One-year follow-up on liraglutide treatment for prediabetes and overweight/obesity in clozapine- or olanzapine-treated patients.

OBJECTIVE: Treatment with most antipsychotics is associated with an increased risk of weight gain and metabolic disturbances. In a randomized trial, we previously demonstrated that 16 weeks of glucagon-like peptide-1 receptor agonist liraglutide treatment vs. placebo significantly reduced glucometabolic disturbances and body weight in prediabetic, overweight/obese schizophrenia-spectrum disorder patients treated with clozapine or olanzapine. The aim of this study was to investigate whether the beneficial effects of the 16-week intervention were sustained beyond the intervention period. METHOD: One year after completion of the intervention, we investigated changes in body weight, fasting glucose, glycated hemoglobin, C-peptide, and lipids comparing 1-year follow-up levels to end of treatment (week 16) and baseline (week 0) levels. RESULTS: From end of treatment to the 1-year follow-up, body weight had increased in the liraglutide-treated group. However, compared to baseline levels, the placebo-subtracted body weight loss remained significantly reduced (-3.8 kg, 95% CI: -7.3 to -0.2, P = 0.04). Fasting glucose, glycated hemoglobin, C-peptide, and lipids had each returned to baseline levels 1 year after stopping liraglutide. CONCLUSION: The body weight reduction during 16 weeks of liraglutide treatment was partially sustained 1 year after the intervention was completed. However, the improvements in other metabolic parameters returned to baseline levels.

Postpartum reversibility of impaired incretin effect in gestational diabetes mellitus.

The potential reversibility of a reduced incretin effect is unclear. We investigated the incretin effect during third trimester and 3 to 4months postpartum in women with and without gestational diabetes mellitus (GDM). Ten women with GDM (plasma glucose (PG) concentration at 120min after 75g-oral glucose tolerance test (OGTT) (PG120min): 10.1±0.6mmol/l (mean±SEM)) and eight women with normal glucose tolerance (NGT; PG120min: 7.0±0.1mmol/l) were investigated on four occasions: 4h 50g-OGTT and isoglycaemic intravenous glucose infusion during third trimester and 3 to 4months postpartum. In women with GDM, the incretin effect increased significantly postpartum (31±6 vs. 56±6%, p=0.02), whereas the increment in women with NGT was insignificant (35±12 vs. 56±9%, p=0.08). Similarly, the gastrointestinal-mediated glucose disposal (GIGD=100%×(glucoseOGTT-glucoseIIGI)/glucoseOGTT) was reduced to diabetic levels in women with GDM (37±3%), but increased (p=0.030) to normal levels post partum (58±6%). GIGD did not change significantly in NGT women (48±3 vs. 57±6%, p=0.94). Women with GDM exhibit a reduced incretin effect which is fully reversible alongside the restoration of normal glucose homeostasis, whereas the reduction in incretin effect during pregnancy in women with NGT was insignificant. Our results suggest that decreased incretin effect in women with GDM is a fully reversible phenomenon.