Type 2 Diabetes: Think Twice Before Switching to Sulfonylureas
Guidelines have long recommended metformin as a first-line treatment for type 2 diabetes, but patients with an intolerance to metformin or for whom metformin cannot sufficiently control blood glucose levels may sometimes need to add or switch to a second-line therapy.
Sulfonylureas are the most common second-line treatments for type 2 diabetes, but these drugs come with various risks, according to Antonios Douros, MD, PhD, postdoctoral scholar in the Department of Epidemiology, Biostatistics, and Occupational Health at McGill University in Montreal, Quebec, Canada.
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In a new study, Dr Douros and colleagues found that adding or switching to sulfonylureas was associated with increased risks of myocardial infarction, hypoglycemia, and all-cause mortality compared with continuing metformin monotherapy in patients with type 2 diabetes.1
Moreover, compared with adding sulfonylureas, switching to sulfonylureas was associated with increased risks of myocardial infarction and all-cause mortality. Thus, adding sulfonylureas to first-line metformin treatment is likely be a safer option than switching to sulfonylureas entirely in this patient population.
Consultant360 spoke with Dr Douros about these findings, their implications for clinical practice, and second-line alternatives to sulfonylureas.
Consultant360: How did your study come about? Why did you decide to compare the effects of continuing metformin monotherapy vs adding sulfonylureas to metformin or switching to sulfonylureas entirely?
Antonios Douros: Despite the fact that several new antidiabetic drug classes were approved in the last years, sulfonylureas have remained the most commonly used second-line drugs in type 2 diabetes. With this in mind, our primary analysis in our study was to assess how switching entirely to sulfonylureas or adding sulfonylureas to current metformin monotherapy compares with continuing metformin monotherapy.
Ultimately, our study demonstrated increased risks of myocardial infarction, all-cause mortality, and severe hypoglycemia in patients who added or switched entirely to sulfonylureas.
In a secondary analysis, we compared outcomes among patients that added sulfonylureas to current metformin treatment with patients that switched entirely from metformin to sulfonylureas. Our results showed that continuing metformin is likely a better option than switching completely to sulfonylureas.
C360: As you mentioned earlier, your study found that switching to sulfonylureas entirely was associated with several serious health risks compared with continuing metformin. Why do you think this was the case?
AD: I think there could be 2 reasons. First, there have been concerns about the cardiovascular safety of sulfonylureas at least since the 1970s. For a long time, we have suspected that sulfonylureas could be associated with adverse cardiovascular outcomes, and the results of our study corroborate these concerns.
Second, metformin treatment is probably cardio-protective. Our hypothesis and potential explanation for our findings is that metformin may be able to compensate for the increased cardiovascular risks of sulfonylureas.
C360: What would you recommend to a clinician who is treating a patient with type 2 diabetes and is caught between these two treatment decisions? What factors should they consider in their decision-making?
AD: As shown in our study, continuing metformin is probably better than switching entirely to sulfonylureas, but a common reason for cessation of metformin therapy is gastrointestinal disturbances like abdominal pain and discomfort or diarrhea. When patients have concerns about these abdominal disturbances, clinicians will often stop metformin and switch their patients to another drug. However, simply lowering the dose of metformin can sometimes help alleviate these symptoms.
So, a possible recommendation is to keep patients on metformin for as long as possible, and in patients with increased cardiovascular risk, maybe consider other second-line treatments instead of sulfonylureas.
C360: What other second-line treatments might clinicians consider instead of sulfonylureas?
AD: Sulfonylureas are not the only type of second-line treatment that we could use. Nowadays, we have several possibilities. In current guidelines, the American Diabetes Association and most scientific societies around the world have listed several other drug classes as possible second-line treatments.2 These could include dipeptidyl peptidase-4 (DPP-4) inhibitors, glucose-like peptide-1 (GLP-1) receptor agonists, and sodium-glucose co-transporter-2 (SGLT-2) inhibitors.
C360: With the findings from your study in mind, what are the next steps in your research?
AD: One limitation of our study was the short follow-up period. We had a mean follow-up of 1 year. Assessing the long-term risks of sulfonylureas could be a possible research goal for the future. In addition, there is still some work to do with respect to the comparative safety of sulfonylureas and other second-line treatments like DPP-4 inhibitors, GLP-1 receptor agonists, and SGLT-2 inhibitors.
For our coverage of Dr Douros’s study, click here.
—Christina Vogt
References:
- Douros A, Dell’Aniello S, Yu OHY, Filion KB, Azoulay L, Suissa S. Sulfonylureas as second line drugs in type 2 diabetes and the risk of cardiovascular and hypoglycemic events: population based cohort study [Published online July 18, 2018]. BMJ. https://doi.org/10.1136/bmj.k2693
- American Diabetes Association. Classification and diagnosis of diabetes: Standards of Medical Care in Diabetes- 2018. Diabetes Care. 2018;41(Suppl. 1). https://diabetesed.net/wp-content/uploads/2017/12/2018-ADA-Standards-of-Care.pdf