Sumatriptan, a serotonin 5HT1B receptor agonist, acutely reduces insulin secretion and sensitivity and glucose effectiveness in overweight humans: A double‐blinded placebo‐controlled cross‐over trial

Abstract

AbstractAimEvidence from mouse models suggests that brain serotonergic pathways control blood glucose. We hypothesized that sumatriptan (5HT1B‐receptor agonist) would alter glucose homeostasis in humans.Materials and MethodsWe conducted a two‐visit random‐order double‐blinded placebo‐controlled cross‐over trial in 10 overweight adults that were otherwise healthy. Participants received sumatriptan (single dose, 100 mg) or placebo before undergoing a 60‐min intravenous glucose tolerance test, followed by a 120‐min hyperinsulinaemic euglycaemic clamp.ResultsGlucose excursion was greater during intravenous glucose tolerance test with sumatriptan compared with placebo [iAUC0‐60 min 316 (268‐333) vs. 251 (197‐319) min/mmol/L p = .047]. This was probably explained by a combination of reduced circulating insulin levels [iAUC0‐10 min 1626 (1103‐2733) vs. 2336 (1702‐3269) min/pmol/L, p = .005], reduced insulin sensitivity [M/I‐value 2.11 (1.15, 4.05) vs. 3.03 (1.14, 4.90) mg/kg/min per pmol/L, p = .010] and glucose effectiveness [SG 0.17 (0.12, 0.21) vs. 0.22 (0.18, 0.65)/min, p = .027].Conclusions5HT1B receptors have a glucoregulatory role in humans, probably acting on insulin secretion, insulin sensitivity and glucose effectiveness.