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

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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).

MATERIAL AND METHODS: Design: 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-weeks 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 x Si. Thirty patients of 41 randomized were available for paired analysis.

RESULTS: Baseline characteristics: HbA1c 47 mmol/mol (SD 6), BMI 31.6 kg/m(2) (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 < 0.0001) and DI by 1-fold; 766 (SD 824, p < 0.0001). 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 cause a carry-over effect.

CONCLUSION: Liraglutide as add-on to metformin induces a clinical 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.

OriginalsprogEngelsk
TidsskriftDiabetes, Obesity and Metabolism Online
Vol/bind19
Udgave nummer6
Sider (fra-til)850-857
ISSN1463-1326
DOI
StatusUdgivet - 1 jun. 2017

ID: 49799785