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Treatment of type 2 diabetes mellitus (T2DM) with glucagon-like peptide-1 receptor agonists (GLP-1RAs) leads to better glycemic control, reduced body weight, and improvement in several cardiovascular risk factors, which has been demonstrated to be accompanied by improved micro- and macrovascular outcomes. However, many patients treated with GLP-1RAs do not reach their glycemic targets, and weight loss achieved with these agents remains well below what can be attained with bariatric surgery. Therefore, there are still opportunities to improve the existing GLP-1RA class.

Coskun et al. describe a novel, single-peptide, dual glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 receptor agonist, LY3298176. The dual functionality of the peptide is described in preclinical in vitro and in vivo models, and clinical assessment demonstrated that administration of LY3298176 led to decreased glucose levels and decreased body weight in healthy individuals during a multiple ascending dose study, and in a randomized, 4-week, Phase 1b trial in T2DM patients.

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