Real world efficacy and safety of empagliflozin in Malaysian type 2 diabetes mellitus patients

Background: The empagliflozin clinical trial program (EMPA-REG) demonstrated reductions in glucose, weight, blood pressure (BP) and insulin requirements in type 2 diabetes (T2DM) patients. In Malaysia, real world outcomes data on empagliflozin has not been published. Aim: To assess the real world efficacy and safety of empagliflozin in Malaysian T2DM patients.Method: This study was conducted at the University of Malaya Medical Centre, a tertiary referral hospital in Kuala Lumpur, Malaysia. Empagliflozin prescription data from March to September 2016 was extracted from outpatient records. Demographic details, HbA1c, weight, BP, glomerular filtration rate (GFR), lipids, insulin use, history of cardiovascular disease (CVD) and adverse events were analysed. Patients that did not return for follow-up or had incomplete data were excluded from the analysis.Results: Of the 233 patients identified, 27 were excluded. Empagliflozin was prescribed by endocrinologists (81%), cardiologists (15%) and nephrologists (4%) with a mean follow-up of 19 weeks. Median dose was 25mg daily. 36% of patients had established CVD. At baseline, mean HbA1c was 8.76%, mean weight 79.92kg and mean BP 137/77mmHg. Mean changes from baseline were reductions in HbA1c (-0.71%), weight (-1.60kg) and systolic BP (-3.6mmHg). HbA1c reduction was highest (-1.82%) in those with baseline HbA1c > 10% (Table 1). Weight reduction was highest (-3.97kg) in those with baseline weight above 100 kg (Table 1). BP reduction was highest (-23.4/-7.6mmHg) in those with baseline SBP above 160mmHg (Table 1). Patients who were on insulin at baseline (n = 125, mean baseline HbA1c 9.16%) showed improvements (HbA1c: -0.66%; weight: -1.05 kg) on a stable insulin dose. GFR and LDL-C did not change significantly (-2.33 ml/min and 0.03 mmol/L respectively). The most common adverse event was hypoglycaemia (n = 22), mostly in patients on concomitant sulfonylurea/insulin. Other adverse events were rare: polyuria (n = 3), dehydration (n = 2), postural hypotension (n = 2), urinary tract infection (n = 2), genital tract infection (n = 1) and diarrhoea (n = 1). Discussion: The results of this real world study closely reflect those from the EMPA-REG trials. The majority of patients in this study had sub-optimal glycaemic control and obesity with clinically significant HbA1c, weight and BP reductions of similar magnitudes to those seen in the EMPA-REG trials. The mean follow-up of 19 weeks in our study was comparable to that of the EMPA-REG Multiple Daily Insulin trial. Empagliflozin was particularly effective for patients who were overweight or obese and had an insulin sparing effect. The drug was safe and well tolerated. The most common adverse event was hypoglycaemia, mostly attributable to insulin, highlighting the need for insulin dose reduction on initiation of the drug.