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

The Lancet Diabetes and Endocrinology

Volumn 2, Issue 5, 2014, Pages 369-384

  Barnett, Anthony H ^a   Mithal, Ambrish ^b   Manassie, Jenny ^c   Jones, Russell ^c   Rattunde, Henning ^d   Woerle, Hans J ^d   Broedl, Uli C ^d  

^a UNIVERSITY HOSPITALS BIRMINGHAM NHS FOUNDATION TRUST   (United Kingdom)

^b MEDANTA THE MEDICITY   (India)

^c BOEHRINGER INGELHEIM LTD   (United Kingdom)

^d BOEHRINGER INGELHEIM PHARMA GMBH AND CO KG   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

ALBUMIN; CREATININE; EMPAGLIFLOZIN; HEMOGLOBIN A1C; PLACEBO; ANTIDIABETIC AGENT; BENZHYDRYL DERIVATIVE; GLUCOSIDE; INSULIN; METFORMIN; SULFONYLUREA;

ADULT; ALBUMIN TO CREATININE RATIO; ARTHRALGIA; ARTICLE; BACKACHE; CHRONIC KIDNEY DISEASE; CLINICAL EFFECTIVENESS; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; COUGHING; DIARRHEA; DISEASE SEVERITY; DIZZINESS; DOUBLE BLIND PROCEDURE; DRUG EFFICACY; DRUG RESPONSE; DRUG SAFETY; DRUG TOLERABILITY; FEMALE; FEVER; FOLLOW UP; GLOMERULUS FILTRATION RATE; HEART ATRIUM FIBRILLATION; HUMAN; HYPERKALEMIA; HYPERTENSION; HYPOGLYCEMIA; MAJOR CLINICAL STUDY; MALE; MIDDLE AGED; MULTICENTER STUDY; NAUSEA; NON INSULIN DEPENDENT DIABETES MELLITUS; OUTCOME ASSESSMENT; PAIN; PARAMETERS; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; RHINOPHARYNGITIS; SYNDROME DELINEATION; UPPER RESPIRATORY TRACT INFECTION; URINARY TRACT INFECTION; VOMITING; CLINICAL TRIAL; COMPLICATION; DIABETES MELLITUS, TYPE 2; DRUG COMBINATION; PHASE 3 CLINICAL TRIAL; RENAL INSUFFICIENCY, CHRONIC; TREATMENT OUTCOME; ACUTE PYELONEPHRITIS; ADD ON THERAPY; ANEMIA; DOSE RESPONSE; DRUG DOSE COMPARISON; DRUG WITHDRAWAL; FRACTURE; GENITAL TRACT INFECTION; HEADACHE; HYPERGLYCEMIA; LIMB PAIN; MORNING DOSAGE; UROSEPSIS;

BENZHYDRYL COMPOUNDS; DIABETES MELLITUS, TYPE 2; DOUBLE-BLIND METHOD; DRUG THERAPY, COMBINATION; FEMALE; GLUCOSIDES; HUMANS; HYPOGLYCEMIC AGENTS; MALE; MIDDLE AGED; RENAL INSUFFICIENCY, CHRONIC; TREATMENT OUTCOME;

EID: 84899961819     PISSN: 22138587     EISSN: None     Source Type: Journal    
DOI: 10.1016/S2213-8587(13)70208-0     Document Type: Article

References (31)

1. KDIGO 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney Int Suppl 2013, 3:1-150. Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group.
2. Meyers JL, Candrilli SD, Kovacs B Type 2 diabetes mellitus and renal impairment in a large outpatient electronic medical records database: rates of diagnosis and antihyperglycemic medication dose adjustment. Postgrad Med 2011, 123:133-143.
3. Coll-de-Tuero G, Mata-Cases M, Rodriguez-Poncelas A, et al. Chronic kidney disease in the type 2 diabetic patients: prevalence and associated variables in a random sample of 2642 patients of a Mediterranean area. BMC Nephrol 2012, 13:87.
4. Koro CE, Lee BH, Bowlin SJ Antidiabetic medication use and prevalence of chronic kidney disease among patients with type 2 diabetes mellitus in the United States. Clin Ther 2009, 31:2608-2617.
5. Go AS, Chertow GM, Fan D, McCulloch CE, Hsu CY Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Engl J Med 2004, 351:1296-1305.
6. Schramm TK, Gislason GH, Kober L, et al. Diabetes patients requiring glucose-lowering therapy and nondiabetics with a prior myocardial infarction carry the same cardiovascular risk: a population study of 3·3 million people. Circulation 2008, 117:1945-1954.
7. Fox CS, Matsushita K, Woodward M, et al. Associations of kidney disease measures with mortality and end-stage renal disease in individuals with and without diabetes: a meta-analysis. Lancet 2012, 380:1662-1673.
8. Standards of medical care in diabetes 2012. Diabetes Care 2012, 35:S11-S63. American Diabetes Association.
9. KDOQI clinical practice guideline for diabetes and CKD: 2012 update. Am J Kidney Dis 2012, 60:850-886. National Kidney Foundation.
10. 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.
11. Grempler R, Thomas L, Eckhardt M, et al. Empagliflozin, a novel selective sodium glucose cotransporter-2 (SGLT-2) inhibitor: characterisation and comparison with other SGLT-2 inhibitors. Diabetes Obes Metab 2012, 14:83-90.
12. 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.
13. 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.
14. Häring H-U, Merker L, Seewaldt-Becker E, et al. Empagliflozin as add-on to metformin for 24 weeks improves glycemic control in patients with type 2 diabetes (T2DM). Diabetes 2013, 62(suppl 1):A282.
15. Häring H-U, 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.
16. 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 2013, published online Aug 22. http://dx.doi.org/10.1111/dom.12188.
17. Macha S, Mattheus M, Halabi A, Pinnetti S, Woerle HJ, Broedl UC Pharmacokinetics, pharmacodynamics and safety of empagliflozin, a sodium glucose cotransporter 2 (SGLT2) inhibitor, in subjects with renal impairment. Diabetes Obes Metab 2013, published online Aug 19. http://dx.doi.org/10.1111/dom.12182.
18. Ferrannini E, Seman L, Seewaldt-Becker E, Hantel S, Pinnetti S, Woerle H A phase IIb, randomised, placebo-controlled study of the SGLT2 inhibitor empagliflozin in patients with type 2 diabetes. Diabetes Obes Metab 2013, 15:721-728.
19. Rosenstock J, Seman LJ, Jelaska A, et al. Efficacy and safety of empagliflozin, a sodium glucose cotransporter 2 (SGLT2) inhibitor, as add-on to metformin in type 2 diabetes with mild hyperglycaemia. Diabetes Obes Metab 2013, 15:1154-1160.
20. Seman L, Macha S, Nehmiz G, et al. Empagliflozin (BI 10773), a potent and selective SGLT-2 inhibitor, induces dose-dependent glucosuria in healthy subjects. Clinical Pharm in Drug Dev 2013, 2:152-161.
21. Rosenstock J, Jelaska A, Wang F, Kim G, Broedl U, Woerle H-J Empagliflozin as add-on to basal insulin for 78 weeks improves glycemic control with weight loss in insulin-treated type 2 diabetes (T2DM). Diabetes 2013, 62(suppl 1):A285.
22. Scheen AJ Pharmacokinetic considerations for the treatment of diabetes in patients with chronic kidney disease. Expert Opin Drug Metab Toxicol 2013, 9:529-550.
23. KDOQI clinical practice guidelines and clinical practice recommendations for diabetes and chronic kidney disease. Am J Kidney Dis 2007, 49:S12-154. KDOQI.
24. Kohan DE, Fioretto P, Tang W, List JF Long-term study of patients with type 2 diabetes and moderate renal impairment shows that dapagliflozin reduces weight and blood pressure but does not improve glycemic control. Kidney Int 2013, published online Sept 25. http://dx.doi.org/10.1038/ki.2013.356.
25. Yale JF, Bakris G, Cariou B, et al. Efficacy and safety of canagliflozin in subjects with type 2 diabetes and chronic kidney disease. Diabetes Obes Metab 2013, 15:463-473.
26. FDA briefing document NDA 202293: dapagliflozin tablets, 5 and 10 mg-Advisory Committee Meeting (July 19, 2011) FDA, (accessed July 29, 2013). http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/Endocrinologicand%20MetabolicDrugsAdvisoryCommittee/UCM262994.pdf.
27. FDA briefing document NDA 204042: invokana (canagliflozin) tablets-Endocrinologic and Metabolic Drugs Advisory Committee Meeting (Jan 10, 2013) FDA, (accessed July 29, 2013). http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/EndocrinologicandMetabolicDrugsAdvisoryCommittee/UCM334550.pdf.
28. Cherney DZ, Perkins BA, Soleymanlou N, et al. The renal hemodynamic effect of SGLT2 inhibition in patients with type 1 diabetes. Circulation 2013, published online Dec 13. http://dx.doi.org/10.1161/CIRCULATIONAHA.113.005081.
29. Schnaper HW Remnant nephron physiology and the progression of chronic kidney disease. Pediatr Nephrol 2013, published online May 29. http://dx.doi.org/10.1007/s00467-013-2494-8.
30. Gaspari F, Ruggenenti P, Porrini E, et al. The GFR and GFR decline cannot be accurately estimated in type 2 diabetics. Kidney Int 2013, 84:164-173.
31. Rossing P, Rossing K, Gaede P, Pedersen O, Parving HH Monitoring kidney function in type 2 diabetic patients with incipient and overt diabetic nephropathy. Diabetes Care 2006, 29:1024-1030.