A double-blind, placebo-controlled, randomised trial to assess the effect of liraglutide on ectopic fat accumulation in South Asian type 2 diabetes patients

Huub J van Eyk, Elisabeth H M Paiman, Maurice B Bizino, Paul de Heer, Petronella H Geelhoed-Duijvestijn, Aan V Kharagjitsingh, Johannes W A Smit, Hildo J Lamb, Patrick C N Rensen, Ingrid M Jazet, Huub J van Eyk, Elisabeth H M Paiman, Maurice B Bizino, Paul de Heer, Petronella H Geelhoed-Duijvestijn, Aan V Kharagjitsingh, Johannes W A Smit, Hildo J Lamb, Patrick C N Rensen, Ingrid M Jazet

Abstract

Background: South Asians have a high risk to develop type 2 diabetes, which may be related to substantial ectopic fat deposition. Since glucagon-like peptide-1 analogues can reduce ectopic fat accumulation, the aim of the present study was to assess the effect of treatment with liraglutide for 26 weeks on ectopic fat deposition and HbA1c in South Asian patients with type 2 diabetes.

Methods: In a placebo-controlled trial, 47 South Asian patients with type 2 diabetes were randomly assigned to treatment with liraglutide (1.8 mg/day) or placebo added to standard care. At baseline and after 26 weeks of treatment we assessed abdominal subcutaneous, visceral, epicardial and paracardial adipose tissue volume using MRI. Furthermore, myocardial and hepatic triglyceride content were examined with proton magnetic resonance spectroscopy.

Results: In the intention-to-treat analysis, liraglutide decreased body weight compared to placebo (- 3.9 ± 3.6 kg vs - 0.6 ± 2.2 kg; mean change from baseline (liraglutide vs placebo): - 3.5 kg; 95% CI [- 5.3, - 1.8]) without significant effects on the different adipose tissue compartments. HbA1c was decreased in both groups without between group differences. In the per-protocol analysis, liraglutide did decrease visceral adipose tissue volume compared to placebo (- 23 ± 27 cm2 vs - 2 ± 17 cm2; mean change from baseline (liraglutide vs placebo): - 17 cm2; 95% CI [- 32, - 3]). Furthermore, HbA1c was decreased by liraglutide compared to placebo (- 1.0 ± 0.8% (- 10.5 ± 9.1 mmol/mol)) vs (- 0.6 ± 0.8% (- 6.1 ± 8.8 mmol/mol)), with a between group difference (mean change from baseline (liraglutide vs placebo): - 0.6% (- 6.5 mmol/mol); 95% CI [- 1.1, - 0.1 (- 11.5, - 1.5)]). Interestingly, the decrease of visceral adipose tissue volume was associated with the reduction of HbA1c (β: 0.165 mmol/mol (0.015%) per 1 cm2 decrease of visceral adipose tissue volume; 95% CI [0.062, 0.267 (0.006, 0.024%)]).

Conclusions: While the intention-to-treat analysis did not show effects of liraglutide on ectopic fat and HbA1c, per-protocol analysis showed that liraglutide decreases visceral adipose tissue volume, which was associated with improved glycaemic control in South Asians. Trial registration NCT02660047 (clinicaltrials.gov). Registered 21 January 2016.

Keywords: Diabetes mellitus type 2; Ectopic fat; GLP-1 analogue; Liraglutide; Magnetic resonance imaging; Magnetic resonance spectroscopy; Randomised clinical trial; South Asian.

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Trial flow diagram
Fig. 2
Fig. 2
The effect of liraglutide and placebo on different adipose tissue compartments. Percentual changes are depicted after 26 weeks of treatment with liraglutide (n = 24) and placebo (n = 20) compared to baseline. Box and whiskers show 25th and 75th percentile and 10th and 90th percentile, respectively. Missing data in liraglutide-group: n = 3 for epicardial AT and paracardial AT. Missing data in placebo-group: n = 3 for epicardial AT, n = 2 for paracardial AT and n = 1 for Myocardial TGC. AT adipose tissue, TGC triglyceride content. *P < 0.05
Fig. 3
Fig. 3
Associations between the change of adipose tissue compartments and HbA1c after treatment. Subcutaneous AT in relation to HbA1c, n = 44 (a), visceral AT in relation to HbA1c, n = 44 (b), epicardial AT in relation to HbA1c, n = 38 (c), paracardial AT in relation to HbA1c, n = 39 (d), Hepatic TGC in relation to HbA1c, n = 44 (e) and myocardial TGC in relation to HbA1c, n = 43 (f). Regression lines are shown for placebo (open symbol) and liraglutide (closed symbol) combined. AT adipose tissue, TGC triglyceride content

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