A new study published in The BMJ finds that for the patients with type 2 diabetes (T2D), switching to sulfonylureas as second-line drugs is associated with increased risk of complications (all-cause mortality, severe hypoglycemia, and myocardial infarction) compared to continuing with metformin alone. The researchers say the continuing with metformin while introducing sulfonylureas is safer than switching.
Samy Suissa, professor, McGill University, Montréal, QC, Canada, and colleagues conducted the study to determine whether the addition or switching to sulfonylureas is associated with an increased risk of ischaemic stroke, cardiovascular death, myocardial infarction, severe hypoglycemia, and all-cause mortality, compared with T2D patients remaining on metformin monotherapy.
Metformin is used as the first-line therapy for the treatment of patients with T2D. And, the most commonly recommended second-line treatment is sulfonylureas, often used in combination with metformin.
There has been an extensive study on the safety of sulfonylureas with respect to adverse hypoglycemic and cardiovascular events. However, there is limited data on their cardiovascular and hypoglycaemic safety as a second line drug in patients with poorly controlled diabetes that are in need of adding or switching to other drugs.
For the study, data analysis of over 77,000 patients (average age 64 years) with T2D who started metformin treatment between 1998 and 2013 was done from the UK Clinical Practice Research Datalink. Identification of the patients who subsequently added or switched to a sulfonylurea was done and matched to a similar patient who continued on metformin alone. Admissions for heart attack and ischaemic stroke, cardiovascular death, all-cause mortality, and severe hypoglycemia were then monitored using the hospital records.
- During an average follow-up period of just over a year, sulfonylurea use (switching and adding combined) was associated with an increased risk of heart attack (7.8 v 6.2 per 1000 person-years), all-cause mortality (27.3 v 21.5), and severe hypoglycaemia (5.5 v 0.7), compared with continuing metformin alone.
- There was also a trend towards increased risks of ischaemic stroke (6.7 v 5.5 per 1000 person-years) and cardiovascular death (9.4 v 8.1) with sulfonylurea use.
- Compared with adding sulfonylureas to metformin treatment, switching to sulfonylureas was associated with a greater risk of heart attack and all-cause mortality, but no differences were found for ischaemic stroke, cardiovascular death, or severe hypoglycemia.
Findings remained similar after further analyses to test the strength of the results.
This is an observational study, so cause and effect cannot be established. “The possibility that some of the observed risks may be due to other unmeasured (confounding) factors cannot be ruled out, researchers note. Nevertheless, the results are highly generalizable and the large sample size allowed the calculation of precise estimates.”
Based on the study, the researchers conclude that sulfonylureas as second-line drugs are associated with an increased risk of all-cause mortality, severe hypoglycemia, and myocardial infarction compared with remaining on metformin monotherapy. Continuing with metformin when introducing sulfonylureas appears to be safer than switching.
For more information follow the link: https://doi.org/10.1136/bmj.k2693