DURATION-8 Randomized Controlled Trial 104-Week Results—Once-Weekly Exenatide (ExQW) plus Once-Daily Dapagliflozin (DAPA) vs. ExQW or DAPA Alone

In patients with T2D uncontrolled on metformin alone, ExQW + DAPA significantly reduced glycemia, body weight and systolic blood pressure compared to ExQW + placebo (PBO) or DAPA + PBO at 28 weeks (NCT02229396). Here, we examined efficacy and safety after 104 weeks of double-blind therapy. Of 695 patients randomized, 431 (62%) completed 104 weeks; 4.3% withdrew due to adverse events (AEs). Absolute reductions and between-group differences in A1C were maintained over 104 weeks (Figure). Clinically relevant changes vs. baseline in other efficacy end points were also observed (Table). AEs and serious AEs were balanced across treatment groups. Hypoglycemia incidence was low (Table). In conclusion, ExQW + DAPA maintained efficacy over 104 weeks with no unexpected safety concerns.Changes in efficacy end points and hypoglycemia incidence from baseline through week 104ExQW+DAPA N=228 n=147ExQW+PBO N=227 n=132DAPA+PBO N=230 n=152ExQW+DAPA vs ExQW+PBOExQW+DAPA vs DAPA+PBOA1C, % BL mean (SD) 28 wk LSM change from BL (SE) 52 wk LSM change from BL (SE) 104 wk LSM change from BL (SE)□ 9.29 (1.06) −1.98 (0.09) −1.75 (0.10) −1.70 (0.11)□ 9.26 (1.08) −1.60 (0.10) −1.38 (0.10) −1.29 (0.12)□ 9.25 (1.02) −1.39 (0.09) −1.23 (0.10) −1.06 (0.12)□ □ −0.38 (0.13)** −0.37 (0.14)** −0.42 (0.15)**□ □ −0.59 (0.13)*** −0.52 (0.13)*** −0.64 (0.15)***FPG, mg/dL BL mean (SD) 28 wk LSM change from BL (SE) 52 wk LSM change from BL (SE) 104 wk LSM change from BL (SE)□ 195.0 (53.5) −65.8 (2.9) −63.0 (2.9) −49.0 (4.1)□ 189.3 (49.8) −45.8 (3.0) −45.4 (3.1) −29.8 (4.5)□ 188.5 (44.2) −49.2 (2.9) −39.8 (3.0) −21.9 (4.6)□ □ −20.1 (4.0)*** −17.6 (4.1)*** −19.2 (5.9)***□ □ −16.6 (3.9)*** −23.3 (4.0)*** −27.1 (6.0)***2h-PPG, mg/dL BL mean (SD) 28 wk LSM change from BL (SE) 52 wk LSM change from BL (SE) 104 wk LSM change from BL (SE)□ 268.5 (67.5) −87.8 (4.1) −82.4 (4.8) −86.2 (5.9)□ 266.1 (67.2) −60.1 (4.3) −64.0 (5.1) −79.0 (7.0)□ 261.5 (60.2) −61.1 (4.1) −59.6 (5.0) −64.0 (6.6)□ □ −27.7 (5.2)*** −18.4 (6.3)** −7.2 (7.9)□ □ −26.8 (5.1)*** −22.8 (6.2)*** −22.2 (7.9)**Body weight, kg BL mean (SD) 28 wk LSM change from BL (SE) 52 wk LSM change from BL (SE) 104 wk LSM change from BL (SE)□ 92.1 (21.8) −3.6 (0.3) −3.3 (0.4) −2.5 (0.4)□ 89.1 (18.7) −1.6 (0.3) −1.5 (0.4) −0.8 (0.5)□ 90.9 (19.6) −2.2 (0.3) −2.3 (0.4) −3.0 (0.5)□ □ −2.0 (0.4)*** −1.8 (0.5)*** −1.7 (0.6)**□ □ −1.3 (0.4)*** −1.0 (0.5) +0.5 (0.6)Systolic BP, mmHg BL mean (SD) 28 wk LSM change from BL (SE) 52 wk LSM change from BL (SE) 104 wk LSM change from BL (SE)□ 130.7 (12.1) −4.3 (0.8) −4.5 (0.8) −3.1 (1.0)□ 129.3 (12.5) −1.2 (0.8) −0.7 (0.9) −0.1 (1.1)□ 129.6 (12.8) −1.8 (0.8) −2.7 (0.8) −1.1 (1.0)□ □ −3.0 (1.1)** −3.9 (1.1)*** −3.0 (1.4)*□ □ −2.4 (1.1)* −1.8 (1.1) −2.0 (1.4)Hypoglycemia† through 104 wks Major, % pts Minor, % pts Other, % ptsN=231 0 1.7 6.9N=230 0 0 3.5N=233 0 0.4 3.4*P<0.05, **P<0.01, ***P≤0.001 (P-values at wk 52 and wk 104 are nominal). BL, baseline, BP, blood pressure; FPG, fasting plasma glucose; LSM, least-squares mean; N, number comprising the intention-to-treat analysis set; n, number completing 104 weeks of treatment; 2h-PPG, 2-hour post-prandial glucose; pts, patients; SD, standard deviation; SE, standard error; wk, week. †Major hypoglycemia: loss of consciousness, seizure or coma resolving after glucagon or glucose administration or events requiring third-party assistance due to severe impairment of consciousness or behavior with blood glucose concentration <54 mg/dL. Minor hypoglycemia: non-major event with symptoms consistent with hypoglycemia and blood glucose concentration <54 mg/dL. Other hypoglycemia: events not meeting major or minor hypoglycemia criteria. Disclosure S. Jabbour: None. C. Guja: Consultant; Self; AstraZeneca, Bayer AG, Eli Lilly and Company, Merck KGaA, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi, Boehringer Ingelheim GmbH. E. Hardy: Employee; Self; AstraZeneca. Stock/Shareholder; Self; AstraZeneca. S. Bhattacharya: None. P.K. Ohman: Employee; Self; AstraZeneca. J.P. Frias: Research Support; Self; AbbVie Inc., Allergan, Amgen Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Bristol-Myers Squibb Company. Consultant; Self; CeQur Corporation. Research Support; Self; Cirius Therapeutics, AstraZeneca, Calibra Medical, Elcelyx Therapeutics, Inc.. Consultant; Self; Elcelyx Therapeutics, Inc.. Research Support; Self; Eli Lilly and Company, Genentech, Inc., Ionis Pharmaceuticals, Inc., ICON plc., Janssen Pharmaceuticals, Inc.. Consultant; Self; Johnson & Johnson Diabetes Institute, LLC.. Research Support; Self; Lexicon Pharmaceuticals, Inc., Ligand Pharmaceuticals, Inc.. Consultant; Self; Ligand Pharmaceuticals, Inc.. Research Support; Self; Merck & Co., Inc., Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., Pfizer Inc., Sanofi. Consultant; Self; Sanofi. Speaker's Bureau; Self; Sanofi. Research Support; Self; Theracos, Inc..