Adverse Effects of GLP-1 Receptor Agonists

Filippatos, Theodosios D.; Panagiotopoulou, Thalia; Elisaf, Moses

doi:10.1900/rds.2014.11.202

Cited by 233 publications

(160 citation statements)

References 187 publications

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“…However, a similar prevalence was observed in the Portuguese HIPOS‐PHARMA study . Although it has been reported that the risk of hypoglycaemia is not a significant concern with new glucose‐lowering drugs, attention is needed when combining these agents with secretagogues or insulin therapy , which was the case in the present study (a higher frequency of hypoglycaemic episodes was observed in the GLP‐1 receptor agonist subgroup, half of whom used insulin at cohort entry).…”

Section: Discussionsupporting

confidence: 81%

Intensive monitoring of adverse drug events associated with the use of new glucose‐lowering drugs: results from an inception cohort study in Portugal

Torre

Guerreiro²,

Longo³

et al. 2019

Diabet. Med.

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Aims To determine the frequency and the time‐course profile of adverse drug events associated with new glucose‐lowering drugs in daily practice and to explore factors potentially associated to these events. Methods An inception cohort study was implemented. Adults with type 2 diabetes mellitus initiating a dipeptidyl peptidase‐4 inhibitor, a glucagon‐like peptide‐1 receptor agonist or a sodium‐glucose co‐transporter‐2 inhibitor were eligible for inclusion. Data were collected through baseline and follow‐up telephone questionnaires, administered at 2 weeks, 3 months and 6 months. Kaplan–Meier curves and log‐rank were computed to compare the time to adverse drug event onset. Cox models were used to explore potential factors associated with adverse drug events. Results A total of 1328 participants were recruited to the study. In all, 1118 adverse drug events were reported (of which 36% were not listed in the summary of product characteristics) by 41% of participants. The median latency time of adverse drug events reported in ≥1% of participants ranged from 0 to 2 days. Glucagon‐like peptide‐1 receptor agonist and sodium‐glucose co‐transporter‐2 inhibitor subgroups were associated with an increased likelihood of adverse drug event reporting when compared with the dipeptidyl peptidase‐4 inhibitor subgroup. A total of 328 glucose‐lowering drugs were withdrawn, more than half as a result of an adverse drug event. Conclusions More than two‐fifths of participants reported an adverse drug event; dipeptidyl peptidase‐4 inhibitors led to the highest proportion of unlabelled adverse drug events. Adverse drug event latency time data show that counselling and adverse drug event management should be proactively addressed from treatment initiation. There should be greater focus on prevalent new users of glucose‐lowering drugs, who were more complex participants in this study in terms of type 2 diabetes disease, as they were more likely to report an adverse drug event than the incident new users.

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Section: Discussionsupporting

confidence: 81%

Intensive monitoring of adverse drug events associated with the use of new glucose‐lowering drugs: results from an inception cohort study in Portugal

Torre

Guerreiro²,

Longo³

et al. 2019

Diabet. Med.

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“…This suggests that GLP-1 analogues may confer some of their effects on appetite through actions on the hypothalamus. The identification of GLP-1 receptors in the area postrema may also explain why nausea is a relatively common side-effect of GLP-1 analogues [16], considering the area postrema has a large role in nausea and vomiting [17]. …”

Section: Discussionmentioning

confidence: 99%

GLP-1 receptors exist in the parietal cortex, hypothalamus and medulla of human brains and the GLP-1 analogue liraglutide alters brain activity related to highly desirable food cues in individuals with diabetes: a crossover, randomised, placebo-controlled trial

et al. 2016

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Aims/hypothesis Liraglutide is a glucagon-like peptide-1 (GLP-1) analogue that has been demonstrated to successfully treat diabetes and promote weight loss. The mechanisms by which liraglutide confers weight loss remain to be fully clarified. Thus, we investigated whether GLP-1 receptors are expressed in human brains and whether liraglutide administration affects neural responses to food cues in diabetic individuals (primary outcome). Methods In 22 consecutively studied human brains, expression of GLP-1 receptors in the hypothalamus, medulla oblongata and parietal cortex was examined using immunohistochemistry. In a randomised (assigned by the pharmacy using a randomisation enrollment table), placebo-controlled, double-blind, crossover trial, 21 individuals with type 2 diabetes (18 included in analysis due to lack or poor quality of data) were treated with placebo and liraglutide for a total of 17 days each (0.6 mg for 7 days, 1.2 mg for 7 days and 1.8 mg for 3 days). Participants were eligible if they had type 2 diabetes and were currently being treated with lifestyle changes or metformin. Participants, caregivers, people doing measurements and/or examinations, and people assessing the outcomes were blinded to the medication assignment. We studied metabolic changes as well as neurocognitive and neuroimaging (fMRI) of responses to food cues at the clinical research centre of Beth Israel Deaconess Medical Center. Results Immunohistochemical analysis revealed the presence of GLP-1 receptors on neurons in the human hypothalamus, medulla and parietal cortex. Liraglutide decreased activation of the parietal cortex in response to highly desirable (vs less desirable) food images (p < 0.001; effect size: placebo 0.53 ± 0.24, liraglutide −0.47 ± 0.18). No significant adverse effects were noted. In a secondary analysis, we observed decreased activation in the insula and putamen, areas involved in the reward system. Furthermore, we showed that increased ratings of hunger and appetite correlated with increased brain activation in response to highly desirable food cues while on liraglutide, while ratings of nausea correlated with decreased brain activation. Conclusions/interpretation For the first time, we demonstrate the presence of GLP-1 receptors in human brains. We also observe that liraglutide alters brain activity related to highly desirable food cues. Our data point to a central mechanism contributing to, or underlying, the effects of liraglutide on metabolism and weight loss. Future studies will be needed to confirm and extend these findings in larger samples of diabetic individuals and/or with the higher doses of liraglutide (3 mg) recently approved for obesity.

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“…Moreover, not only are functional GLP-1R expressed in lung tissue (Romani-Perez et al, 2013;Viby et al, 2013), but they appear to have an important role in regulating surfactant-protein production and lung development in an experimental rat model (Romani-Perez et al, 2013). As a whole, these evidence indicated that GLP-1R agonists appear to be safe and effective against obesity and various parameters of metabolic derangements in patients with no negative effects on the cardiovascular risk on patients (Filippatos, Panagiotopoulou, & Elisaf, 2014). Thus, GLP-1R agonists appear to have a favourable safety profile, but ongoing trials will further assess their effects on the pulmonary components, as well as the mechanism of action.…”

Section: Targeting Obesity With Lifestyle and Pharmacotherapiesmentioning

confidence: 91%

Pathobiological mechanisms underlying metabolic syndrome (MetS) in chronic obstructive pulmonary disease (COPD): clinical significance and therapeutic strategies

Chan

Selemidis

Bozinovski

et al. 2019

Pharmacology & Therapeutics

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a b s t r a c t a r t i c l e i n f oChronic obstructive pulmonary disease (COPD) is a major incurable global health burden and is currently the 4th largest cause of death in the world. Importantly, much of the disease burden and health care utilisation in COPD is associated with the management of its comorbidities (e.g. skeletal muscle wasting, ischemic heart disease, cognitive dysfunction) and infective viral and bacterial acute exacerbations (AECOPD). Current pharmacological treatments for COPD are relatively ineffective and the development of effective therapies has been severely hampered by the lack of understanding of the mechanisms and mediators underlying COPD. Since comorbidities have a tremendous impact on the prognosis and severity of COPD, the 2015 American Thoracic Society/European Respiratory Society (ATS/ERS) Research Statement on COPD urgently called for studies to elucidate the pathobiological mechanisms linking COPD to its comorbidities. It is now emerging that up to 50% of COPD patients have metabolic syndrome (MetS) as a comorbidity. It is currently not clear whether metabolic syndrome is an independent co-existing condition or a direct consequence of the progressive lung pathology in COPD patients. As MetS has important clinical implications on COPD outcomes, identification of disease mechanisms linking COPD to MetS is the key to effective therapy. In this comprehensive review, we discuss the potential mechanisms linking MetS to COPD and hence plausible therapeutic strategies to treat this debilitating comorbidity of COPD.

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Adverse Effects of GLP-1 Receptor Agonists

Cited by 233 publications

References 187 publications

Intensive monitoring of adverse drug events associated with the use of new glucose‐lowering drugs: results from an inception cohort study in Portugal

Intensive monitoring of adverse drug events associated with the use of new glucose‐lowering drugs: results from an inception cohort study in Portugal

GLP-1 receptors exist in the parietal cortex, hypothalamus and medulla of human brains and the GLP-1 analogue liraglutide alters brain activity related to highly desirable food cues in individuals with diabetes: a crossover, randomised, placebo-controlled trial

Pathobiological mechanisms underlying metabolic syndrome (MetS) in chronic obstructive pulmonary disease (COPD): clinical significance and therapeutic strategies

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