Exenatide, dapagliflozin combination improves glycemic control

A combination of the glucagon-like peptide-1 receptor agonist exenatide and the SGLT2 inhibitor dapagliflozin is more effective for improving glycemic control in patients with type 2 diabetes compared with either therapy alone, according to findings presented at the 52nd European Association for the Study of Diabetes Annual Meeting and simultaneously published in The Lancet Diabetes & Endocrinology.

“There is a potential benefit of a GLP-1 receptor agonist and SGLT2 [inhibitor combination] in patients with poor glycemic control with metformin alone; however, their combination in patients with type 2 diabetes with poor glycemic control has not yet been studied in a randomized controlled trial,” Cristian Guja, MD, PhD, diabetologist and professor in the department of diabetes, nutrition and metabolic disease at Carol Davila University of Medicine and Pharmacy in Bucharest, Romania, said during the presentation.

Guja and colleagues evaluated data from the DURATION-8 study on 695 adults (mean age, 54 years) with type 2 diabetes and inadequate glycemic control (HbA1c, 8%-12%) despite stable metformin monotherapy randomly assigned to once-weekly subcutaneous injection exenatide (Bydureon, AstraZeneca) 2 mg plus once-daily dapagliflozin (Farxiga, AstraZeneca; n = 231) 10 mg oral tablets, exenatide alone (n = 231) or dapagliflozin alone (n = 233) between Sept. 4, 2014, and Oct. 15, 2015.

“The aim of DURATION-8 was to compare the antihyperglycemic and metabolic efficacy and safety of combining weekly exenatide and dapagliflozin vs. exenatide alone or dapagliflozin alone in patients with type 2 diabetes with poor control on metformin monotherapy,” Guja said.

Participants in all three treatment groups had improved HbA1c from baseline to week 28. Participants in the combination group had the greatest decrease: 2% compared with 1.4% in the dapagliflozin-alone group (P < .001) and 1.6% in the exenatide-alone group (P = .004).

Fasting plasma glucose also decreased more in the combination group (3.6 mmol/L) compared with the exenatide-alone group (2.5 mmol/L; P < .001) or the dapagliflozin-alone group (2.7 mmol/L; P < .001).

At week 28, the decrease in postprandial plasma glucose was greater in the combination group (4.8 mmol/L) compared with the exenatide-alone group (3.3 mmol/L; P < .001) or dapagliflozin-alone group (3.4 mmol/L; P < .001).

The highest weight loss was recorded in the combination group at week 28 (–3.4 kg) compared with the exenatide-alone group (–1.5 kg; P < .001) or dapagliflozin-alone group (–2.2 kg; P = .002). Starting from a baseline systolic blood pressure of 130 mm Hg, the combination group exhibited decreased systolic BP by 4.2 mm Hg compared with the exenatide-alone group (1.3 mm Hg; P = .007) and the dapagliflozin-alone group (1.8 mm Hg; P = .025).

No significant differences were found between the groups for adverse events, serious adverse events, including death, and any adverse events leading to treatment discontinuation.

“The concomitant addition of weekly exenatide and dapagliflozin in patients with poor glycemic control on metformin alone was associated with a significantly greater reduction than with either individual therapy in glycemic parameters, including HbA1c, FPG and 2-hour postprandial glucose, [and] significantly higher reductions in weight and systolic BP,” Guja said. “There were no new safety signals, and the safety profile was consistent with that expected from each individual agent. Overall, these findings support the efficacy and safety of co-initiating exenatide and dapagliflozin in patients with type 2 diabetes inadequately controlled on metformin monotherapy.” – by Amber Cox

Reference s :

Frías JP, et al. Lancet Diabetes Endocrinol. 2016;doi:10.1016/S2213-8587(16)30267-4.

Guja C, et al. DURATION-8 study: dapagliflozin and exenatide QW combination. Presented at: 52nd EASD Annual Meeting; Sept. 12-16, 2016; Munich.

Disclosure: The study was funded by AstraZeneca. Guja reports various financial ties with Alfa Wasserman, AstraZeneca, Bayer, Berlin-Chemie/Menarini, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Merck, Merck Sharp and Dohme, Novartis, Novo Nordisk, Sanofi, Servier Pharma and Worwag Pharma.