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Exenatide-dapagliflozin efficacy for T2D persists for 2 years

Elvira Manzano
06 Jul 2018

Combined treatment with the GLP-1 receptor agonist exenatide and the SGLT-2 inhibitor dapagliflozin appeared to be effective up to 2 years in patients with type 2 diabetes (T2D), the phase III DURATION-8 extension trial has shown.

“The result was not unexpected,” said lead investigator Dr Serge Jabbour from the Thomas Jefferson University in Philadelphia, US. “Long-term studies of exenatide once-weekly have demonstrated sustained glycaemic improvement, weight reduction, and improved markers of cardiovascular risk, even up to 7 years of treatment. Similar durability has been observed in long-term studies of dapagliflozin in T2D.”

At 104 weeks of treatment, HbA1c reduction from once-weekly exenatide and once-daily dapagliflozin persisted. The exenatide-dapagliflozin combination therapy resulted in a significantly lower mean reduction of HbA1c percentage points from baseline compared with exenatide or dapagliflozin monotherapy (-1.7 vs -1.29 and -1.06, respectively; p<0.01). [ADA 2018, abstract 104-LB]

Fasting plasma glucose levels and 2-hour postprandial glucose, which are clinical markers of glucose control, also improved with combination treatment (FPG, -49 mg/dL vs -29.8 mg/dL for exenatide alone and -21.9 for dapagliflozin alone and PPG, 86.2 mg/dL vs -79.0 mg/dL and -64.0 mg/dL, respectively) and were maintained across the study period.

Who should be on exenatide-dapagliflozin combo

The combination strategy, Jabour said, may work well for patients with uncontrolled HbA1c of ≥9 percent despite being on metformin maximum tolerated dose. “Exenatide-dapagliflozin combination may help patients get closer to a goal.” Alternatively, either agent can be used sequentially, if not at the same time as an adjunct therapy.

The DURATION-8 extension trial included 431 patients who completed 104 weeks of treatment with exenatide and dapagliflozin. All patients had an HbA1c of ≥8 percent and were on a background therapy of a maximum daily dose of metformin 1,500 mg.

Patients on the exenatide-dapagliflozin treatment were given subcutaneous injections of exenatide 2 mg once weekly and oral dapagliflozin 10 mg daily. Those on exenatide or dapagliflozin alone received the same doses. Rescue therapy of basal insulin was allowed as needed.

Weight loss expected with dapagliflozin

As expected, patients on dapagliflozin experienced weight loss, but not those on exenatide alone. In addition, patients on combination treatment had improvement in systolic blood pressure (-3.1 mm Hg) over 104 weeks greater than with dapagliflozin or exenatide alone.

There was a slightly higher percentage of minor events occurring with the combination treatment at 1.7 percent vs 0 percent with exenatide and 0.4 percent with dapagliflozin alone, but the differences were not statistically significant. Overall, exenatide-dapagliflozin combination therapy was well tolerated, Jabour said. There were no new safety signals and the safety profile was consistent with what was expected from each individual agent.

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Most Read Articles
15 Sep 2018
Prenatal and postpartum vitamin D supplementation does not appear to improve foetal or infant growth, a study reports.
Tristan Manalac, 3 days ago
The causes, presentations and management of anaphylaxis vary considerably with age, according to a recent Singapore study, which reported that children are more likely to present with food anaphylaxis, while drug anaphylaxis is more common in adults.
Pearl Toh, 2 days ago
Low-density lipoprotein cholesterol (LDL-C) levels remained high in many patients with stable or acute coronary heart disease (CHD) in Asia, despite having a very high risk of recurrent cardiovascular (CV) events, indicating that the use of lipid-lowering therapies and lipid monitoring were inadequate.
13 Sep 2018
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