Introduction: Safety, adherence and treatment satisfaction to interventions with dapagliflozin, metformin or exercise in individuals with prediabetes defined by the HbA1c criterion were studied in the randomized controlled PRE-D trial.

Methods: 120 participants were randomized 1:1:1:1 to 13 weeks of either: (1) dapagliflozin (DAP, 10 mg daily); (2) metformin (MET, 1700 mg daily); (3) exercise (EXE, 5x30 min/week); or (4) control (CON, no treatment). Adverse events (AE) were collected during the entire study. Satisfaction with the interventions was assessed at 6 and 13 weeks using questionnaires. Adherence was assessed at 6 and 13 weeks by pill count in DAP and MET and each week by uploaded training data in EXE. Comparisons between groups were performed by ANOVA and chi-square tests.

Results: At baseline, the median (Q1;Q3) HbA1c was 41 (39;43) mmol/mol (5.9 (5.7;6.1)%); age 62 (54;68) years, and 44% were men. Drop outs were 2 in DAP, 1 in MET, 3 in EXE and 2 in CON. One serious AE occurred in CON (cancer). 40% of the participants experienced at least one AE during the trial (15 in DAP, 22 in MET, 7 in EXE and 4 in CON (DAP vs. MET: P=0.111; MET vs. EXE: P<0.001)). Most AEs were known side-effects of the two medications; urogenital symptoms in DAP, and gastrointestinal symptoms in MET. In all groups, median (Q1;Q3) adherence was high (DAP 100.0 (97.7;100.4)%; MET 96.0 (91.4;98.3)%; EXE 95.9 (89.9;103.2)% (session duration) and 94.5 (90.3;101.1)% (session completion)). Almost all participants in the EXE group were satisfied with their allocated intervention, while this was only true for half of the participants in the CON, DAP and MET groups. Most participants would have preferred allocation to the EXE intervention.

Conclusion: In individuals with prediabetes, treatment with DAP is safe and did not result in more side-effects than treatment with MET. Adherence to all interventions was high, although the most preferred intervention was the EXE intervention.


H. Amadid: None. M.B. Blond: None. L. Bruhn: None. K.K. Clemmensen: None. C.T. Vainø: None. F. Persson: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Novo Nordisk A/S. Research Support; Self; AstraZeneca, Sanofi. Speaker's Bureau; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi. M.E. Jørgensen: Research Support; Self; Amgen Inc., AstraZeneca, Danish Diabetes Association, Sanofi-Aventis. Stock/Shareholder; Self; Novo Nordisk A/S. K. Færch: Research Support; Self; Ascensia Diabetes Care, AstraZeneca, Unilever. Stock/Shareholder; Self; Novo Nordisk A/S.

Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at