844-P: Effects of Dapagliflozin, Metformin, or Exercise on Plasma Glucagon Concentrations in Individuals with Prediabetes: The PRE-D Trial

Introduction: Glucagon plays a role in the pathogenesis of type 2 diabetes. Yet, little is known about the effect of interventions aimed at preventing progression from prediabetes to diabetes on glucagon concentrations. We examined the effects of dapagliflozin, metformin or exercise on plasma glucagon concentration in individuals with HbA1c-defined prediabetes. Methods: 120 individuals were randomized to a 13-week intervention with dapagliflozin (10 mg once daily), metformin (850 mg twice daily), exercise (interval training 30 min 5 days/week) or control (habitual living). A 75 g oral glucose tolerance test (OGTT; 0, 30, 60 and 120 min) was administered at baseline, at 13 weeks (end of intervention) and at 26 weeks (end of follow-up). Linear mixed-effects models were used to assess effects on fasting concentration, early (0-30 min) area under the curve relative to the fasting level (rAUC0-30 min) and full rAUC0-120 min for glucagon. Results: At baseline, the median (Q1;Q3) age was 62 (54;68) years, HbA1c 5.9% (5.7;6.1%), fasting glucagon 11 (7;15) pmol/L, and 56% were men. No differences in the glucagon measures between groups from baseline to 13 or 26 weeks were observed (Table 1). Conclusions: 13 weeks of treatment with dapagliflozin, metformin or exercise was not associated with changes in fasting or post-OGTT glucagon concentrations in individuals with prediabetes. Disclosure K.K.B. Clemmensen: Research Support; Self; AstraZeneca, Novo Nordisk Foundation. Stock/Shareholder; Spouse/Partner; Novo Nordisk A/S. M.B. Blond: None. H. Amadid: None. L.B. Nielsen: None. D. Vistisen: Stock/Shareholder; Self; Novo Nordisk A/S. K. Karstoft: Employee; Spouse/Partner; Novo Nordisk A/S. F. Persson: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Novo Nordisk A/S. Research Support; Self; Amgen, AstraZeneca, Novo Nordisk A/S. Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Merck Sharp & Dohme Corp., Mundipharma International, Novo Nordisk A/S. M. Ried-Larsen: None. J.J. Holst: Advisory Panel; Self; AstraZeneca, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Zealand Pharma A/S. Other Relationship; Spouse/Partner; Antag Therapeutics. N.J. Wewer Albrechtsen: Research Support; Self; Mercodia, Novo Nordisk A/S, Novo Nordisk Foundation. Speaker’s Bureau; Self; Merck Sharp & Dohme Corp. S.S. Torekov: Research Support; Self; Novo Nordisk Inc. J.S. Quist: None. M.E. Jørgensen: Research Support; Self; Amgen, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Sanofi-Aventis. Stock/Shareholder; Self; Novo Nordisk A/S. K. Færch: None. Funding Novo Nordisk Foundation; AstraZeneca; University of Copenhagen; Innovation Foundation