571
Views
13
CrossRef citations to date
0
Altmetric
Drug Safety Evaluations

A Safety Evaluation of Empagliflozin for the Treatment of Type 2 Diabetes

, &
Pages 393-402 | Received 19 Nov 2015, Accepted 21 Dec 2015, Published online: 02 Feb 2016

References

  • Inzucchi SE, Zinman B, Wanner C, et al. SGLT-2 inhibitors and cardiovascular risk: proposed pathways and review of ongoing outcome trials. Diab Vasc Dis Res. 2015;12:90–100.
  • Ehrenkranz JR, Lewis NG, Kahn CR, et al. Phlorizin: a review. Diabetes Metab Res Rev. 2005;21:31–38.
  • White JR Jr. Empagliflozin, an SGLT2 inhibitor for the treatment of type 2 diabetes mellitus: a review of the evidence. Ann Pharmacother. 2015;49:582–598.
  • Roden M, Weng J, Eilbracht J, et al. Empagliflozin monotherapy with sitagliptin as an active comparator in patients with type 2 diabetes: a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Diabetes Endocrinol. 2013;1:208–219.
  • Haring HU, Merker L, Seewaldt-Becker E, et al. Empagliflozin as add-on to metformin in patients with type 2 diabetes: a 24-week, randomized, double-blind, placebo-controlled trial. Diabetes Care. 2014;37:1650–1659.
  • Haring HU, Merker L, Seewaldt-Becker E, et al. Empagliflozin as add-on to metformin plus sulfonylurea in patients with type 2 diabetes: a 24-week, randomized, double-blind, placebo-controlled trial. Diabetes Care. 2013;36:3396–3404.
  • 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;16:147–158.
  • Rosenstock J, Jelaska A, Frappin G, et al. Improved glucose control with weight loss, lower insulin doses, and no increased hypoglycemia with empagliflozin added to titrated multiple daily injections of insulin in obese inadequately controlled type 2 diabetes. Diabetes Care. 2014;37:1815–1823.
  • Ridderstrale M, Andersen KR, Zeller C, et al. Comparison of empagliflozin and glimepiride as add-on to metformin in patients with type 2 diabetes: a 104-week randomised, active-controlled, double-blind, phase 3 trial. Lancet Diabetes Endocrinol. 2014;2:691–700.
  • Vallon V, Platt KA, Cunard R, et al. SGLT2 mediates glucose reabsorption in the early proximal tubule. J Am Soc Nephrol. 2011;22:104–112.
  • Wright EM, Loo DD, Hirayama BA. Biology of human sodium glucose transporters. Physiol Rev. 2011;91:733–794.
  • Duckworth W, Abraira C, Moritz T, et al. Glucose control and vascular complications in veterans with type 2 diabetes. N Engl J Med. 2009;360:129–139.
  • Hediger MA, Rhoads DB. Molecular physiology of sodium-glucose cotransporters. Physiol Rev. 1994;74:993–1026.
  • DeFronzo RA, Davidson JA, Del Prato S. The role of the kidneys in glucose homeostasis: a new path towards normalizing glycaemia. Diabetes Obes Metab. 2012;14:5–14.
  • Rahmoune H, Thompson PW, Ward JM, et al. Glucose transporters in human renal proximal tubular cells isolated from the urine of patients with non-insulin-dependent diabetes. Diabetes. 2005;54:3427–3434.
  • Seman LMS, Nehmiz G, et al. Empagliflozin (BI 10773), a potent and selective SGLT2 inhibitor, induces dose-dependent glucosuria in healthy subjects. Clin Pharmacol Drug Dev. 2013;2:152–161.
  • Heise T, Seman L, Macha S, et al. Safety, tolerability, pharmacokinetics, and pharmacodynamics of multiple rising doses of empagliflozin in patients with type 2 diabetes mellitus. Diabetes Ther. 2013;4:331–345.
  • Heise T, Seewaldt-Becker E, Macha S, et al. Safety, tolerability, pharmacokinetics and pharmacodynamics following 4 weeks’ treatment with empagliflozin once daily in patients with type 2 diabetes. Diabetes Obes Metab. 2013;15:613–621.
  • Kanada S, Koiwai K, Taniguchi A, et al. Pharmacokinetics, pharmacodynamics, safety and tolerability of 4 weeks’ treatment with empagliflozin in Japanese patients with type 2 diabetes mellitus. J Diabetes Investig. 2013;4:613–617.
  • Empagliflozin Prescribing Information. [cited 2015 Aug 24]. Available from: http://bidocs.boehringer-ingelheim.com/BIWebAccess/ViewServlet.ser?docBase=renetnt&folderPath=/Prescribing+Information/PIs/Jardiance/jardiance.pdf.
  • Seman LMSNG, et al. Empagliflozin (BI 10773), a potent and selective SGLT2 inhibitor, induces dose-dependent glucosuria in healthy subjects. Clin Pharmacol Drug Dev. 2013;2:152–161.
  • Sarashina A, Koiwai K, Seman LJ, et al. Safety, tolerability, pharmacokinetics and pharmacodynamics of single doses of empagliflozin, a sodium glucose cotransporter 2 (SGLT2) inhibitor, in healthy Japanese subjects. Drug Metab Pharmacokinet. 2013;28:213–219.
  • Rosenstock J, Jelaska A, Frappin G, et al. Improved glucose control with weight loss, lower insulin doses, and no increased hypoglycemia with empagliflozin added to titrated multiple daily injections of insulin in obese inadequately controlled type 2 diabetes. Diabetes Care. 2014;37:1815–1823.
  • Liakos A, Karagiannis T, Athanasiadou E, et al. Efficacy and safety of empagliflozin for type 2 diabetes: a systematic review and meta-analysis. Diabetes Obes Metab. 2014;16:984–993.
  • Chilton R, Tikkanen I, Cannon CP, et al. Effects of empagliflozin on blood pressure and markers of arterial stiffness and vascular resistance in patients with type 2 diabetes. Diabetes Obes Metab. 2015;17:1180–1193.
  • Neeland IJ, McGuire DK, Chilton B, et al. Empagliflozin reduces body weight and indices of adipose distribution in patients with type 2 diabtes mellitus. Diab Vasc Dis Res. 2015. doi:10.1177/1479164115616901. [Epub ahead of print].
  • Monami M, Nardini C, Mannucci E. Efficacy and safety of sodium glucose co-transport-2 inhibitors in type 2 diabetes: a meta-analysis of randomized clinical trials. Diabetes Obes Metab. 2014;16:457–466.
  • Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015. [ Epub ahead of print]. doi:10.1056/NEJMoa1504720.
  • Abdul-Ghani MA, Norton L, Defronzo RA. Role of sodium-glucose cotransporter 2 (SGLT 2) inhibitors in the treatment of type 2 diabetes. Endocr Rev. 2011;32:515–531.
  • Tikkanen I, Narko K, Zeller C, et al. Empagliflozin reduces blood pressure in patients with type 2 diabetes and hypertension. Diabetes Care. 2015;38:420–428.
  • Baker WL, Smyth LR, Riche DM, et al. Effects of sodium-glucose co-transporter 2 inhibitors on blood pressure: a systematic review and meta-analysis. J Am Soc Hypertens. 2014;8:26275.e9.
  • FDA Drug Safety Communication: FDA warns that SGLT2 inhibitors for diabetes may result in a serious condition of too much acid in the blood. [cited 2015 Aug 24]. Available from: http://www.fda.gov/Drugs/DrugSafety/ucm446845.htm.
  • Perkins BA, Cherney DZ, Partridge H, et al. Sodium-glucose cotransporter 2 inhibition and glycemic control in type 1 diabetes: results of an 8-week open-label proof-of-concept trial. Diabetes Care. 2014;37:1480–1483.
  • Taylor SI, Blau JE, Rother KI. SGLT2 inhibitors may predispose to ketoacidosis. J Clin Endocrinol Metab. 2015;100:2849–2852.
  • Invokana and Invokamet (canagliflozin): Drug Safety Communication - New Information on Bone Fracture Risk and Decreased Bone Mineral Density. [cited 2015 Dec 10]. Available from: http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm461876.htm.
  • Kwon H CANA: clinical efficacy and safety. Endocrinology and Metabolic Drugs Advisory Committee Meeting. 2013. [cited 2015 Dec 10]. Available from http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/EndocrinologicandMetabolicDrugsAdvisoryCommittee/UCM336234.pdf.
  • Taylor SI, Blau JE, Rother KI. Possible adverse effects of SGLT2 inhibitors on bone. Lancet Diabetes Endocrinol. 2015;3:8–10.
  • Gallo LA, Wright EM, Vallon V. Probing SGLT2 as a therapeutic target for diabetes: basic physiology and consequences. Diab Vasc Dis Res. 2015;12:78–89.
  • 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;2:369–384.
  • Nissen SE, Wolski K. Rosiglitazone revisited: an updated meta-analysis of risk for myocardial infarction and cardiovascular mortality. Arch Intern Med. 2010;170:1191–1201.
  • Graham DJ, Ouellet-Hellstrom R, MaCurdy TE, et al. Risk of acute myocardial infarction, stroke, heart failure, and death in elderly Medicare patients treated with rosiglitazone or pioglitazone. JAMA. 2010;304:411–418.
  • Varas-Lorenzo C, Margulis AV, Pladevall M, et al. The risk of heart failure associated with the use of noninsulin blood glucose-lowering drugs: systematic review and meta-analysis of published observational studies. BMC Cardiovasc Disord. 2014;14:129.
  • Scirica BM, Braunwald E, Raz I, et al. Heart failure, saxagliptin, and diabetes mellitus: observations from the SAVOR-TIMI 53 randomized trial. Circulation. 2014;130:1579–1588.
  • Cherney DZ, Perkins BA, Soleymanlou N, et al. Renal hemodynamic effect of sodium-glucose cotransporter 2 inhibition in patients with type 1 diabetes mellitus. Circulation. 2014;129:587–597.
  • Lapuerta P, Zambrowicz B, Strumph P, et al. Development of sotagliflozin, a dual sodium-dependent glucose transporter 1/2 inhibitor. Diab Vasc Dis Res. 2015;12:101–110.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.