Appropriate SGLT2i use can help prevent serious AEs
The appropriate use of sodium/glucose cotransporter 2 inhibitors (SGLT2i) may prevent serious adverse events (SAEs) among Japanese patients with type 2 diabetes (T2D), according to a retrospective analysis of data from medical claim database presented at APSC 2018.
There have been numerous reports of SAEs among Japanese patients receiving SGLT2i despite previous evidence demonstrating the safety of SGLT2i. [Expert Opin Drug Saf 2015;14:795-800] Given these concerns, the Japan Diabetes Society and Japan Association for Diabetes Education and Care outlined recommendations for appropriate SGLT2i use, said lead author Dr Daisuke Yabe from Kansai Electric Power Medical Research Institute, Kobe, Japan.
The recommendations define appropriate use as paying careful consideration to SGLT2i use when combined with insulin (reduced dose) or when used in elderly patients (<65 years). Immediate withdrawal once skin symptoms, fever, or diarrhoea manifest, and urogenital consultations and screening are also recommended. These also highlighted the importance of patient education on hypoglycaemia and measures to counter dehydration (ie, avoidance of diuretics while using SGLT2i). [Expert Opin Drug Saf 2015;14:795-800]
After the recommendations for appropriate use of SGLT2i have been released, the incidence rate of vascular complications such as as myocardial infarction (MI) and cerebral infarction significantly decreased compared with the rates prior to the announcement (1,934.3 vs 2,885.6 and 4,956.7 vs 6,801.8 cases per 105 patient-year, respectively).
Safety of SGLT2i vs other antidiabetics
Using data from the Japan Medical Data Centre Claims database between 2009 and 2013, the researchers conducted a retrospective cohort study involving patients with T2D (aged <75 years) who had at least one ICD-10 code of E11 (n=27,962) or E14 (n=93,280) at the time of analysis. Participants were prescribed SGLT2i or other antidiabetic drugs such as metformin, dipeptidyl peptidase-4 inhibitors (DPP-4i), 𝛼-glycosidase inhibitor, glinide, and thiazolidine. [APSC 2018, abstract S008-01]
By Cox proportional-hazards analysis, patients on SGLT2i showed no significant increased risk of acute MI and cerebral infarction for all events (hazard ratio [HR], 1.3; p=0.6868 and HR, 1.0; p=0.9488) and hospitalized events (HR, 1.7; p=0.5851 and HR, 0.6; p=0.6145) compared with other antidiabetic drugs.
“We could safely say that by using the appropriate way, this [SGLT2i] drug did not do much harm in the clinical setting,” said Yabe.
However, a significantly higher risk of urinary tract infection (HR, 1.4; p=0.0122 for all events and HR, 1.2; p=0.7515 for hospitalized events) and genital infection (HR, 2.5; p<0.0001 for all events) was observed in patients who had SGLT2i compared with other antidiabetic drugs.
Additionally, an episode of euglycaemic diabetic ketoacidosis was observed in a Japanese patient who was on SGLT2i during a strict low-carbohydrate diet. [J Diabetes Investig 2015;6:587-590] “This is partly due to restriction of carbohydrate ingestion. Caution should be paid to patients’ dietary habits when prescribing SGLT2i,” said Yabe.
A previous study, which uses data from a large US medical claims database, reported that patients who were treated with SGLT2i had a twofold higher risk of diabetic ketoacidosis compared with those on DPP-4i. [N Engl J Med 2017;376:2300-2302]“Big data analysis provides very important suggestions, which [suggest how] we can create the recommendations … to improve our diabetes care. Yet, it is critical to see and listen to patients carefully, and try to provide tailored-diabetes care based on what we learn from big data analysis,” Yabe said. “[Furthermore], patient education on SGLT2i-associated genital and urinary tract infection is critical to avoid serious conditions.”