Empagliflozin: A Review in Type 2 Diabetes
Empagliflozin (Jardiance®), a potent, highly selective, sodium glucose cotransporter-2 (SGLT2) inhibitor, is an effective and generally well tolerated antihyperglycaemic agent approved for the treatment of adults with type 2 diabetes (T2D) in the EU, USA and Japan, among other parts of the world. As with other members of its class, empagliflozin offers the convenience of once-daily oral administration and carries a low inherent risk of hypoglycaemia as a result of its insulin-independent mechanism of action, enabling it to be used as monotherapy and as a component of combination therapy with other antidiabetic agents with complementary modes of action to improve glycaemic control in patients with T2D. Beyond lowering glucose, empagliflozin exerts a favourable effect on a number of nonglycaemic outcomes, including modest reductions in bodyweight and blood pressure. As an adjunct to standard care, it demonstrated cardioprotective and renoprotective properties largely independent of glycaemic control in patients with T2D and established cardiovascular disease (CVD) in a mandated cardiovascular (CV) outcomes trial (EMPA-REG OUTCOME). Empagliflozin is generally well tolerated as monotherapy or as add-on therapy and, unlike canagliflozin (the only other SGLT2 inhibitor that has so far shown CV and renal benefits), it has not been associated with an increased risk of amputation or bone fractures. In conclusion, empagliflozin is a valuable treatment option for the management of T2D. Given its demonstrable cardioprotective benefits, the drug is worthy of preferential consideration in patients at high CV risk who require an (additional) antidiabetic medication in order to attain their glycaemic goal.
During the peer review process, the manufacturer of empagliflozin was also offered an opportunity to review this article. Changes resulting from comments received were made on the basis of scientific and editorial merit.
Compliance with Ethical Standards
The preparation of this review was not supported by any external funding.
Conflict of interest
James Frampton is a salaried employee of Adis/Springer, is responsible for the article content and declares no relevant conflicts of interest.
- 2.Inzucchi SE, Bergenstal RM, Buse JB, et al. Management of hyperglycemia in type 2 diabetes, 2015: a patient-centered approach: update to a position statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care. 2015;38(1):140–9.CrossRefPubMedGoogle Scholar
- 6.European Medicines Agency. Jardiance 10 and 25 mg film-coated tablets: summary of product characteristics. 2014. http://www.ema.europa.eu. Accessed 8 June 2018.
- 7.Boehringer Ingelheim Pharmaceuticals, Inc. Jardiance® (empagliflozin) tablets, for oral use. US prescribing information. 2016. http://docs.boehringer-ingelheim.com/Prescribing%20Information/PIs/Jardiance/jardiance.pdf. Accessed 8 June 2018.
- 10.Levine MJ. Empagliflozin for type 2 diabetes mellitus: an overview of phase 3 clinical trials. Curr Diabetes Rev. 2016;12(4):1–19.Google Scholar
- 15.Kovacs CS, Seshiah V, Swallow R, et al. Empagliflozin improves glycaemic and weight control as add-on therapy to pioglitazone or pioglitazone plus metformin in patients with type 2 diabetes: a 24-week, randomized, placebo-controlled trial. Diabetes Obes Metab. 2014;16(2):147–58.CrossRefPubMedGoogle Scholar
- 19.Barnett AH, Mithal A, Manassie J, et al. Efficacy and safety of empagliflozin added to existing antidiabetes treatment in patients with type 2 diabetes and chronic kidney disease: a randomised, double-blind, placebo-controlled trial. Lancet Diabetes Endocrinol. 2014;2(5):369–84.CrossRefPubMedGoogle Scholar
- 21.Rosenstock J, Jelaska A, Frappin G, et al. Improved glucose control with weight loss, lower insulin doses, and no increased hypoglycaemia with empagliflozin added to titrated multiple daily injections of insulin in obese inadequately controlled type 2 diabetes. Diabetes Care. 2014;37:1815–23.CrossRefPubMedGoogle Scholar
- 22.Roden M, Merker L, Christiansen AV, et al. Safety, tolerability and effects on cardiometabolic risk factors of empagliflozin monotherapy in drug-naive patients with type 2 diabetes: a double-blind extension of a phase III randomized controlled trial. Cardiovasc Diabetol. 2015;14:154.CrossRefPubMedPubMedCentralGoogle Scholar
- 25.Kovacs CS, Seshiah V, Merker L, et al. Empagliflozin as add-on therapy to pioglitazone with or without metformin in patients with type 2 diabetes mellitus. Clin Ther. 2015;37(8):1773–88.e1.Google Scholar
- 26.Ridderstrale M, Elsasser U, Zeller C, et al. Influence of baseline HbA1c, BMI, beta-cell function, and insulin sensitivity on the treatment response of empagliflozin (EMPA) in patients with type 2 diabetes (T2DM) [abstract no. 118-LB]. Diabetes. 2015;64(Suppl 1A):LB31.Google Scholar
- 27.Romera I, Ampudia-Blasco FJ, Perez A, et al. Efficacy and safety of empagliflozin in combination with other oral hypoglycemic agents in patients with type 2 diabetes mellitus. Endocrinologia y Nutricion (English Edition). 2016;63(10):519–26.Google Scholar
- 31.EMA. Assessment report. Jardiance. International non-proprietary name: empagliflozin. Procedure No. EMEA/H/C/002677/II/0014. http://www.ema.europa.eu. Accessed 8 June 2018.
- 34.Schnee J, Inzucchi SE, Zinman B, et al. Consistent effect of empagliflozin on composite outcomes related to heart failure: results from EMPA-REG OUTCOME [abstract no. 182]. Diabetologia. 2017;60(Suppl 1):S85–6.Google Scholar
- 35.Fitchett D, Mathieu C, Kaspers S, et al. Empagliflozin (EMPA) reduces mortality in analyses adjusted for control of blood pressure (BP), low density lipoprotein cholesterol (LDL-C) and HbA1c over time [abstract no. 42]. Diabetologia. 2017;60(Suppl 1):S21.Google Scholar
- 36.McKnight J, Fitchett D, Lee J, et al. Empagliflozin (EMPA) reduces heart failure outcomes irrespective of blood pressure (BP), low density lipoprotein cholesterol (LDL-C) and HbA1c control [abstract no. 899]. Diabetologia. 2017;60(1 Suppl 1):S416–7.Google Scholar
- 44.Levin A, Nangaku M, Kadowaki T, et al. Safety and tolerability of empagliflozin in patients with t2d and advanced kidney disease: a large, pooled analysis of placebo-controlled clinical trials (abstract no. 1218-P plus poster). Diabetes. 2017;66(Suppl 1):A325.Google Scholar
- 45.Lund S, Solimando F, Kohler S, et al. Effect of empagliflozin (EMPA) on diabetic ketoacidosis (DKA) in patients with type 2 diabetes (T2DM): pooled clinical trial data [abstract no. 50]. Diabetologia. 2016;59(Suppl 1):S26–7.Google Scholar
- 50.Boehringer Ingelheim. Boehringer Ingelheim and Lilly announce an academic collaboration with University of Oxford to investigate the effects of empagliflozin in people with chronic kidney disease [media release]. 18 Apr 2018. https://www.boehringer-ingelheim.com.
- 62.American Diabetes Association. Pharmacological approaches to glycemic treatment. Sect. 8. In: Standards of Medical Care in Diabetes-2018. Diabetes Care. 2018;41(Suppl 1):S73–85.Google Scholar
- 63.Garber AJ, Abrahamson MJ, Barzilay JI, et al. Consensus statement by the American Association of Clinical Endocrinologists and American College of Endocrinology on the comprehensive type 2 diabetes management algorithm-2018 executive summary. Endocr Pract. 2018;24(1):91–120.CrossRefPubMedGoogle Scholar
- 64.Canadian Diabetes Association Clinical Practice Guidelines Expert Committee. Pharmacologic management of type 2 diabetes. Can J Diabetes. 2013;37(Suppl 1):S61–8.Google Scholar
- 66.Diabetes Canada. Pharmacologic management of type 2 diabetes: November 2016 interim update. http://guidelines.diabetes.ca. Accessed 8 June 2018.
- 70.NICE. Type 2 diabetes in adults: management. 2017. http://www.nice.org. Accessed 8 June 2018.
- 76.Chilton RJ, Gullestad L, Fitchett D, et al. Effects of empagliflozin on cardiac and vascular hemodynamic markers by subgroups of age, sex, and hypertension in patients with T2DM and high CV Risk: EMPA-REG OUTCOME [abstract no. 452-P and poster]. Diabetes. 2017;66(Suppl 1):A119.Google Scholar
- 78.Neeland IJ, McGuire DK, Fernandez CS, et al. Effect of empagliflozin on anthropometry and indices of visceral and total adiposity in patients with type 2 diabetes and high cardiovascular risk: EMPA-REG OUTCOME [abstract no. 730]. Diabetologia. 2016;59(Suppl 1):S348.Google Scholar
- 80.Cherney DZI, Zinman B, Inzucchi SE, et al. Effects of empagliflozin on the urinary albumin-to-creatinine ratio in patients with type 2 diabetes and established cardiovascular disease: an exploratory analysis from the EMPA-REG OUTCOME randomised, placebo-controlled trial. Lancet Diabetes Endocrinol. 2017;5(8):610–21.CrossRefPubMedGoogle Scholar