Combination gut hormones: Prospects and questions for the future of obesity and diabetes therapy

Abstract

Obesity represents an important public health challenge for the twenty-first century: Globalised, highly prevalent and increasingly common with time, this condition is likely to reverse some of the hard-won gains in mortality accomplished in previous centuries. In the search for safe and effective therapies for ob esity and its companion, type 2 diabetes mellitus (T2D), the gut hormone glucagon-like peptide-1 (GLP-1) has emerged as a forerunner and analogues thereof are now widely used in treatment of obesity and T2D, bringing proven benefits in improving glycae mia and weight loss and, notably, cardiovascular outcomes. However, GLP-1 alone is subject to limitations in terms of efficacy, and as a result, investigators are evaluati ng other gut hormones such as glucose-dependent insulinotropic peptide (GIP), glucagon and peptide YY (PYY) as possible partner hormones that may complement and enhance GLP-1's therapeutic effects. Such combination gut hormone therapies are in pharmaceu tical development at present and are likely to make it to market within the next few years. This review examines the physiological basis for combination gut hormone therapy and presents the latest clinical results that underpin the excitement around these treatments. We also pose, however, some hard questions for the field which need to b e answered before the full benefit of such treatments can be realised.