What is Risk of Hypoglycemia When Adding Sulphonylurea to Metformin for Diabetes Control?

MedicalResearch.com Interview with:

Stig Ejdrup Andersen MD, PhD Clinical Pharmacology Unit Zealand University Hospital Roskilde Denmark

Dr. Andersen

Stig Ejdrup Andersen MD, PhD
Clinical Pharmacology Unit
Zealand University Hospital
Roskilde Denmark

MedicalResearch.com: What is the background for this study?

Response: For decades, we have used sulphonylurea derivates in the medical treatment of type 2 diabetes. Although several newer drugs have become available, adding an SU is still a recommended and acceptable strategy when metformin monotherapy fails. The SUs are among the cheapest glucose lowering drugs on the marked but the risk of hypoglycaemia make clinicians prefer a newer oral drug such as a DPP-IV inhibitor or a SGLT-2 inhibitor to ansulphonylurea because even mild hypoglycaemia may affect the patients’ quality of life negatively.

Several meta-analyses have examined the effectiveness and safety of noninsulin antidiabetic drug, all of which have considered the SUs a homogenous drug class. Pharmacologically, however, the SU agents are quite different. In 2004, a randomized controlled trial by Shernthaner et al. indicated that in comparison with glimepiride, gliclazide MR is equally effective and is associated with fewer hypoglycaemic episodes. Still, head-to-head comparisons of the SU-agents as add-on to metformin are few. In the absence of robust designed comparative trials, we decided to compare the relative risk of hypoglycaemia among the newer SU-agents in a network meta-analysis.

MedicalResearch.com: What are the main findings?

Response: We compared four  sulphonylureas (gliclazide, glipizide, glibenclamide (glyburide) and glimepiride) in our study and found that the risk of hypoglycaemia of any severity differed among these drugs with gliclazide having the lowest risk. Only the risk of hypoglycaemia associated with glipizide, however, was statistically higher than the risk with gliclazide.

Furthermore, the risk of hypoglycaemia with gliclazide was not statistically different from that of the other oral non-SU-agents included in our study with the exception of pioglitazone.

Additionally, our meta-analysis supports that the sulphonylureas and the non-SU-agents are equally effective in reducing in HbA1C and that SU-treatment is associated with weight gain.

MedicalResearch.com: What should readers take away from your report?

Response: The risk of hypoglycaemia does not seem to pertain to sulphonylureas as a drug class. We hope that these results can assist the clinicians when choosing between the new SUs. It is important to emphasize that the selection of a glucose lowering drug should always be individualied and respect the patients’ choice. Our study indicates that we should not completely opt out of the sulphonylureas even if hypoglycemia is a concern. To many patients, adding gliclazide might still be a rational alternative to the more expensive newer oral glucose lowering when metformin monotherapy fails.

MedicalResearch.com: What recommendations do you have for future research as a result of this study?

Response: Since it remains unclear whether the sulphonylureas possess different risk of severe hypoglycaemia, additional studies are needed to address this question.

Secondly, we do not know yet if the different pharmacological profiles of the  sulphonylureas translate into differences in the ability to prevent diabetic complications and reduce mortality.

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Citation: Hypoglycaemia when Adding Sulphonylurea to Metformin: A Systematic Review and Network Meta-analysis
S. E. Andersen1,* and M. Christensen2
DOI: 10.1111/bcp.13059 British Journal Clinical Pharmacology

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