Efficacy and Safety of LixiLan, 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

被引:66
作者
Rosenstock, Julio [1 ]
Diamant, Michaela [2 ]
Aroda, Vanita R. [3 ]
Silvestre, Louise [4 ]
Souhami, Elisabeth [4 ]
Zhou, Tianyue [5 ]
Perfetti, Riccardo [5 ]
Fonseca, Vivian [6 ]
机构
[1] Dallas Diabet & Endocrine Ctr Med City, Dallas, TX 75230 USA
[2] Vrije Univ Amsterdam, Med Ctr, Amsterdam, Netherlands
[3] MedStar Hlth Res Inst, Hyattsville, MD USA
[4] Sanofi, Paris, France
[5] Sanofi, Bridgewater, NJ USA
[6] Tulane Univ, Hlth Sci Ctr, New Orleans, LA 70118 USA
基金
美国国家卫生研究院;
关键词
TO-TARGET TRIAL; GLUCOSE-LOWERING DRUGS; RECEPTOR AGONIST LIXISENATIDE; PLACEBO-CONTROLLED TRIAL; ONCE-DAILY LIXISENATIDE; OPEN-LABEL TRIAL; BASAL INSULIN; DOUBLE-BLIND; GLYCEMIC CONTROL; NAIVE PATIENTS;
D O I
10.2337/dc16-0046
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
OBJECTIVE This study assessed the efficacy and safety of LixiLan, a fixed-ratio, titratable, combination of 2 units insulin glargine (Gla-100) and 1 mu g lixisenatide administered once daily via a single pen, versus Gla-100 in insulin-naive type 2 diabetes on metformin. RESEARCH DESIGN AND METHODS Participants were randomized to once-daily LixiLan (n = 161) or Gla-100 (n = 162) for 24 weeks, while continuing metformin. LixiLan and Gla-100 were started at 10 units/5 mg and 10 units, respectively, and titrated based on the Gla-100 requirement according to fasting plasma glucose levels. The primary objective was to test noninferiority (upper bound of the 95% CI <= 0.4%) of LixiLan in reducing HbA(1c); if met, statistical superiority was tested. Secondary objectives included body weight changes, hypoglycemia, and safety. RESULTS Baseline characteristics (mean age 57 years, diabetes duration 6-7 years, BMI 32 kg/m(2)) were similar between groups. At week 24, mean HbA1c was reduced from 8.0% (64 mmol/mol) at baseline to 6.3% (45 mmol/mol) and 6.5% (48 mmol/mol) with LixiLan and Gla-100, respectively, establishing statistical noninferiority and superiority of LixiLan (least-squaredmean [95% CI] difference: -0.17% [-0.31, -0.04] {-1.9mmol/mol [-3.4, -0.4]}; P = 0.01). HbA(1c) < 7.0% (< 53 mmol/mol) was achieved in 84% and 78% of participants (nonsignificant), respectively. LixiLan improved 2-h postmeal plasma glucose versus Gla-100 (least-squared mean difference: -3.17 mmol/L [-57 mg/dL]; P < 0.0001). Body weight was reduced with LixiLan (-1 kg) and increased with Gla-100 (+0.5 kg; P < 0.0001), with no increase in hypoglycemic events (similar to 25% in each group). The incidence of nausea (7.5%) and vomiting (2.5%) was low with LixiLan. CONCLUSIONS LixiLan achieved statistically significant reductions to near-normal HbA1c levels with weight loss and no increased hypoglycemic risk, compared with insulin glargine alone, and a low incidence of gastrointestinal adverse events in type 2 diabetes inadequately controlled on metformin.
引用
收藏
页码:1579 / 1586
页数:8
相关论文
共 30 条
[1]  
Ahmann AJ, 2014, DIABETES, V63, pA87
[2]   Efficacy and Safety of Lixisenatide Once-Daily Morning or Evening Injections in Type 2 Diabetes Inadequately Controlled on Metformin (GetGoal-M) [J].
Ahren, Bo ;
Leguizamo Dimas, Aniceto ;
Miossec, Patrick ;
Saubadu, Stephane ;
Aronson, Ronnie .
DIABETES CARE, 2013, 36 (09) :2543-2550
[3]  
Aroda V, 2016, 76 SCI SESS AM DIAB
[4]   Insulin glargine versus sitagliptin in insulin-naive patients with type 2 diabetes mellitus uncontrolled on metformin (EASIE): a multicentre, randomised open-label trial [J].
Aschner, Pablo ;
Chan, Juliana ;
Owens, David R. ;
Picard, Sylvie ;
Wang, Edward ;
Dain, Marie-Paule ;
Pilorget, Valerie ;
Echtay, Akram ;
Fonseca, Vivian .
LANCET, 2012, 379 (9833) :2262-2269
[5]   New insulin glargine 300 U/ml compared with glargine 100 U/ml in insulin-naive people with type 2 diabetes on oral glucose-lowering drugs: a randomized controlled trial (EDITION 3) [J].
Bolli, G. B. ;
Riddle, M. C. ;
Bergenstal, R. M. ;
Ziemen, M. ;
Sestakauskas, K. ;
Goyeau, H. ;
Home, P. D. .
DIABETES OBESITY & METABOLISM, 2015, 17 (04) :386-394
[6]   Lixisenatide plus basal insulin in patients with type 2 diabetes mellitus: a meta-analysis [J].
Charbonnel, Bernard ;
Bertolini, Monica ;
Tinahones, Francisco J. ;
Puig Domingo, Manuel ;
Davies, Melanie .
JOURNAL OF DIABETES AND ITS COMPLICATIONS, 2014, 28 (06) :880-886
[7]   Glucagon-Like Peptide 1 Receptor Agonist or Bolus Insulin With Optimized Basal Insulin in Type 2 Diabetes [J].
Diamant, Michaela ;
Nauck, Michael A. ;
Shaginian, Rimma ;
Malone, James K. ;
Cleall, Simon ;
Reaney, Matthew ;
de Vries, Danielle ;
Hoogwerf, Byron J. ;
MacConell, Leigh ;
Wolffenbuttel, Bruce H. R. .
DIABETES CARE, 2014, 37 (10) :2763-2773
[8]   An analysis of early insulin glargine added to metformin with or without sulfonylurea: impact on glycaemic control and hypoglycaemia [J].
Fonseca, V. ;
Gill, J. ;
Zhou, R. ;
Leahy, J. .
DIABETES OBESITY & METABOLISM, 2011, 13 (09) :814-822
[9]   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) [J].
Fonseca, Vivian A. ;
Alvarado-Ruiz, Ricardo ;
Raccah, Denis ;
Boka, Gabor ;
Miossec, Patrick ;
Gerich, John E. .
DIABETES CARE, 2012, 35 (06) :1225-1231
[10]   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 [J].
Gough, Stephen C. L. ;
Bode, Bruce ;
Woo, Vincent ;
Rodbard, Helena W. ;
Linjawi, Sultan ;
Poulsen, Pernille ;
Damgaard, Lars H. ;
Buse, John B. .
LANCET DIABETES & ENDOCRINOLOGY, 2014, 2 (11) :885-893