Empagliflozin in combination with oral agents in young and overweight/obese Type 2 diabetes mellitus patients: A pooled analysis of three randomized trials

Romera I, Gomis R, Crowe S, et al.
J Diabetes Complications.2016; published online ahead of print

Background

The percentage of overweight individuals under 65 with type 2 diabetes mellitus (T2DM) and poor blood glucose control is rising. The combination of poor blood glucose control, BMI > 25 kg/m² and younger age, exposes these individuals to increased hyperglycaemic states and a higher risk of long-term complications [1,2].
Sodium-glucose cotransporter 2 (SGLT2) inhibitors inhibit renal glucose reabsorption and minimise excess glucose in the urine, leading to significant HbA1c reductions particularly in overweight/obese patients [3]. Empagliflozin, a SGLT2 inhibitor, is also associated with body weight and systolic blood pressure reductions [4].
In this analysis from three phase 3 studies, the efficacy and safety of empagliflozin was evaluated in 439 T2DM patients younger than 65 years, with BMI 25–35 kg/m² and poorly controlled HbA1c (≥64 mmol/mol), despite diet, exercise and a stable regimen (>12 weeks) of anti-diabetes treatment.

Main results

• Adjusted mean change in HbA1c levels from baseline to week 24 of treatment with empagliflozin 10mg vs. placebo was −0.91% (95%CI: −1.11 to −0.71; P < 0.001) and with empagliflozin 25mg vs. placebo was −0.91% (95%CI: −1.12 to −0.70; P < 0.001).

• The percentage of participants with baseline HbA1c ≥ 64 mmol/mol (8%) achieving a value < 53 mmol/mol (7%) at 24 week was 23.8% vs. 3.6% for empagliflozin 10mg vs. placebo (OR: 8.69; 95% CI: 3.23-23.47; P<0.001)  and 19.9% vs. 3.6% for empagliflozin 25mg vs. placebo (OR: 7.65; 95% CI: 2.77-21.11; P<0.001).

• Adjusted mean change from baseline in body weight reduction at week 24 was −1.61 kg (95%CI: −2.16 to −1.05; P<0.001) for empagliflozin 10mg vs. placebo, and −1.81 kg (95% CI: −2.38 to −1.24; P<0.001) for empagliflozin 25mg vs. placebo.
• No statistically significant differences were seen between empagliflozin and placebo in changes in blood pressure at 24 weeks, with the exception of a lower diastolic blood pressure seen with empagliflozin 25mg vs. placebo (-2.0 mmHg, 95%CI: -3.6 to -0.4, P=0.015).
• Empagliflozin was well tolerated. Overall, adverse effects (AEs) were distributed similarly across treatment groups, except for a higher percentage of confirmed hypoglycaemia AEs with empagliflozin (5.6% and 5.0% for 10 and 25 mg respectively, vs. 3.6% with placebo) and genital infections (3.8% and 5.0% vs 1.4% with placebo).

Conclusion

In T2DM patients younger than 65 years, with BMI 25–35 kg/m² and poorly controlled HbA1c levels (≥64 mmol/mol), the addition of empagliflozin to oral standard therapies was associated with a clinically and statistically significant reduction in HbA1c and in body weight compared to placebo, with a favourable safety profile. These data support an added benefit of the use of empagliflozin on top of standard therapy in this patient group.

Find this article online at J Diabetes Complications

References

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