Efficacy and safety of Lixi Lan, a Titratable Fixed-Ratio Combination of Lixisenatide and Insulin Glargine, Versus Insulin Glargine in type 2 diabetes inadequately controlled on Metformin Monotherapy: The LixiLan proof-of-concept randomized trial

Diabetes Care

Volumn 39, Issue 9, 2016, Pages 1579-1586

  Rosenstock, Julio ^a   Diamant, Michaela ^b   Aroda, Vanita R ^c   Silvestre, Louise ^d   Souhami, Elisabeth ^d   Zhou, Tianyue ^d   Perfetti, Riccardo ^d   Fonseca, Vivian ^e  

^a DALLAS DIABETES AND ENDOCRINE CENTER AT MEDICAL CITY   (United States)

^b VU UNIVERSITY MEDICAL CENTER   (Netherlands)

^c MEDSTAR RESEARCH INSTITUTE   (United States)

^d SANOFI   (France)

^e TULANE UNIVERSITY HEALTH SCIENCES CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

GLUCOSE; HEMOGLOBIN A1C; INSULIN GLARGINE; INSULIN GLARGINE PLUS LIXISENATIDE; LIXISENATIDE; METFORMIN; UNCLASSIFIED DRUG; ANTIDIABETIC AGENT; DRUG COMBINATION; GLUCOSE BLOOD LEVEL; GLYCOSYLATED HEMOGLOBIN; PEPTIDE;

ADULT; AGE; ARTICLE; BODY MASS; CONFUSION; CONSTIPATION; CONTROLLED STUDY; DIARRHEA; DISEASE DURATION; DIZZINESS; DRUG DOSE TITRATION; DRUG EFFICACY; DRUG SAFETY; DYSPEPSIA; FEMALE; GLUCOSE BLOOD LEVEL; HEADACHE; HEMOGLOBIN BLOOD LEVEL; HUMAN; HYPERSENSITIVITY; HYPOGLYCEMIA; INCIDENCE; MALE; NON INSULIN DEPENDENT DIABETES MELLITUS; OPEN STUDY; OVARY CANCER; PARALLEL DESIGN; PHASE 2 CLINICAL TRIAL; RANDOMIZED CONTROLLED TRIAL; STOMACH DISTENSION; TREATMENT DURATION; VOMITING; WEIGHT CHANGE; AGED; BODY WEIGHT; CHEMICALLY INDUCED; CLINICAL TRIAL; COMBINATION DRUG THERAPY; COMPARATIVE STUDY; DIABETES MELLITUS, TYPE 2; DRUG COMBINATION; METABOLISM; MIDDLE AGED; POSTPRANDIAL STATE; RISK; SAFETY;

AGED; BLOOD GLUCOSE; BODY WEIGHT; DIABETES MELLITUS, TYPE 2; DRUG COMBINATIONS; DRUG THERAPY, COMBINATION; FEMALE; HEMOGLOBIN A, GLYCOSYLATED; HUMANS; HYPOGLYCEMIA; HYPOGLYCEMIC AGENTS; INSULIN GLARGINE; MALE; METFORMIN; MIDDLE AGED; PEPTIDES; POSTPRANDIAL PERIOD; RISK; SAFETY;

EID: 84982820694     PISSN: 01495992     EISSN: 19355548     Source Type: Journal    
DOI: 10.2337/dc16-0046     Document Type: Article

References (31)

1. Inzucchi SE, Bergenstal RM, Buse JB, et al. Management of hyperglycaemia in type 2 diabetes, 2015: A patient-centred approach. Update to a position statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetologia 2015;58:429-442
2. Aschner P, Chan J, Owens DR, et al.; EASIE investigators. Insulin glargine versus sitagliptin in insulin-naive patients with type 2 diabetes mellitus uncontrolled on metformin (EASIE): A multicentre, randomised open-label trial. Lancet 2012;379:2262-2269
3. Bolli GB, Riddle MC, Bergenstal RM, et al.; on behalf of the EDITION 3 study investigators. New insulin glargine 300 U/ml compared with glargine 100 U/ml in insulin-naïve people with type 2 diabetes on oral glucose-lowering drugs: A randomized controlled trial (EDITION 3). Diabetes Obes Metab 2015;17:386-394
4. RiddleMC, Rosenstock J, Gerich J; Insulin Glargine 4002 Study Investigators. The treat-to-target trial: Randomized addition of glargine or human NPH insulin to oral therapy of type 2 diabetic patients. Diabetes Care 2003;26:3080-3086
5. Fonseca V, Gill J, Zhou R, Leahy J. An analysis of early insulin glargine added to metformin with or without sulfonylurea: Impact on glycaemic control and hypoglycaemia. Diabetes Obes Metab 2011;13:814-822
6. Meier JJ, Rosenstock J, Hincelin-Méry A, et al. Contrasting effects of lixisenatide and liraglutide on postprandial glycemic control, gastric emptying, and safety parameters in patients with type 2 diabetes on optimized insulin glargine with or without metformin: A randomized, open-label trial. Diabetes Care 2015;38:1263-1273
7. Raccah D, Bretzel RG, Owens D, Riddle M. When basal insulin therapy in type 2 diabetes mellitus is not enough-what next?. Diabetes Metab Res Rev 2007;23:257-264
8. Hermansen K, Davies M, Derezinski T, Martinez Ravn G, Clauson P, Home P. A 26-week, randomized, parallel, treat-to-target trial comparing insulin detemir with NPH insulin as add-on therapy to oral glucose-lowering drugs in insulin-naive people with type 2 diabetes. Diabetes Care 2006;29:1269-1274
9. Raskin P, Allen E, Hollander P, et al.; INITIATE Study Group. Initiating insulin therapy in type 2 diabetes: A comparison of biphasic and basal insulin analogs. Diabetes Care 2005;28:260-265
10. Raskin P, Gylvin T, Weng W, Chaykin L. Comparison of insulin detemir and insulin glargine using a basal-bolus regimen in a randomized, controlled clinical study in patients with type 2 diabetes. Diabetes Metab Res Rev 2009;25: 542-548
11. Rosenstock J, Davies M, Home PD, Larsen J, Koenen C, Schernthaner G. A randomised, 52-week, treat-to-target trial comparing insulin detemir with insulin glargine when administered as add-on to glucose-lowering drugs in insulin-naive people with type 2 diabetes. Diabetologia 2008;51:408-416
12. Rosenstock J, Sugimoto D, Strange P, Stewart JA, Soltes-Rak E, Dailey G. Triple therapy in type 2 diabetes: Insulin glargine or rosiglitazone added to combination therapy of sulfonylurea plus metformin in insulin-naive patients. Diabetes Care 2006;29:554-559
13. Swinnen SG, Dain MP, Aronson R, et al. A 24-week, randomized, treat-to-target trial comparing initiation of insulin glargine once-daily with insulin detemir twice-daily in patients with type 2 diabetes inadequately controlled on oral glucose-lowering drugs. Diabetes Care 2010;33:1176-1178
14. Gutniak M, Orskov C, Holst JJ, Ahrén B, Efendic S. Antidiabetogenic effect of glucagonlike peptide-1 (7-36)amide in normal subjects and patients with diabetes mellitus. N Engl J Med 1992;326:1316-1322
15. Nauck MA, Kleine N, Orskov C, Holst JJ, Willms B, Creutzfeldt W. Normalization of fasting hyperglycaemia by exogenous glucagon-like peptide 1 (7-36 amide) in type 2 (non-insulindependent) diabetic patients. Diabetologia 1993;36:741-744
16. Charbonnel B, Bertolini M, Tinahones FJ, Domingo MP, Davies M. Lixisenatide plus basal insulin in patients with type 2 diabetes mellitus: A meta-analysis. J Diabetes Complications 2014; 28:880-886
17. Raccah D, Lin J, Wang E, et al. Once-daily prandial lixisenatide versus once-daily rapidacting insulin in patients with type 2 diabetes mellitus insufficiently controlled with basal insulin: Analysis of data from five randomized, controlled trials. J Diabetes Complications 2014;28:40-44
18. Riddle MC, Aronson R, Home P, et al. Adding once-daily lixisenatide for type 2 diabetes inadequately controlled by established basal insulin: A 24-week, randomized, placebo-controlled comparison (GetGoal-L). Diabetes Care 2013;36: 2489-2496
19. Riddle MC, Forst T, Aronson R, et al. Adding once-daily lixisenatide for type 2 diabetes inadequately controlled with newly initiated and continuously titrated basal insulin glargine: A 24-week, randomized, placebo-controlled study (GetGoal- Duo 1). Diabetes Care 2013;36:2497-2503
20. Seino Y, Min KW, Niemoeller E, Takami A; EFC10887 GETGOAL-L Asia Study Investigators. Randomized, double-blind, placebocontrolled trial of the once-daily GLP-1 receptor agonist lixisenatide in Asian patients with type 2 diabetes insufficiently controlled on basal insulin with or without a sulfonylurea (GetGoal-L-Asia). Diabetes Obes Metab 2012; 14:910-917
21. Ahrén B, Leguizamo Dimas A, Miossec P, Saubadu S, Aronson R. Efficacy and safety of lixisenatide once-daily morning or evening injections in type 2 diabetes inadequately controlled on metformin (GetGoal-M). Diabetes Care 2013;36:2543-2550
22. Fonseca VA, Alvarado-Ruiz R, Raccah D, Boka G, Miossec P, Gerich JE; EFC6018 GetGoal-Mono Study Investigators. Efficacy and safety of the once-daily GLP-1 receptor agonist lixisenatide in monotherapy: A randomized, double-blind, placebo-controlled trial in patients with type 2 diabetes (GetGoal-Mono). Diabetes Care 2012; 35:1225-1231
23. Yu Pan C, Han P, Liu X, et al. Lixisenatide treatment improves glycaemic control in Asian patients with type 2 diabetes mellitus inadequately controlled on metformin with or without sulfonylurea: A randomized, doubleblind, placebo-controlled, 24-week trial (Get- Goal-M-Asia). Diabetes Metab Res Rev 2014; 30:726-735
24. Rosenstock J, Hanefeld M, Shamanna P, et al. Beneficial effects of once-daily lixisenatide on overall and postprandial glycemic levels without significant excess of hypoglycemia in type 2 diabetes inadequately controlled on a sulfonylurea with or without metformin (GetGoal-S). J Diabetes Complications 2014; 28:386-392
25. Korytkowski M. When oral agents fail: Practical barriers to starting insulin. Int J Obes Relat Metab Disord 2002;26(Suppl. 3):S18-S24
26. Diamant M, Nauck MA, Shaginian R, et al.; 4B Study Group. Glucagon-like peptide 1 receptor agonist or bolus insulin with optimized basal insulin in type 2 diabetes. Diabetes Care 2014; 37:2763-2773
27. Ratner RE, Rosenstock J, Boka G; DRI6012 Study Investigators. Dose-dependent effects of the once-daily GLP-1 receptor agonist lixisenatide in patientswith Type 2 diabetes inadequately controlled with metformin: A randomized, doubleblind, placebo-controlled trial. Diabet Med 2010; 27:1024-1032
28. Gough SC, Bode B, Woo V, et al.; NN9068- 3697 (DUAL-I) trial investigators. Efficacy and safety of a fixed-ratio combination of insulin degludec and liraglutide (IDegLira) compared with its components given alone: Results of a phase 3, open-label, randomised, 26-week, treat-to-target trial in insulin-naive patients with type 2 diabetes. Lancet Diabetes Endocrinol 2014;2:885-893
29. Ahmann AJ, Rodbard HW, Rosenstock J, et al. Efficacy and safety of liraglutide vs. placebo when added to basal insulin analogs in patients with type 2 diabetes (LIRAADD2BASAL). Diabetes 2014;63:A87
30. Rosenstock J, Aronson R, Hanefeld M, et al. Clinical impact of titratable fixed-ratio combination of insulin glargine/lixisenatide vs each component alone in type 2 diabetes inadequately controlled on oral agents: LixiLan-O trial. Presented at the 76th Scientific Sessions of the American Diabetes Association (ADA), 10-14 June 2016, New Orleans, Louisiana, 186-OR
31. Aroda V, Rosenstock J, Wysham C, et al. Efficacy and safety of the insulin glargine/lixisenatide fixed-ratio combination versus insulin glargine in patients with T2DM: The LixiLan-L trial (NCT02058160). Presented at the 76th Scientific Sessions of the American Diabetes Association (ADA), 10-14 June 2016, New Orleans, Louisiana, 238-OR