Liraglutide effects on beta-cell, insulin sensitivity and glucose effectiveness in patients with stable coronary artery disease and newly diagnosed type 2 diabetes

Christian Anholm; Preman Kumarathurai; Lene R. Pedersen; Olav W. Nielsen; Ole P. Kristiansen; Mogens Fenger; Sten Madsbad; Ahmad Sajadieh; Steen B. Haugaard

doi:10.1111/dom.12891

Liraglutide effects on beta-cell, insulin sensitivity and glucose effectiveness in patients with stable coronary artery disease and newly diagnosed type 2 diabetes

Christian Anholm^*, Preman Kumarathurai, Lene R. Pedersen, Olav W. Nielsen, Ole P. Kristiansen, Mogens Fenger, Sten Madsbad, Ahmad Sajadieh, Steen B. Haugaard

^*Corresponding author for this work

12 Citations (Scopus)

Abstract

Aims: The aims of the study were to investigate the effects of the GLP-1 receptor agonist liraglutide as add-on to metformin on insulin sensitivity (Si) and glucose effectiveness (Sg) in addition to its positive effects on beta-cell function in overweight/obese patients with coronary artery disease (CAD) and type 2 diabetes mellitus (T2DM). Methods: The design of the study was a randomized, double-blind, placebo-controlled, cross-over trial in patients with stable CAD and newly diagnosed well-controlled T2DM. Patients were treated with liraglutide/metformin vs placebo/metformin for a 12 + 12-week period with ≥2-week wash-out. First phase insulin secretion (AIRg), Si and Sg were estimated by the Bergman Minimal Model, enabling calculation of beta-cell function; Disposition Index (DI) = AIRg × Si. A total of 30 patients from among 41 randomized were available for paired analysis. Results: Baseline characteristics were: HbA1c 47 mmol/mol (SD 6), BMI 31.6 kg/m² (SD 4.8), fasting plasma-glucose 6.9 mmol/L (IQR 6.1; 7.4) and HOMA-IR 4.9 (IQR 3.0; 7.5). Liraglutide treatment improved AIRg by 3-fold, 497 mU × L⁻¹ × min (IQR 342; 626, P <.0001) and DI by 1-fold, 766 (SD 824, P <.0001). Despite a significant weight loss of −2.7 kg (−6.7; −0.6) during liraglutide treatment, we found no improvement in HOMA-IR, Si or Sg. Weight loss during liraglutide therapy did not result in a carry-over effect. Conclusion: Liraglutide as add-on to metformin induces a clinically significant improvement in beta-cell function in overweight/obese, high cardiovascular risk patients with newly diagnosed well-controlled T2DM and CAD. The effect of liraglutide on DI is mediated entirely by improved AIRg whereas the effects on Si and Sg are neutral.

Original language	English
Journal	Diabetes, Obesity and Metabolism
Volume	19
Issue number	6
Pages (from-to)	850-857
ISSN	1462-8902
DOIs	https://doi.org/10.1111/dom.12891
Publication status	Published - 2017

Keywords

beta-cell function
glucose effectiveness
insulin sensitivity
liraglutide
type 2 diabetes

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1111/dom.12891

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Anholm, C., Kumarathurai, P., Pedersen, L. R., Nielsen, O. W., Kristiansen, O. P., Fenger, M., Madsbad, S., Sajadieh, A., & Haugaard, S. B. (2017). Liraglutide effects on beta-cell, insulin sensitivity and glucose effectiveness in patients with stable coronary artery disease and newly diagnosed type 2 diabetes. Diabetes, Obesity and Metabolism, 19(6), 850-857. https://doi.org/10.1111/dom.12891

Liraglutide effects on beta-cell, insulin sensitivity and glucose effectiveness in patients with stable coronary artery disease and newly diagnosed type 2 diabetes. / Anholm, Christian; Kumarathurai, Preman; Pedersen, Lene R. et al.
In: Diabetes, Obesity and Metabolism, Vol. 19, No. 6, 2017, p. 850-857.

Research output: Contribution to journal › Journal article › Research › peer-review

Anholm, C, Kumarathurai, P, Pedersen, LR, Nielsen, OW, Kristiansen, OP, Fenger, M, Madsbad, S , Sajadieh, A & Haugaard, SB 2017, 'Liraglutide effects on beta-cell, insulin sensitivity and glucose effectiveness in patients with stable coronary artery disease and newly diagnosed type 2 diabetes', Diabetes, Obesity and Metabolism, vol. 19, no. 6, pp. 850-857. https://doi.org/10.1111/dom.12891

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title = "Liraglutide effects on beta-cell, insulin sensitivity and glucose effectiveness in patients with stable coronary artery disease and newly diagnosed type 2 diabetes",

abstract = "Aims: The aims of the study were to investigate the effects of the GLP-1 receptor agonist liraglutide as add-on to metformin on insulin sensitivity (Si) and glucose effectiveness (Sg) in addition to its positive effects on beta-cell function in overweight/obese patients with coronary artery disease (CAD) and type 2 diabetes mellitus (T2DM). Methods: The design of the study was a randomized, double-blind, placebo-controlled, cross-over trial in patients with stable CAD and newly diagnosed well-controlled T2DM. Patients were treated with liraglutide/metformin vs placebo/metformin for a 12 + 12-week period with ≥2-week wash-out. First phase insulin secretion (AIRg), Si and Sg were estimated by the Bergman Minimal Model, enabling calculation of beta-cell function; Disposition Index (DI) = AIRg × Si. A total of 30 patients from among 41 randomized were available for paired analysis. Results: Baseline characteristics were: HbA1c 47 mmol/mol (SD 6), BMI 31.6 kg/m2 (SD 4.8), fasting plasma-glucose 6.9 mmol/L (IQR 6.1; 7.4) and HOMA-IR 4.9 (IQR 3.0; 7.5). Liraglutide treatment improved AIRg by 3-fold, 497 mU × L−1 × min (IQR 342; 626, P <.0001) and DI by 1-fold, 766 (SD 824, P <.0001). Despite a significant weight loss of −2.7 kg (−6.7; −0.6) during liraglutide treatment, we found no improvement in HOMA-IR, Si or Sg. Weight loss during liraglutide therapy did not result in a carry-over effect. Conclusion: Liraglutide as add-on to metformin induces a clinically significant improvement in beta-cell function in overweight/obese, high cardiovascular risk patients with newly diagnosed well-controlled T2DM and CAD. The effect of liraglutide on DI is mediated entirely by improved AIRg whereas the effects on Si and Sg are neutral.",

keywords = "beta-cell function, glucose effectiveness, insulin sensitivity, liraglutide, type 2 diabetes",

author = "Christian Anholm and Preman Kumarathurai and Pedersen, {Lene R.} and Nielsen, {Olav W.} and Kristiansen, {Ole P.} and Mogens Fenger and Sten Madsbad and Ahmad Sajadieh and Haugaard, {Steen B.}",

year = "2017",

doi = "10.1111/dom.12891",

language = "English",

volume = "19",

pages = "850--857",

journal = "Diabetes, Obesity and Metabolism",

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T1 - Liraglutide effects on beta-cell, insulin sensitivity and glucose effectiveness in patients with stable coronary artery disease and newly diagnosed type 2 diabetes

AU - Anholm, Christian

AU - Kumarathurai, Preman

AU - Pedersen, Lene R.

AU - Nielsen, Olav W.

AU - Kristiansen, Ole P.

AU - Fenger, Mogens

AU - Madsbad, Sten

AU - Sajadieh, Ahmad

AU - Haugaard, Steen B.

PY - 2017

Y1 - 2017

N2 - Aims: The aims of the study were to investigate the effects of the GLP-1 receptor agonist liraglutide as add-on to metformin on insulin sensitivity (Si) and glucose effectiveness (Sg) in addition to its positive effects on beta-cell function in overweight/obese patients with coronary artery disease (CAD) and type 2 diabetes mellitus (T2DM). Methods: The design of the study was a randomized, double-blind, placebo-controlled, cross-over trial in patients with stable CAD and newly diagnosed well-controlled T2DM. Patients were treated with liraglutide/metformin vs placebo/metformin for a 12 + 12-week period with ≥2-week wash-out. First phase insulin secretion (AIRg), Si and Sg were estimated by the Bergman Minimal Model, enabling calculation of beta-cell function; Disposition Index (DI) = AIRg × Si. A total of 30 patients from among 41 randomized were available for paired analysis. Results: Baseline characteristics were: HbA1c 47 mmol/mol (SD 6), BMI 31.6 kg/m2 (SD 4.8), fasting plasma-glucose 6.9 mmol/L (IQR 6.1; 7.4) and HOMA-IR 4.9 (IQR 3.0; 7.5). Liraglutide treatment improved AIRg by 3-fold, 497 mU × L−1 × min (IQR 342; 626, P <.0001) and DI by 1-fold, 766 (SD 824, P <.0001). Despite a significant weight loss of −2.7 kg (−6.7; −0.6) during liraglutide treatment, we found no improvement in HOMA-IR, Si or Sg. Weight loss during liraglutide therapy did not result in a carry-over effect. Conclusion: Liraglutide as add-on to metformin induces a clinically significant improvement in beta-cell function in overweight/obese, high cardiovascular risk patients with newly diagnosed well-controlled T2DM and CAD. The effect of liraglutide on DI is mediated entirely by improved AIRg whereas the effects on Si and Sg are neutral.

AB - Aims: The aims of the study were to investigate the effects of the GLP-1 receptor agonist liraglutide as add-on to metformin on insulin sensitivity (Si) and glucose effectiveness (Sg) in addition to its positive effects on beta-cell function in overweight/obese patients with coronary artery disease (CAD) and type 2 diabetes mellitus (T2DM). Methods: The design of the study was a randomized, double-blind, placebo-controlled, cross-over trial in patients with stable CAD and newly diagnosed well-controlled T2DM. Patients were treated with liraglutide/metformin vs placebo/metformin for a 12 + 12-week period with ≥2-week wash-out. First phase insulin secretion (AIRg), Si and Sg were estimated by the Bergman Minimal Model, enabling calculation of beta-cell function; Disposition Index (DI) = AIRg × Si. A total of 30 patients from among 41 randomized were available for paired analysis. Results: Baseline characteristics were: HbA1c 47 mmol/mol (SD 6), BMI 31.6 kg/m2 (SD 4.8), fasting plasma-glucose 6.9 mmol/L (IQR 6.1; 7.4) and HOMA-IR 4.9 (IQR 3.0; 7.5). Liraglutide treatment improved AIRg by 3-fold, 497 mU × L−1 × min (IQR 342; 626, P <.0001) and DI by 1-fold, 766 (SD 824, P <.0001). Despite a significant weight loss of −2.7 kg (−6.7; −0.6) during liraglutide treatment, we found no improvement in HOMA-IR, Si or Sg. Weight loss during liraglutide therapy did not result in a carry-over effect. Conclusion: Liraglutide as add-on to metformin induces a clinically significant improvement in beta-cell function in overweight/obese, high cardiovascular risk patients with newly diagnosed well-controlled T2DM and CAD. The effect of liraglutide on DI is mediated entirely by improved AIRg whereas the effects on Si and Sg are neutral.

KW - beta-cell function

KW - glucose effectiveness

KW - insulin sensitivity

KW - liraglutide

KW - type 2 diabetes

U2 - 10.1111/dom.12891

DO - 10.1111/dom.12891

M3 - Journal article

C2 - 28124822

AN - SCOPUS:85013684704

SN - 1462-8902

VL - 19

SP - 850

EP - 857

JO - Diabetes, Obesity and Metabolism

JF - Diabetes, Obesity and Metabolism

IS - 6

ER -

Liraglutide effects on beta-cell, insulin sensitivity and glucose effectiveness in patients with stable coronary artery disease and newly diagnosed type 2 diabetes

Abstract

Keywords

UN SDGs

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