A randomized controlled trial comparing the <scp>GLP</scp>‐1 receptor agonist liraglutide to a sulphonylurea as add on to metformin in patients with established type 2 diabetes during Ramadan: the Treat 4 Ramadan Trial

Brady, Emer M; Davies, Melanie J.; Gray, Laura J.; Saeed, Mujahid; Smith, D. B.; Hanif, Wasim; Khunti, Kamlesh

doi:10.1111/dom.12249

Cited by 61 publications

(61 citation statements)

References 30 publications

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“…In the recent LEADER (Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results) trial, liraglutide significantly reduced the risk of the 3 major adverse cardiovascular events (death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke) in patients with DM who were at high risk for cardiovascular events 58. Furthermore, the addition of liraglutide to antidiabetic therapies improved several cardiovascular risk markers in clinical studies 59, 60, 61, 62, 63, 64, 65. However, the mechanism by which liraglutide confers cardiovascular benefits has not been fully elucidated.…”

Section: Discussionmentioning

confidence: 99%

Liraglutide Treatment Reduces Endothelial Endoplasmic Reticulum Stress and Insulin Resistance in Patients With Diabetes Mellitus

Bretón‐Romero

Weisbrod

Feng

et al. 2018

JAHA

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BackgroundPrior studies have shown that nutrient excess induces endoplasmic reticulum (ER) stress in nonvascular tissues from patients with diabetes mellitus (DM). ER stress and the subsequent unfolded protein response may be protective, but sustained activation may drive vascular injury. Whether ER stress contributes to endothelial dysfunction in patients with DM remains unknown.Methods and ResultsTo characterize vascular ER stress, we isolated endothelial cells from 42 patients with DM and 37 subjects without DM. Endothelial cells from patients with DM displayed higher levels of ER stress markers compared with controls without DM. Both the early adaptive response, evidenced by higher phosphorylated protein kinase–like ER eukaryotic initiation factor‐2a kinase and inositol‐requiring ER‐to‐nucleus signaling protein 1 (P=0.02, P=0.007, respectively), and the chronic ER stress response evidenced by higher C/EBPα‐homologous protein (P=0.02), were activated in patients with DM. Higher inositol‐requiring ER‐to‐nucleus signaling protein 1 activation was associated with lower flow–mediated dilation, consistent with endothelial dysfunction (r=0.53, P=0.02). Acute treatment with liraglutide, a glucagon‐like peptide 1 receptor agonist, reduced p‐inositol‐requiring ER‐to‐nucleus signaling protein 1 (P=0.01), and the activation of its downstream target c‐jun N‐terminal kinase (P=0.025) in endothelial cells from patients with DM. Furthermore, liraglutide restored insulin‐stimulated endothelial nitric oxide synthase activation in patients with DM (P=0.019).ConclusionsIn summary, our data suggest that ER stress contributes to vascular insulin resistance and endothelial dysfunction in patients with DM. Further, we have demonstrated that liraglutide ameliorates ER stress, decreases c‐jun N‐terminal kinase activation and restores insulin‐mediated endothelial nitric oxide synthase activation in endothelial cells from patients with DM.

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Section: Discussionmentioning

confidence: 99%

Liraglutide Treatment Reduces Endothelial Endoplasmic Reticulum Stress and Insulin Resistance in Patients With Diabetes Mellitus

Bretón‐Romero

Weisbrod

Feng

et al. 2018

JAHA

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“…Subjects in this trial had suboptimal glycaemic control at baseline. Previously, Brady et al investigated the effect of liraglutide versus sulphonylurea on glycaemic control at 3 and 12 weeks post‐Ramadan, but not during Ramadan 28. Although more subjects treated with liraglutide plus metformin (26.7%) than those treated with sulphonylurea plus metformin (10.3%) achieved the primary outcome of HbA1c <7.0% (53 mmol/mol), no weight gain and no severe hypoglycaemic events 12 weeks post‐Ramadan, statistical significance was not attained (p = 0.06) because the trial was underpowered.…”

Section: Discussionmentioning

confidence: 99%

Efficacy and safety of liraglutide compared to sulphonylurea during Ramadan in patients with type 2 diabetes (LIRA‐Ramadan): a randomized trial

Azar

Echtay

Bebakar

et al. 2016

Diabetes Obesity Metabolism

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AimsCompare effects of liraglutide 1.8 mg and sulphonylurea, both combined with metformin, on glycaemic control in patients with type 2 diabetes (T2D) fasting during Ramadan.Materials and methodsIn this up to 33‐week, open‐label, active‐controlled, parallel‐group trial, adults [glycated haemoglobin (HbA1c) 7%‐10% (53‐86 mmol/mol); body mass index ≥20 kg/m2; intent to fast] were randomized (1:1) ≥10 weeks before Ramadan to either switch to once‐daily liraglutide (final dose 1.8 mg) or continue pre‐trial sulphonylurea at maximum tolerated dose, both with metformin. Primary endpoint: change in fructosamine, a validated marker of short‐term glycaemic control, during Ramadan.ResultsSimilar reductions in fructosamine levels were observed for both groups during Ramadan [liraglutide (−12.8 µmol/L); sulphonylurea (−16.4 µmol/L); estimated treatment difference (ETD) 3.51 µmol/L (95% CI: −5.26; 12.28); p = 0.43], despite lower fructosamine levels in the liraglutide group at start of Ramadan. Fewer documented symptomatic hypoglycaemic episodes were reported in liraglutide‐treated (2%, three subjects) versus sulphonylurea‐treated patients (11%, 18 subjects). No severe hypoglycaemic episodes were reported by either group. Body weight decreased more during Ramadan with liraglutide (ETD: −0.54 kg; 95% CI: −0.94;−0.14; p = 0.0091). The proportion of patients reporting adverse events was similar between groups. Liraglutide led to greater HbA1c reduction [ETD: −0.59% (−6.40 mmol/mol), 95% CI: −0.79; −0.38%; −8.63; −4.17 mmol/mol; p < 0.0001].ConclusionsDespite lower fructosamine levels and body weight at the beginning of Ramadan, use of liraglutide showed similar glycaemic improvements, fewer hypoglycaemic episodes and greater body weight reduction compared with sulphonylurea. LIRA‐Ramadan provides evidence for liraglutide being safe and efficacious for management of T2D during Ramadan fasting.

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“…As for the incretin hormones, analogues of GLP-1 do not require titration, as they do not induce hypoglycaemia, but if associated with sulphonylureas or insulin, they may increase the hypoglycaemic effect (Brady et al, 2014). DDP-IV inhibitors do not require titration thanks to their low propensity to induce hypoglycaemia, but if associated with sulfonylureas or insulin they may potentiate the hypoglycaemic effect.…”

Section: Adjusting the Hypoglycaemic Therapy For Diabetic Patients Dumentioning

confidence: 99%

Diabetes Mellitus and Ramadan: Physiopathological, Clinical and Therapeutic Aspects

Urso

Brucculeri

Firenze³

et al. 2017

IJANHS

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Fasting from dawn to sunset during Ramadan is one of the five pillars of Islam. A significant number of diabetic patients insist on fasting during Ramadan against the recommendations of their physicians. Fasting in diabetic subjects may be associated with increased risk of hypoglycemia and hyperglycemia, diabetic ketoacidosis, dehydration and thrombosis. Patients with uncontrolled diabetes mellitus are predisposed to major metabolic risks. Another problem is the reluctance of diabetic patients in taking their medications during the fast; therefore the timing and the dosage of anti-diabetic drugs must be adapted for each patient. It is important for diabetic patients who wish to fast during Ramadan to effect the necessary preparation to approach the fasting as safely as possible. Up to now, the management of these patients is a challenge for healthcare professionals. The aim of this minireview is that to offer a simple guide for management of Muslim diabetic patient during Ramadan.

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A randomized controlled trial comparing the GLP‐1 receptor agonist liraglutide to a sulphonylurea as add on to metformin in patients with established type 2 diabetes during Ramadan: the Treat 4 Ramadan Trial

Cited by 61 publications

References 30 publications

Liraglutide Treatment Reduces Endothelial Endoplasmic Reticulum Stress and Insulin Resistance in Patients With Diabetes Mellitus

Liraglutide Treatment Reduces Endothelial Endoplasmic Reticulum Stress and Insulin Resistance in Patients With Diabetes Mellitus

Efficacy and safety of liraglutide compared to sulphonylurea during Ramadan in patients with type 2 diabetes (LIRA‐Ramadan): a randomized trial

Diabetes Mellitus and Ramadan: Physiopathological, Clinical and Therapeutic Aspects

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