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Initial combination therapy with metformin, pioglitazone and exenatide is more effective than sequential add-on therapy in subjects with new-onset diabetes

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However, they address different pathophysiological defects: pioglitazone targets insulin resistance at the tissue level, while GLP-1 agonists target pancreatic beta cell function and satiety

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Less common adverse effects observed in clinical trials include transient increases in heart rate, typically modest and not associated with adverse cardiovascular events in trial populations