Safety of injectable semaglutide for type 2 diabetes

Introduction: Semaglutide is the most recently approved injectable glucagon-like peptide-1 receptor agonist (GLP-1RA) for people with type 2 diabetes (T2DM). It is one of the three currently marketed GLP-1RAs that can be administered once weekly.

Areas covered: This review focusses on the safety of injectable semaglutide. Semaglutide has been assessed in the SUSTAIN phase 3 clinical trial programme, which included patients across the disease spectrum, i.e. treatment-naïve to those receiving insulin. The authors have looked at all published literature on safety considerations of once weekly GLP-1RA with particular reference to semaglutide.

Expert opinion: Semaglutide is the most powerful injectable GLP-1RA. The cardiovascular (CV) outcome trial (SUSTAIN 6) showed CV superiority and its adverse event profile is as expected for the GLP-1RA class with predominantly gastrointestinal side-effects. Concerns about the thyroid and pancreatic safety have not been substantiated. There is no indication of renal or liver harm for semaglutide. Data consistent with reno-protection and benefit in liver disease is presented. There is a modest signal for increased gall bladder adverse events. An increase in diabetic retinopathy (DR) events in the SUSTAIN 6 trial is the most concerning safety signal. Caution regarding DR is needed when initiating semaglutide and recommendations are suggested.