Safety outcomes of antidiabetic medications: A comprehensive review of the EU summaries of product characteristics and international clinical practice guidelines.
Information on the safety profile of antidiabetic medications is essential for informed treatment decisions in type 2 diabetes mellitus. Although this information is available in regulatory documents of individual drugs, a comprehensive overview across all approved antidiabetics is lacking. Such an overview is important for clinicians and regulators to compare safety profiles across antidiabetics and to understand how safety information evolves over time.
Safety information for 27 first-in-class antidiabetics approved in the European Union (1995-2024) was extracted from the summary of product characteristics (SmPCs) and three clinical practice guidelines (CPGs: European Association for the Study of Diabetes, American Diabetes Association and National Institute for Health and Care Excellence). We assessed changes in safety outcomes over time, with these classified using the Medical Dictionary for Regulatory Activities (preferred term [PT] level).
A total of 326 unique safety outcomes were identified, with 63 of these also reported in CPGs. The number of safety outcomes increased post-marketing for most classes, notably in SGLT-2 inhibitors (+21 PTs) and GLP-1 RAs (+18 PTs). Hypoglycaemia (96%) and skin reactions (e.g., 59.3% rash) were commonly reported. Less frequent outcomes included genital infections (SGLT-2i) and acute haemolytic anaemia (sulfonylureas). Severe but rare outcomes such as Stevens-Johnson syndrome (DPP-4 inhibitors) and Fournier's gangrene (SGLT-2 inhibitors) were added post-marketing.
The safety profile of antidiabetics is similar, with small divergence including some serious safety outcomes, and has expanded over time by approximately one-third. On the contrary, CPGs incorporated only a few safety outcomes, reflecting their distinctive different role in clinical practice.
Safety information for 27 first-in-class antidiabetics approved in the European Union (1995-2024) was extracted from the summary of product characteristics (SmPCs) and three clinical practice guidelines (CPGs: European Association for the Study of Diabetes, American Diabetes Association and National Institute for Health and Care Excellence). We assessed changes in safety outcomes over time, with these classified using the Medical Dictionary for Regulatory Activities (preferred term [PT] level).
A total of 326 unique safety outcomes were identified, with 63 of these also reported in CPGs. The number of safety outcomes increased post-marketing for most classes, notably in SGLT-2 inhibitors (+21 PTs) and GLP-1 RAs (+18 PTs). Hypoglycaemia (96%) and skin reactions (e.g., 59.3% rash) were commonly reported. Less frequent outcomes included genital infections (SGLT-2i) and acute haemolytic anaemia (sulfonylureas). Severe but rare outcomes such as Stevens-Johnson syndrome (DPP-4 inhibitors) and Fournier's gangrene (SGLT-2 inhibitors) were added post-marketing.
The safety profile of antidiabetics is similar, with small divergence including some serious safety outcomes, and has expanded over time by approximately one-third. On the contrary, CPGs incorporated only a few safety outcomes, reflecting their distinctive different role in clinical practice.
Authors
Liang Liang, Weir Weir, Thevasahayam Thevasahayam, Deneer Deneer, Siebes Siebes, Gardarsdottir Gardarsdottir
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