Effect of Medical and Surgical Interventions on α-Cell Function in Dysglycemic Youth and Adults in the RISE Study
Research Design and Methods: Glucagon was measured in three randomized, parallel, clinical studies: (1) 91 youth studied at baseline, after 12 months on metformin alone (MET) or glargine followed by metformin (G/M), and 3 months after treatment withdrawal; (2) 267 adults studied at the same timepoints and treated with MET, G/M, liraglutide plus metformin (L+M) or placebo (PLAC); and (3) 88 adults studied at baseline, and after 12 and 24 months of LB or MET. Fasting glucagon, glucagon suppression by glucose and acute glucagon response (AGR) to arginine were assessed during hyperglycemic clamps. Glucagon suppression was also measured during oral glucose tolerance tests (OGTTs).
Results: No change in fasting glucagon, steady-state glucagon or AGR was seen at 12 months following treatment with MET or G/M (in youth and adults) or PLAC (in adults). In contrast, L+M reduced these measures at 12 months (all p≤0.005), which was maintained three months after treatment withdrawal (all p<0.01). LB in adults also reduced fasting glucagon, steady-state glucagon and AGR at 12 and 24 months (p<0.05 for all, except AGR at 12 months [p=0.098]). Similarly, glucagon suppression during OGTTs was greater with L+M and LB. Linear models demonstrated that treatment effects on glucagon with L+M and LB were largely associated with weight loss.
Conclusions: Glucagon concentrations were reduced by L+M and LB in adults with dysglycemia, an effect principally attributed to weight loss in both interventions.