Increased Frequency of Severe Hypoglycemia with the Modified-Release Gliclazide Compared to Glimepiride in Diabetic Older Adults; Propensity Score-Adjusted Analysis

OBJECTIVE: The main aim is to compare the risk of severe hypoglycemia associated with the modified-release (MR) gliclazide against glimepiride in diabetic older adults. METHODS: All older adult diabetic patients who attended the emergency department (ED) between the 1st of Aug. 2017 and the end of Mar 2020 on gliclazide MR or glimepiride are included in two cohorts. We compared baseline differences between cohorts in demographics, lab results, diabetes complications, comorbidities, and drugs using the chi-squared test for categorical variables and unpaired t-test for continuous variables. All the baseline variables are used in a logistic regression to produce the propensity scores for receiving gliclazide MR. The primary outcome was Severe Hypoglycemia requiring Emergency Admission (SHEA). We used documented hypoglycemia, falls, fractures, Cardiovascular ED Admission (CVEA), and recurrent ED admissions as secondary outcomes. We used a univariate logistic regression followed by a propensity score-adjusted logistic regression to identify the adjusted odds ratio. We did a subgroup analysis for low and moderate-high doses users. RESULTS: We included 2320 patients, 1786 were on gliclazide MR while 534 were on glimepiride. The risk of SHEA (Adjusted Odds Ratio AOR 6.74, p=0.002), falls (AOR 1.43, p=0.003), fractures (AOR 1.43, p=0.01), CVEA (AOR 1.66, p<0.001), recurrent ED admission (AOR 1.39, p=0.002) were significantly higher. At the same time, documented hypoglycemia was insignificantly higher (AOR 1.17, p= 0.444) with gliclazide MR compared to glimepiride. The low doses of both treatments did not show any SHEA cases, while the results with higher doses showed the same pattern of increased risk with gliclazide MR as the principle analysis. CONCLUSION: Using gliclazide MR for older patients may not be a relatively safer alternative to avoid severe hypoglycemia and its possible consequences compared to glimepiride. It may be added to glimepiride in the Beers list of medications to be avoided in older adults.