Single-pill combination therapy for type 2 diabetes mellitus: linagliptin plus empagliflozin

References

• IDF Diabetes Atlas, 6th edn. International Diabetes Federation, 2013. Available at: http://www.idf.org/sites/default/files/EN_6E_Atlas_Full_0.pdf [Last accessed 2 April 2015]
   Google Scholar
• American Diabetes Association. Standards of medical care in diabetes – 2015. Diabetes Care 2015;38(Suppl 1):S1-93
   PubMed Web of Science ®Google Scholar
• Rydén L, Grant PJ, Anker SD, et al. ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD: The Task Force on diabetes, pre-diabetes, and cardiovascular diseases of the European Society of Cardiology (ESC) and developed in collaboration with the European Association for the Study of Diabetes (EASD). Eur Heart J 2013;34:3035-87
   PubMed Web of Science ®Google Scholar
• Garber AJ, Abrahamson MJ, Barzilay JI, et al. American Association of Clinical Endocrinologists’ comprehensive diabetes management algorithm 2013 consensus statement – executive summary. Endocr Pract 2013;19:536-57
   PubMed Web of Science ®Google Scholar
• 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;38:140-9
   PubMed Web of Science ®Google Scholar
• Phung OJ, Sobieraj DM, Engel SS, Rajpathak SN. Early combination therapy for the treatment of type 2 diabetes mellitus: systematic review and meta-analysis. Diabetes Obes Metab 2014;16:410-17
   PubMed Web of Science ®Google Scholar
• Dailey G, Kim MS, Lian JF. Patient compliance and persistence with antihyperglycemic drug regimens: evaluation of a Medicaid patient population with type 2 diabetes mellitus. Clin Ther 2001;23:1311-20
   PubMed Web of Science ®Google Scholar
• Dailey G, Kim MS, Lian JF. Patient compliance and persistence with anti-hyperglycemic therapy: evaluation of a population of type 2 diabetic patients. J Int Med Res 2002;30:71-9
   PubMed Web of Science ®Google Scholar
• Donnan PT, MacDonald TM, Morris AD. Adherence to prescribed oral hypoglycaemic medication in a population of patients with Type 2 diabetes: a retrospective cohort study. Diabet Med 2002;19:279-84
   PubMed Web of Science ®Google Scholar
• Benford M, Milligan G, Pike J, et al. Fixed-dose combination antidiabetic therapy: real-world factors associated with prescribing choices and relationship with patient satisfaction and compliance. Adv Ther 2012;29:26-40
   PubMed Web of Science ®Google Scholar
• Han S, Iglay K, Davies MJ, et al. Glycemic effectiveness and medication adherence with fixed-dose combination or coadministered dual therapy of antihyperglycemic regimens: a meta-analysis. Curr Med Res Opin 2012;28:969-77
   PubMed Web of Science ®Google Scholar
• Hutchins V, Zhang B, Fleurence RL, et al. A systematic review of adherence, treatment satisfaction and costs, in fixed-dose combination regimens in type 2 diabetes. Curr Med Res Opin 2011;27:1157-68
   PubMed Web of Science ®Google Scholar
• Boehringer Ingelheim and Eli Lilly and Company Announce New Drug Application Filing in the U.S. for the Combination Tablet of Empagliflozin and Linagliptin (Press release, 14 April 2014). Eli Lilly, 2014. Available at: http://lilly.mediaroom.com/index.php?s=9042&item=137292 [Last accessed 2 April 2015]
   Google Scholar
• Holst JJ. The physiology of glucagon-like peptide 1. Physiol Rev 2007;87:1409-39
   PubMed Web of Science ®Google Scholar
• Scheen AJ. DPP-4 inhibitors in the management of type 2 diabetes: A critical review of head-to-head trials. Diabetes Metab 2012;38:89-101
   PubMed Web of Science ®Google Scholar
• Tradjenta (linagliptin) label. US Food and Drug Administration, May 2014. Available at: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/201280s009lbl.pdf [Last accessed 16 September 2014]
   Google Scholar
• Grunberger G. Clinical utility of the dipeptidyl peptidase-4 inhibitor linagliptin. Postgrad Med 2013;125:79-90
   PubMed Web of Science ®Google Scholar
• McGill JB. Linagliptin for type 2 diabetes mellitus: a review of the pivotal clinical trials. Ther Adv Endocrinol Metab 2012;3:113-24
   PubMedGoogle Scholar
• Del Prato S, Barnett AH, Huisman H, et al. Effect of linagliptin monotherapy on glycaemic control and markers of beta-cell function in patients with inadequately controlled type 2 diabetes: a randomized controlled trial. Diabetes Obes Metab 2011;13:258-67
   PubMed Web of Science ®Google Scholar
• Barnett AH, Patel S, Harper R, et al. Linagliptin monotherapy in type 2 diabetes patients for whom metformin is inappropriate: an 18-week randomized, double-blind, placebo-controlled phase III trial with a 34-week active-controlled extension. Diabetes Obes Metab 2012;14:1145-54
   PubMed Web of Science ®Google Scholar
• Haak T, Meinicke T, Jones R, et al. Initial combination of linagliptin and metformin improves glycaemic control in type 2 diabetes: a randomized, double-blind, placebo-controlled study. Diabetes Obes Metab 2012;14:565-74
   PubMed Web of Science ®Google Scholar
• Haak T, Meinicke T, Jones R, et al. Initial combination of linagliptin and metformin in patients with type 2 diabetes: efficacy and safety in a randomised, double-blind 1-year extension study. Int J Clin Pract 2013;67:1283-93
   PubMed Web of Science ®Google Scholar
• Gomis R, Espadero RM, Jones R, et al. Efficacy and safety of initial combination therapy with linagliptin and pioglitazone in patients with inadequately controlled type 2 diabetes: a randomized, double-blind, placebo-controlled study. Diabetes Obes Metab 2011;13:653-61
   PubMed Web of Science ®Google Scholar
• Taskinen MR, Rosenstock J, Tamminen I, et al. Safety and efficacy of linagliptin as add-on therapy to metformin in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled study. Diabetes Obes Metab 2011;13:65-74
   PubMed Web of Science ®Google Scholar
• Lewin AJ, Arvay L, Liu D, et al. Efficacy and tolerability of linagliptin added to a sulfonylurea regimen in patients with inadequately controlled type 2 diabetes mellitus: an 18-week, multicenter, randomized, double-blind, placebo-controlled trial. Clin Ther 2012;34:1909-19 e15
   PubMed Web of Science ®Google Scholar
• Yki-Järvinen H, Rosenstock J, Durán-Garcia S, et al. Effects of adding linagliptin to basal insulin regimen for inadequately controlled type 2 diabetes: a >/=52-week randomized, double-blind study. Diabetes Care 2013;36:3875-81
   PubMed Web of Science ®Google Scholar
• McGill JB, Sloan L, Newman J, et al. Long-term efficacy and safety of linagliptin in patients with type 2 diabetes and severe renal impairment: a 1-year, randomized, double-blind, placebo-controlled study. Diabetes Care 2013;36:237-44
   PubMed Web of Science ®Google Scholar
• Groop PH, Del Prato S, Taskinen MR, et al. Linagliptin treatment in subjects with type 2 diabetes with and without mild-to-moderate renal impairment. Diabetes Obes Metab 2014;16:560-8
   PubMed Web of Science ®Google Scholar
• McGill JB, Barnett AH, Lewin AJ, et al. Linagliptin added to sulphonylurea in uncontrolled type 2 diabetes patients with moderate-to-severe renal impairment. Diab Vasc Dis Res 2014;11:34-40
   PubMed Web of Science ®Google Scholar
• Barnett AH, Huisman H, Jones R, et al. Linagliptin for patients aged 70 years or older with type 2 diabetes inadequately controlled with common antidiabetes treatments: a randomised, double-blind, placebo-controlled trial. Lancet 2013;382:1413-23
   PubMed Web of Science ®Google Scholar
• Thrasher J, Daniels K, Patel S, et al. Efficacy and safety of linagliptin in Black/African American patients with type 2 diabetes: a 6 month, randomized, double-blind, placebo-controlled study. Endocr Pract 2014;20:412-20
   PubMed Web of Science ®Google Scholar
• Davidson JA, Lajara R, Aguilar RB, et al. Efficacy and safety of linagliptin in Hispanic/Latino patients with type 2 diabetes mellitus: a pooled analysis from six randomized placebo-controlled phase 3 trials. BMJ Open Diab Res Care 2014;2:e000020
   PubMedGoogle Scholar
• Kawamori R, Inagaki N, Araki E, et al. Linagliptin monotherapy provides superior glycaemic control versus placebo or voglibose with comparable safety in Japanese patients with type 2 diabetes: a randomized, placebo and active comparator-controlled, double-blind study. Diabetes Obes Metab 2012;14:348-57
   PubMed Web of Science ®Google Scholar
• Zeng Z, Yang JK, Tong N, et al. Efficacy and safety of linagliptin added to metformin and sulphonylurea in Chinese patients with type 2 diabetes: a sub-analysis of data from a randomised clinical trial. Curr Med Res Opin 2013;29:1-9
   Google Scholar
• Lajara R, Aguilar R, Hehnke U, et al. Efficacy and safety of linagliptin in subjects with long-standing type 2 diabetes mellitus (>10 years): evidence from pooled data of randomized, double-blind, placebo-controlled, phase III trials. Clin Ther 2014;36:1595-605
   PubMed Web of Science ®Google Scholar
• Johansen OE, Neubacher D, von Eynatten M, et al. Cardiovascular safety with linagliptin in patients with type 2 diabetes mellitus: a pre-specified, prospective, and adjudicated meta-analysis of a phase 3 programme. Cardiovasc Diabetol 2012;11:3
   PubMed Web of Science ®Google Scholar
• Results of new meta-analysis regarding CV events in linagliptin Phase 3 trials presented at ADA (Press release, 25 June 2013). Boehringer Ingelheim GmbH, 2013. Available at: http://www.boehringer-ingelheim.com/news/news_releases/press_releases/2013/25_june_2013_linagliptin.html [Last accessed 2 April 2015]
   Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• Lajara R. The potential role of sodium glucose co-transporter 2 inhibitors in combination therapy for type 2 diabetes mellitus. Expert Opin Pharmacother 2014;15:2565-85
   PubMed Web of Science ®Google Scholar
• Chen LH, Leung PS. Inhibition of the sodium glucose co-transporter-2: its beneficial action and potential combination therapy for type 2 diabetes mellitus. Diabetes Obes Metab 2013;15:392-402
   PubMed Web of Science ®Google Scholar
• Jardiance (empagliflozin) label. US Food and Drug Administration, August 2014. Available at: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/204629s000lbl.pdf [Last accessed 18 September 2014]
   Google Scholar
• Pooled analysis data showed improvements in glycaemic parameters, body weight and blood pressure with investigational agent empagliflozin in adults with type 2 diabetes. (Press release, 24 September 2013.) Boehringer Ingelheim GmbH, 2013. Available at: http://www.boehringer-ingelheim.com/news/news_releases/press_releases/2013/24_september_2013empagliflozin.html [Last accessed 11 March 2014]
   Google Scholar
• 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;2:369-84
   PubMed Web of Science ®Google Scholar
• Häring 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;36:3396-404
   PubMed Web of Science ®Google Scholar
• Häring H-U, 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;37:1650-9
   PubMed Web of Science ®Google Scholar
• 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;16:147-58
   PubMed Web of Science ®Google Scholar
• 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;1:208-19
   PubMed Web of Science ®Google Scholar
• Tikkanen I, Narko K, Zeller C, et al. Empagliflozin reduces blood pressure in patients with type 2 diabetes and hypertension. Diabetes Care 2015;38:420-8
   PubMed Web of Science ®Google Scholar
• Ridderstråle 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
   PubMed Web of Science ®Google Scholar
• 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;37:1815-23
   PubMed Web of Science ®Google Scholar
• Roden M, Weng J, Merker L, et al. Empagliflozin (EMPA) monotherapy for ≥76 weeks in drug-naïve patients with type 2 diabetes (T2DM). Diabetes 2014;63(Suppl 1):A69
   Google Scholar
• Kovacs C, Seshiah V, Merker L, et al. Empagliflozin (EMPA) for ≥76 weeks as add-on to pioglitazone with or without metformin in patients with type 2 diabetes (T2DM). Diabetes 2014;63(Suppl 1):A273
   Google Scholar
• Merker L, Häring H-U, Vedel Christiansen A, et al. Empagliflozin (EMPA) for ≥76 weeks as add-on to metformin in patients with type 2 diabetes (T2DM). Diabetes 2014;63(Suppl 1):A278
   Google Scholar
• Häring H-U, Merker L, Vedel Christiansen A, et al. Empagliflozin (EMPA) for ≥76 weeks as add-on to metformin plus sulfonylurea (SU) in patients with type 2 diabetes (T2DM). Diabetes 2014;63(Suppl 1):A280
   Google Scholar
• Zinman B, Inzucchi SE, Lachin JM, et al. Rationale, design, and baseline characteristics of a randomized, placebo-controlled cardiovascular outcome trial of empagliflozin (EMPA-REG OUTCOME™). Cardiovasc Diabetol 2014;13:102
   PubMed Web of Science ®Google Scholar
• Ferrannini E, Muscelli E, Frascerra S, et al. Metabolic response to sodium-glucose cotransporter 2 inhibition in type 2 diabetic patients. J Clin Invest 2013;124:499-508
   Web of Science ®Google Scholar
• Merovci A, Solis-Herrera C, Daniele G, et al. Dapagliflozin improves muscle insulin sensitivity but enhances endogenous glucose production. J Clin Invest 2014;124:509-14
   PubMed Web of Science ®Google Scholar
• Muscelli E, Casolaro A, Gastaldelli A, et al. Mechanisms for the antihyperglycemic effect of sitagliptin in patients with type 2 diabetes. J Clin Endocrinol Metab 2012;97:2818-26
   PubMed Web of Science ®Google Scholar
• Forst T, Anastassiadis E, Diessel S, et al. Effect of linagliptin compared to glimepiride on postprandial glucose metabolism, islet cell function, and vascular function parameters in patients with type 2 diabetes mellitus on ongoing metformin treatment. Diabetes Metab Res Rev 2014;30:582-9
   PubMed Web of Science ®Google Scholar
• Invokamet (canagliflozin and metformin hydrochloride) label. US Food and Drug Administration, March 2015. Available at: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/204353s002lbl.pdf [Last accessed 2 April 2015]
   Google Scholar
• Xigduo XR (dapagliflozin and metformin hydrochloride extended-release) label. US Food and Drug Administration, October 2014. Available at: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/205649s000lbl.pdf [Last accessed 23 February 2015]
   Google Scholar
• Glyxambi (empagliflozin and linagliptin) label. US Food and Drug Administration, January 2015. Available at: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/206073s000lbl.pdf [Last accessed 23 February 2015]
   Google Scholar
• Jabbour SA, Hardy E, Sugg J, Parikh S. Dapagliflozin is effective as add-on therapy to sitagliptin with or without metformin: a 24-week, multicenter, randomized, double-blind, placebo-controlled study. Diabetes Care 2014;37:740-50
   PubMed Web of Science ®Google Scholar
• Rosenstock J, Hansen L, Zee P, et al. Dual add-on therapy in type 2 diabetes poorly controlled with metformin monotherapy: a randomized double-blind trial of saxagliptin plus dapagliflozin addition versus single addition of saxagliptin or dapagliflozin to metformin. Diabetes Care 2015;38:376-83
   PubMed Web of Science ®Google Scholar
• Friedrich C, Metzmann K, Rose P, et al. A randomized, open-label, crossover study to evaluate the pharmacokinetics of empagliflozin and linagliptin after coadministration in healthy male volunteers. Clin Ther 2013;35:A33-42
   PubMed Web of Science ®Google Scholar
• Brand T, Macha S, Mattheus M, et al. Pharmacokinetics of empagliflozin, a sodium glucose cotransporter-2 (SGLT-2) inhibitor, coadministered with sitagliptin in healthy volunteers. Adv Ther 2012;29:889-99
   PubMed Web of Science ®Google Scholar
• Lewin A, DeFronzo RA, Patel S, et al. Initial combination of empagliflozin and linagliptin in subjects with type 2 diabetes. Diabetes Care 2015;38:394-402
   PubMed Web of Science ®Google Scholar
• DeFronzo RA, Lewin A, Patel S, et al. Combination of empagliflozin and linagliptin as second-line therapy in subjects with type 2 diabetes inadequately controlled on metformin. Diabetes Care 2015;38:384-93
   PubMed Web of Science ®Google Scholar
• Klein T, Kern M, Klöting N, et al. Combination of empagliflozin and linagliptin shows promise in a rodent model of non-alcoholic fatty liver disease. Diabetologia 2014;57(Suppl 1):S518-19
   Google Scholar
• Williams-Herman D, Johnson J, Teng R, et al. Efficacy and safety of initial combination therapy with sitagliptin and metformin in patients with type 2 diabetes: a 54-week study. Curr Med Res Opin 2009;25:569-83
   PubMed Web of Science ®Google Scholar
• 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;8:262-75 e9
   PubMed Web of Science ®Google Scholar
• Schernthaner G, Barnett AH, Emser A, et al. Safety and tolerability of linagliptin: a pooled analysis of data from randomized controlled trials in 3572 patients with type 2 diabetes mellitus. Diabetes Obes Metab 2012;14:470-8
   PubMed Web of Science ®Google Scholar
• Geerlings S, Fonseca V, Castro-Diaz D, et al. Genital and urinary tract infections in diabetes: Impact of pharmacologically-induced glucosuria. Diabetes Res Clin Pract 2014;103:373-81
   PubMed Web of Science ®Google Scholar
• Kim G, Gerich JE, Salsali A, et al. Empagliflozin (EMPA) increases genital infections but not urinary tract infections (UTIs) in pooled data from four pivotal phase III trials. Diabetes 2013;62(Suppl 1):LB21 (Abstract 74-LB)
   Google Scholar