iGlarLixi: A Fixed-Ratio Combination of Insulin Glargine 100 U/mL and Lixisenatide for the Treatment of Type 2 Diabetes

Objective: To review the safety and efficacy of iGlarLixi, a titratable fixed-ratio combination of insulin glargine 100 U/mL (iGlar) and lixisenatide, a glucagon-like peptide-1 receptor agonist. Data Sources: A literature search of MEDLINE for all English-language primary articles through June 2016, using the terms LixiLan, iGlarLixi and insulin glargine and lixisenatide, and a search of abstracts presented at the 2016 Scientific Sessions of the American Diabetes Association were performed. Study Selection and Data Extraction: All studies assessing the efficacy and/or safety of iGlarLixi were evaluated. Data Synthesis: iGlarLixi has been approved in the United States for glycemic control in people with type 2 diabetes (T2D) inadequately controlled with basal insulin (<60 U/d) or lixisenatide. In clinical trials, iGlarLixi was associated with significantly greater reductions from baseline in glycated hemoglobin A1C (A1C) than iGlar or lixisenatide alone. Reductions in postprandial glucose were also greater with iGlarLixi than with iGlar or lixisenatide. iGlarLixi was weight neutral compared with the weight gain with iGlar and loss with lixisenatide alone, and there was no increase in hypoglycemia with iGlarLixi compared with iGlar despite the greater A1C reduction. Gastrointestinal events, frequently associated with lixisenatide, were less common with iGlarLixi. Potential drawbacks of iGlarLixi include reduced flexibility in dosing and the absence of long-term efficacy and safety data. Conclusions: iGlarLixi is a titratable fixed-ratio combination that shows improved efficacy and comparable or improved safety outcomes relative to its separate constituents, offering an alternative approach to intensification of therapy in T2D.

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EFFICACY AND SAFETY OF IGLARLIXI IN HISPANICS AND NON-HISPANIC WHITES WITH TYPE 2 DIABETES

Endocrine Practice ◽

10.4158/ep-2018-0615 ◽

2019 ◽

Vol 25 (11) ◽

pp. 1091-1100

Author(s):

Pablo F. Mora ◽

Jason Chao ◽

Aramesh Saremi ◽

Terry A. Dex ◽

Michelle Roberts ◽

...

Keyword(s):

Type 2 Diabetes ◽

Insulin Glargine ◽

Glycated Hemoglobin ◽

Fixed Ratio ◽

Density Lipoprotein ◽

Postprandial Glucose ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1 ◽

Hispanic White

Objective: Type 2 diabetes (T2D) is more common in Hispanic than non-Hispanic white (NHW) populations worldwide, and ethnicity, among other factors, may affect response to therapy. The efficacy and safety of insulin glargine 100 units/mL (iGlar) and the fixed-ratio combination of iGlar and the glucagon-like peptide 1 receptor agonist lixisenatide (iGlarLixi) was assessed in Hispanic and NHW patients with T2D from 25 countries. Methods: In this post hoc analysis, data from two 30-week randomized controlled trials comparing iGlar and iGlarLixi in patients with T2D uncontrolled on basal insulin ± oral antidiabetes drugs (OADs; LixiLan-L: NCT02058160) or uncontrolled on metformin ± OADs (LixiLan-O: NCT02058147) were evaluated. Results: Of the 1,512 patients included across trials, 301 were Hispanic and 1,211 NHW. Compared with iGlar, iGlarLixi resulted in greater reductions in glycated hemoglobin (A1C) and 2-hour postprandial glucose and a higher proportion of patients at target A1C <7.0% (<53 mmol/mol), regardless of ethnicity. Among NHWs from the LixiLan-L trial, documented symptomatic hypoglycemia (plasma glucose ≤70 mg/dL) rates were higher with iGlar compared with iGlarLixi ( P = .06), whereas this trend was reversed among Hispanics ( P = .07). Nevertheless, in both trials, a greater proportion of patients taking iGlarLixi than iGlar reached the composite efficacy endpoints of target A1C without hypoglycemia and target A1C without weight gain, regardless of ethnicity. Conclusion: These results indicate that iGlarLixi is a viable therapeutic option for both Hispanic and NHW patients with T2D, as it is efficacious without a significant increase in hypoglycemia, irrespective of ethnicity. Abbreviations: A1C = glycated hemoglobin; BMI = body mass index; FPG = fasting plasma glucose; FRC = fixed-ratio combination; GLP-1 RA = glucagon-like peptide 1 receptor agonist; HDL-C = high-density-lipoprotein cholesterol; iGlar = insulin glargine; iGlarLixi = insulin glargine + lixisenatide; LDL-C = low-density-lipoprotein cholesterol; NHW = non-Hispanic white; OAD = oral antidiabetes drug; PPG = postprandial glucose; T2D = type 2 diabetes

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Advances in Basal Insulin Therapy

Journal of Pharmacy Technology ◽

10.1177/8755122516667128 ◽

2016 ◽

Vol 32 (6) ◽

pp. 260-268

Author(s):

Jennifer Goldman ◽

John R. White

Keyword(s):

Type 2 Diabetes ◽

Insulin Glargine ◽

Basal Insulin ◽

Data Extraction ◽

The United States ◽

Insulin Degludec ◽

Study Selection ◽

Meta Analyses

Objective: To review 2 new basal insulin analogs that have been approved in the United States for use in type 1 and type 2 diabetes—insulin glargine 300 units/mL and insulin degludec 100 units/mL and 200 units/mL. Data Sources: PubMed was searched using the terms “insulin glargine 300 units/mL,” “Gla-300,” “insulin degludec,” “IDeg,” “insulin degludec 200 units/mL,” and “insulin degludec 100 units/mL” for articles published between 1995 and May 2016. Study Selection and Data Extraction: Clinical trials, meta-analyses and subanalyses were identified; review articles were excluded. Relevant citations from identified articles were also reviewed. Data Synthesis: The new basal insulins, insulin glargine 300 units/mL and insulin degludec 100 units/mL and 200 units/mL, have improved pharmacokinetic and pharmacodynamic profiles compared to insulin glargine 100 units/mL. All demonstrate longer durations of action, beyond 24 hours, and less variability. These improved profiles translate into comparable A1C reductions and comparable, or improved, levels of hypoglycemia compared to insulin glargine 100 units/mL. Conclusions: These benefits may lead to improved glycemic control in a range of patients with type 1 and type 2 diabetes with true once-daily dosing.

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Oral Semaglutide: First-in-Class Oral GLP-1 Receptor Agonist for the Treatment of Type 2 Diabetes Mellitus

Annals of Pharmacotherapy ◽

10.1177/1060028019889064 ◽

2019 ◽

Vol 54 (5) ◽

pp. 478-485 ◽

Cited By ~ 2

Author(s):

Kevin Cowart

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Receptor Agonist ◽

English Language ◽

Data Extraction ◽

Pharmacological Therapy ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1

Objective:The purpose of this article is to review the pharmacological characteristics and clinical evidence of oral semaglutide for the treatment of type 2 diabetes mellitus (T2DM). Data Sources: A MEDLINE/PubMed search was conducted between January 1, 2005, and September 30, 2019. Search terms included semaglutide, glucagon-like peptide 1 receptor agonist, GLP-1 receptor agonist, and type 2 diabetes. Study Selection and Data Extraction Quantification: The following study designs were included in the analysis: systematic review and/or meta-analyses, clinical trial, or observational study design. Narrative reviews were excluded. Articles were included only if they were published in the English language or evaluated oral semaglutide with regard to pharmacology, pharmacokinetics, safety, and efficacy in humans. Data Synthesis: Oral semaglutide has been Food and Drug Administration approved for the treatment of T2DM as an adjunct to diet and exercise. Oral semaglutide has been shown to result in an absolute hemoglobin A1C reduction between −0.5% and −1.5% and weight reductions between −1 and −4.7 kg. Oral semaglutide has been shown to be noninferior to placebo for cardiovascular (CV) safety although additional CV outcomes trials are ongoing. Adverse effects appear to be similar to those of other glucagon-like peptide-1 receptor agonists and are gastrointestinal in nature. Relevance to Patient Care and Clinical Practice: Oral semaglutide may be appropriate as second- or third-line add-on therapy for patients with T2DM who are not meeting treatment goals on metformin and are overweight and reluctant to use an injectable drug. Conclusions: Oral semaglutide appears safe and effective as monotherapy and add-on pharmacological therapy for the treatment of T2DM.

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Semaglutide: The Newest Once-Weekly GLP-1 RA for Type 2 Diabetes

Annals of Pharmacotherapy ◽

10.1177/1060028018784583 ◽

2018 ◽

Vol 52 (12) ◽

pp. 1224-1232 ◽

Cited By ~ 3

Author(s):

Rhianna M. Tuchscherer ◽

Angela M. Thompson ◽

Jennifer M. Trujillo

Keyword(s):

Type 2 Diabetes ◽

English Language ◽

Data Extraction ◽

Published Data ◽

Data Synthesis ◽

Language Studies ◽

Study Selection ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1

Objective: To review efficacy and safety of the glucagon-like peptide-1 receptor agonist (GLP-1 RA) semaglutide for type 2 diabetes (T2D). Data Sources: A literature search of PubMed/MEDLINE and EMBASE using the term semaglutide was completed through April 2018. A search of clinicaltrials.gov was also conducted. Study Selection and Data Extraction: English-language studies assessing the efficacy and/or safety of semaglutide were evaluated. Data Synthesis: Semaglutide is a newly approved GLP-1 RA for the treatment of T2D. Administered once weekly at a dose of 0.5 or 1 mg, it has been compared with placebo, sitagliptin, insulin glargine, a combination of oral antidiabetic therapies, and 2 GLP-1 RAs, exenatide ER and dulaglutide, and demonstrated greater efficacy compared with these therapies. Published data from studies ranging from 30 to 104 weeks duration demonstrate efficacy with decreases in hemoglobin A1C (A1C) ranging from 1.1% to 2.2%. Studies show reductions in weight from 1.4 to 6.5 kg. Semaglutide demonstrated a reduction in the composite outcome of cardiovascular (CV) death, nonfatal myocardial infarction, or nonfatal stroke compared with placebo in patients at high risk of CV events (hazard ratio = 0.74; P = 0.02). Common adverse effects include nausea, vomiting, and diarrhea as seen with other GLP-1 RAs. Relevance to Patient Care and Clinical Practice: Semaglutide represents an attractive GLP-1 RA considering its A1C and weight reduction. It provides patient convenience and high patient satisfaction. Conclusions: Semaglutide is an appealing option for the treatment of T2D as a once-weekly GLP-1 RA with established glycemic, CV, and weight benefits.

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Effectiveness of IGlarLixi, a Fixed-Ratio Combination of Insulin Glargine 100 U/mL and Lixisenatide, in People with Type 2 Diabetes

Diabetes Therapy ◽

10.1007/s13300-021-01128-5 ◽

2021 ◽

Author(s):

János Tibor Kis ◽

Gábor Nagy ◽

Gábor Kovacs

Keyword(s):

Type 2 Diabetes ◽

Insulin Glargine ◽

Fixed Ratio

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Durable Effects of iGlarLixi Up to 52 Weeks in Type 2 Diabetes: The LixiLan-G Extension Study

10.2337/figshare.13369553 ◽

2021 ◽

Author(s):

Lawrence Blonde ◽

Julio Rosenstock ◽

Juan Frias ◽

Andreas L. Birkenfeld ◽

Elisabeth Niemoeller ◽

...

Keyword(s):

Type 2 Diabetes ◽

Fixed Ratio ◽

Efficacy And Safety ◽

Open Label ◽

Once Daily ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1 ◽

Design And Methods ◽

Extension Period

Objective <a>In the LixiLan-G trial, switching to iGlarLixi, a once-daily titratable fixed-ratio combination of insulin glargine </a>100 units/mL and the glucagon-like peptide-1 receptor agonist (GLP-1 RA) lixisenatide, improved glucose control in type 2 diabetes (T2D) uncontrolled with GLP-1 RAs over 26 weeks versus continuing prior GLP-1 RA. A prespecified, 26-week, single-arm extension of LixiLan-G aimed to determine the durability of iGlarLixi efficacy and safety over 52 weeks. Research Design and Methods Participants with T2D uncontrolled by GLP-1 RAs (HbA1c 7–9 % [53–75 mmol/mol]) were initially randomized to switch to iGlarLixi or continue prior GLP-1 RA. Those randomized to iGlarLixi who completed the 26-week primary endpoint period could continue iGlarLixi open-label treatment over a 26-week extension to assess durability of efficacy and safety. Results Glycemic control achieved with iGlarLixi at week 26 (mean HbA1c 6.7 % [50 mmol/mol]) was maintained at week 52 (mean HbA1c 6.7 % [50 mmol/mol]; mean ± standard deviation change from baseline at week 52: −1.0 ± 0.9 % [11 ± 10 mmol/mol]). Proportions of participants reaching HbA1c <7 % (53 mmol/mol) with iGlarLixi were similar at week 26 (62%) and 52 (64%), as were those reaching this target without documented symptomatic (<3.0 mmol/L) hypoglycemia (57% and 58%). Safety of iGlarLixi was similar at weeks 26 and 52, with low rates of documented symptomatic hypoglycemia and gastrointestinal events. Conclusions The efficacy and safety of iGlarLixi at the end of the 26-week randomized treatment period was maintained over the 26-week extension period in the LixiLan-G trial.

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