Three-year data from 5 HARMONY phase 3 clinical trials of albiglutide in type 2 diabetes mellitus: Long-term efficacy with or without rescue therapy

Home, Philip; Åhrén, Bo; Reusch, Jane E.B.; Rendell, Marc; Weissman, Peter N.; Cirkel, Deborah T.; Miller, Diane; Ambery, Philip; Carr, Maria; Nauck, Michael A.

doi:10.1016/j.diabres.2017.06.013

Cited by 33 publications

(18 citation statements)

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“…It has been reported that Albiglutide can reduce myocardial infarct size, and improve left ventricular function following myocardial ischemia, as compared with placebo in rat models . Moreover, in a phase III trial with Albiglutide, an increase in mean heart rate of 1–2 beats per minute was observed, compared with the all control groups . In a preclinical study, the protection role of exendin‐4 in cardiovascular diseases has also been confirmed by our lab .…”

Section: Discussionsupporting

confidence: 73%

Antidiabetic Effect of Abextide, a Long‐Acting Exendin‐4 Analogue in Cynomolgus Monkeys

Niu

Wang

Lau

et al. 2018

Adv Healthcare Materials

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Abextide, synthesized by conjugating an albumin‐binding moiety—truncated Evans blue—to glucagon‐like peptide 1 receptor (GLP‐1R) agonist exendin‐4, shows extended drug release and enhanced hypoglycemic effect in diabetic mice. The aim of this study is to evaluate the pharmacodynamics of Abextide in nonhuman primates. Two batches of elderly cynomolgus monkeys with naturally occurring diabetes are used for this study. During the whole experiment period, no abnormalities such as swelling at the injection site, lethargy, or hypoglycemia are observed in all animals. The monkeys in the Abextide group lose appetite after drug administration and then recover over time. In the single dose treatment, at day 1 and day 3 after treatment, decreased plasma glucose level is observed in the Abextide‐treated group but not in placebo or Albiglutide‐treated group. For monkeys that receive two doses of drug, the blood glucose level in all subjects in Abextide group decreases rapidly upon drug administration and return to a plateau by day 3. A similar pattern of response is seen after the second dose administration. The delayed drug release and hypoglycemic effect of Abextide make it potentially useful as an antidiabetic drug for weekly subcutaneous administration.

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Section: Discussionsupporting

confidence: 73%

Antidiabetic Effect of Abextide, a Long‐Acting Exendin‐4 Analogue in Cynomolgus Monkeys

Niu

Wang

Lau

et al. 2018

Adv Healthcare Materials

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“…There are also 3-year data for exenatide across three of the DURATION trials (DURATION-1, -2 and -3), and pooled data from these trials have demonstrated that reductions in HbA 1c were maintained at 1.1% from baseline at year 3 [ 11 ]. Similarly, pooled data from five of the HARMONY studies have demonstrated that albiglutide reduced HbA 1c by up to 0.92% at the end of year 3 [ 12 ]. Cross-trial efficacy comparisons should always be made with caution.…”

Section: Discussionmentioning

confidence: 99%

Liraglutide and Glycaemic Outcomes in the LEADER Trial

et al. 2018

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IntroductionThe LEADER trial was a cardiovascular (CV) outcomes trial in patients with type 2 diabetes at high CV risk that compared liraglutide (n = 4668) with placebo (n = 4672) using a primary composite endpoint of 3-point major adverse CV events. The objective of this post hoc analysis was to investigate glycaemic outcomes across both treatment groups.MethodsGlycated haemoglobin (HbA1c) was measured at randomisation, month 3, month 6 and every 6 months thereafter. Cox regression was used to analyse time to a composite endpoint of glycaemic deterioration, defined as a specified change in HbA1c or a substantial intensification of insulin or oral antihyperglycaemic drug (OAD). The individual components of the composite were also analysed.ResultsBaseline characteristics, including insulin and OAD use, were balanced between treatment groups. HbA1c decreased from baseline in both groups, but the reduction was greater with liraglutide [estimated treatment difference at month 36: − 0.40%; 95% confidence interval (CI) − 0.45, − 0.34] despite the addition of more OADs and higher insulin use in the placebo group. Fewer of the patients treated with liraglutide (n = 3202, 68.6%) experienced glycaemic deterioration compared with those administered the placebo (n = 3988, 85.4%; average hazard ratio: 0.50; 95% CI 0.48, 0.53; p < 0.001). Analysis of the individual components showed similar results (both p < 0.001).ConclusionsType 2 diabetes patients at high risk of CV events who were treated with liraglutide achieved greater reductions in HbA1c, had a lower risk of hypoglycaemia and presented less glycaemic deterioration than similar patients who received the placebo. Nonetheless, progressive loss of glycaemic control occurred in both groups.Trial RegistrationClinicalTrials.gov, NCT01179048.FundingNovo Nordisk.Plain Language SummaryPlain language summary available for this article.Electronic supplementary materialThe online version of this article (10.1007/s13300-018-0524-z) contains supplementary material, which is available to authorized users.

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“…Safety and cardiorenal outcome data have been published for albiglutide [115,116]. The cardiovascular endpoint data on albiglutide (HARMONY outcomes trial [117]) were analysed and published in 2018.…”

Section: Glp-1 Receptor Agonistsmentioning

confidence: 99%

Therapy of Type 2 Diabetes

Landgraf

Aberle

Birkenfeld

et al. 2019

Exp Clin Endocrinol Diabetes

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The practical recommendations of the German Diabetes Society/ Deutsche Diabetes Gesellschaft (DDG) together with the German Society for Internal Medicine/Deutschen Gesellschaft für Innere Medizin (DGIM) are based on the contents of the National Treatment Guideline (Nationale Versorgungsleitlinie NVL) "Therapy of Type 2 Diabetes" [1]. The modifications in therapy and their justifications made in the present DDG practical recommendations were updated on the basis of new randomized controlled trials (RCTs) and meta-analyses and were consented by the DDG and the DGIM. Definition of Type 2 DiabetesType 2 diabetes is a chronic, very heterogeneous, multi-factorial, progressive disease characterized by inherited and acquired insulin resistance and qualitative and quantitative insulin secretion disturbances.Influenceable and uninfluenceable risk factors for type 2 diabetes are listed in the "Risk factors for type 2 diabetes" infobox. Therapeutic goalsIn the present recommendations, target ranges are identified which -with varying levels of strengths of evidence -inform the physician and the patient on which target range/target value should be aimed for according to current medical knowledge based on evidence and consensus. The main objective remains to set individual therapy goals primarily together with the patient and possibly his or her relatives and agreeing them optimally in writing on a quarterly basis (e. g. in the Health Passport Diabetes). General and specific therapeutic goalsThe therapeutic goals of people with type 2 diabetes depend on patient preference, comorbidity, duration of the disease, age and life expectancy, quality of life, cultural conditions, psychosocial circumstances and possibilities as well as abilities of the persons S73This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.

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Three-year data from 5 HARMONY phase 3 clinical trials of albiglutide in type 2 diabetes mellitus: Long-term efficacy with or without rescue therapy

Cited by 33 publications

References 32 publications

Antidiabetic Effect of Abextide, a Long‐Acting Exendin‐4 Analogue in Cynomolgus Monkeys

Antidiabetic Effect of Abextide, a Long‐Acting Exendin‐4 Analogue in Cynomolgus Monkeys

Liraglutide and Glycaemic Outcomes in the LEADER Trial

Therapy of Type 2 Diabetes

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