Understanding and overcoming metformin gastrointestinal intolerance

Abstract Metformin is the most widely prescribed drug for patients with type 2 diabetes mellitus and the first‐line pharmacologic option as supported by multiple international guidelines, yet a rather large proportion of patients cannot tolerate metformin in adequate amounts because of its associated gastrointestinal (GI) adverse events (AEs). GI AEs typically encountered with metformin therapy include diarrhoea, nausea, flatulence, indigestion, vomiting, and abdominal discomfort, with diarrhoea and nausea being the most common. Although starting at a low dose and titrating slowly may help prevent some of metformin's GI AEs, some patients are unable to tolerate metformin at all and it may also be difficult to convince patients to start metformin again after a bout of GI AEs. Despite this clinical importance the underlying mechanisms of metformin's GI intolerance are poorly known. This review discusses the epidemiology of metformin GI intolerance; its underlying mechanisms; genotype variability and associated factors affecting metformin GI intolerance, such as comorbidities, co‐medications, and bariatric surgery; clinical consequences, and therapeutic strategies to overcome metformin GI intolerance. These strategies include appropriate titration of immediate‐release metformin, use of extended‐release metformin, the promise of delayed‐release metformin and gut microbiome modulators, and alternative pharmacological therapies when metformin cannot be tolerated at all. G...
Source: Diabetes, Obesity and Metabolism - Category: Endocrinology Authors: Tags: REVIEW ARTICLE Source Type: research