Objective: GLP-1 has been investigated in regulation of reproductive system in animal models. Current observations suggest that it directly regulates kisspeptin and GnRH expression and that ovaries express GLP-1 mRNA.

Aim: To evaluate the impact of low dose liraglutide in combination with metformin compared to metformin alone on IVF pregnancy rate (PR) and cumulatively PR (IVF and spontaneous) in infertile obese women with PCOS who had been previously poor responders regarding weight reduction with lifestyle modification and resistant to first line reproductive treatments.

Design/Participants/Methods: A prospective randomized open-label study was conducted with 28 infertile obese PCOS patients (aged 31,07±4,75 years, BMI 36,7±3,5 kg/m2, mean ± SD). They were assigned to metformin (MET) 1000 mg BID or combined MET 1000 mg BID and low dose liraglutide 1.2 mg QD s.c. (COMBI) for 12 weeks. Ovarian stimulation protocol was started after 4-week medication free period.

Results: Patients in MET lost on average 7,0±6,0 kg (P<0.001) compared with 7,5± 3,9 kg loss in COMBI group (P<0.001), with no significant between-treatment difference (P=0,103). All treatment interventions resulted in significant reduction of visceral adipose tissue as assessed by DXA and reduction of HOMA-IR (p<0.001), with no significant difference regarding the treatment employed. After intervention, PR per ET was significantly higher in COMBI (85,7%) compared with MET (28,6%) (P=0.03). Moreover, cumulatively PR in time frame of 12 months in COMBI was 69,2% compared to 35,7% in MET.

Conclusion: Short-term preconception intervention with low dose liraglutide as an add on to metformin was superior to metformin alone in increasing PR per ET and cumulative PR in infertile obese PCOS, despite comparable weight reduction in both arms. Potential direct crosstalk between GLP-1 and reproductive system needs further exploration.


A. Janez: None. M. Jensterle: None.

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