA1c level (P = 0.60), reduction in VAT was significantly higher in the liraglutide arm than in the lifestyle arm (P = 0.028), in parallel with a greater improvement in β-index (P = 0.021). No differences were observed in SAT reduction (P = 0.64). IGF-II serum levels were significantly increased (P = 0.024) only with liraglutide administration, and the increase in IGF-II levels correlated with both a decrease in VAT (ρ = -0.435, P = 0.056) and an increase in the β-index (ρ = 0.55, P = 0.012).CONCLUSIONS: Liraglutide effects on visceral obesity and β-cell function might provide a rationale for using this molecule in obese subjects in an early phase of glucose metabolism dysregulation natural history.",

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author = "Francesca Santilli and Simeone, {Paola G} and Guagnano, {Maria T} and Marika Leo and Maccarone, {Marica T} and {Di Castelnuovo}, Augusto and Cristina Sborgia and Bonadonna, {Riccardo C} and Ermanno Angelucci and Virginia Federico and Stefano Cianfarani and Lamberto Manzoli and Giovanni Dav{\`i} and Armando Tartaro and Agostino Consoli",

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T1 - Effects of Liraglutide on Weight Loss, Fat Distribution, and β-Cell Function in Obese Subjects With Prediabetes or Early Type 2 Diabetes

AU - Santilli, Francesca

AU - Simeone, Paola G

AU - Guagnano, Maria T

AU - Leo, Marika

AU - Maccarone, Marica T

AU - Di Castelnuovo, Augusto

AU - Sborgia, Cristina

AU - Bonadonna, Riccardo C

AU - Angelucci, Ermanno

AU - Federico, Virginia

AU - Cianfarani, Stefano

AU - Manzoli, Lamberto

AU - Davì, Giovanni

AU - Tartaro, Armando

AU - Consoli, Agostino

PY - 2017/11

Y1 - 2017/11

N2 - OBJECTIVE: Obesity is associated with an increased risk of type 2 diabetes and cardiovascular complications. The risk depends significantly on adipose tissue distribution. Liraglutide, a glucagon-like peptide 1 analog, is associated with weight loss, improved glycemic control, and reduced cardiovascular risk. We determined whether an equal degree of weight loss by liraglutide or lifestyle changes has a different impact on subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) in obese subjects with prediabetes or early type 2 diabetes.RESEARCH DESIGN AND METHODS: Sixty-two metformin-treated obese subjects with prediabetes or newly diagnosed type 2 diabetes, were randomized to liraglutide (1.8 mg/day) or lifestyle counseling. Changes in SAT and VAT levels (determined by abdominal MRI), insulin sensitivity (according to the Matsuda index), and β-cell function (β-index) were assessed during a multiple-sampling oral glucose tolerance test; and circulating levels of IGF-I and IGF-II were assessed before and after a comparable weight loss (7% of initial body weight).RESULTS: After comparable weight loss, achieved by 20 patients per arm, and superimposable glycemic control, as reflected by HbA1c level (P = 0.60), reduction in VAT was significantly higher in the liraglutide arm than in the lifestyle arm (P = 0.028), in parallel with a greater improvement in β-index (P = 0.021). No differences were observed in SAT reduction (P = 0.64). IGF-II serum levels were significantly increased (P = 0.024) only with liraglutide administration, and the increase in IGF-II levels correlated with both a decrease in VAT (ρ = -0.435, P = 0.056) and an increase in the β-index (ρ = 0.55, P = 0.012).CONCLUSIONS: Liraglutide effects on visceral obesity and β-cell function might provide a rationale for using this molecule in obese subjects in an early phase of glucose metabolism dysregulation natural history.

AB - OBJECTIVE: Obesity is associated with an increased risk of type 2 diabetes and cardiovascular complications. The risk depends significantly on adipose tissue distribution. Liraglutide, a glucagon-like peptide 1 analog, is associated with weight loss, improved glycemic control, and reduced cardiovascular risk. We determined whether an equal degree of weight loss by liraglutide or lifestyle changes has a different impact on subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) in obese subjects with prediabetes or early type 2 diabetes.RESEARCH DESIGN AND METHODS: Sixty-two metformin-treated obese subjects with prediabetes or newly diagnosed type 2 diabetes, were randomized to liraglutide (1.8 mg/day) or lifestyle counseling. Changes in SAT and VAT levels (determined by abdominal MRI), insulin sensitivity (according to the Matsuda index), and β-cell function (β-index) were assessed during a multiple-sampling oral glucose tolerance test; and circulating levels of IGF-I and IGF-II were assessed before and after a comparable weight loss (7% of initial body weight).RESULTS: After comparable weight loss, achieved by 20 patients per arm, and superimposable glycemic control, as reflected by HbA1c level (P = 0.60), reduction in VAT was significantly higher in the liraglutide arm than in the lifestyle arm (P = 0.028), in parallel with a greater improvement in β-index (P = 0.021). No differences were observed in SAT reduction (P = 0.64). IGF-II serum levels were significantly increased (P = 0.024) only with liraglutide administration, and the increase in IGF-II levels correlated with both a decrease in VAT (ρ = -0.435, P = 0.056) and an increase in the β-index (ρ = 0.55, P = 0.012).CONCLUSIONS: Liraglutide effects on visceral obesity and β-cell function might provide a rationale for using this molecule in obese subjects in an early phase of glucose metabolism dysregulation natural history.

KW - Journal Article

U2 - 10.2337/dc17-0589

DO - 10.2337/dc17-0589

M3 - Article

C2 - 28912305

VL - 40

SP - 1556

EP - 1564

JO - Diabetes Care

JF - Diabetes Care

SN - 1935-5548

IS - 11

ER -

Effects of Liraglutide on Weight Loss, Fat Distribution, and β-Cell Function in Obese Subjects With Prediabetes or Early Type 2 Diabetes

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