Glucagon-like peptide-1 (GLP-1) receptor agonists (RA) reduce appetite and energy intake. Recent findings from animal studies suggest a role of GLP-1 in drinking and water homeostasis. We aimed to elucidate whether GLP-1 RA reduce fluid intake in healthy volunteers.

Double-blind, randomized, placebo-controlled, crossover study. 20 healthy volunteers received dulaglutide 1.5 mg and placebo (0,9% sodium chloride) subcutaneously once weekly for 3 weeks. At the end of each treatment period, participants attended an 8-h evaluation visit, during which they were requested to eat two standardized meals and to drink water ad libitum. The primary outcome was the total fluid intake (ml) during the evaluation visit.

Mean [SD] age of participants (60% female) was 27 [9.2] years. All but four participants drank less on dulaglutide versus placebo treatment despite identical food intake. The median [IQR] difference of fluid intake on dulaglutide compared to placebo treatment was −100 ml [−400–0]. Median [IQR] total fluid intake was 1300 ml [888–1600] versus 1600 ml [1000–1720], on dulaglutide and placebo treatment, p = 0.06. Median [IQR] 24-h urine output was reduced in dulaglutide versus placebo-treated participants: 1250 ml [975–2080] versus 1680 ml [1400–2040], p = 0.04. Median serum sodium levels were 140 mmol/L on both visits and no difference in thirst perception was noted.

GLP-1 RA such as dulaglutide seem to modulate fluid balance in humans. This leads us to speculate that GLP-1 RA may be an interesting therapeutic options for patients with excessive drinking behavior e.g., primary polydipsia.