Monotherapy with the once‐weekly GLP‐1 analogue dulaglutide for 12 weeks in patients with Type 2 diabetes: dose‐dependent effects on glycaemic control in a randomized, double‐blind, placebo‐controlled study

Grunberger, George; Chang, Anna; Sòria, Guadalupe; Botros, Fady T.; Bsharat, Rebhi; Miličević, Zvonko

doi:10.1111/j.1464-5491.2012.03745.x

Cited by 89 publications

(124 citation statements)

References 17 publications

(26 reference statements)

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“…Dulaglutide 1.5 mg and metformin were both associated with a similar weight loss of ;2 kg. These results are in line with those reported in another monotherapy study with dulaglutide, as well as with other GLP-1 receptor agonists and metformin (10,25,26). The effect of dulaglutide on body weight in AWARD-3 was clearly dose dependent and explains the greater weight loss with metformin than with dulaglutide 0.75 mg.…”

Section: Discussionsupporting

confidence: 82%

“…It is noteworthy to observe that in AWARD-3, the magnitude of HbA 1c change associated with both dulaglutide and metformin was smaller than generally reported in other monotherapy trials with the same compounds or other compounds of the GLP-1 receptor agonists class (10,(19)(20)(21)(22). The low mean HbA 1c at randomization (7.6% [60 mmol/mol]) in AWARD-3 was a likely contributor to this observation, as it is well established that interventioninduced HbA 1c changes are confounded by baseline glycemic status (23,24 HbA 1c targets with dulaglutide in AWARD-3 was comparable to that observed in both of these two studies.…”

Section: Discussionmentioning

confidence: 78%

“…In a previous phase 2 dulaglutide monotherapy trial with a longer washout period ($8 weeks), the HbA 1c change from baseline after 12 weeks of treatment with dulaglutide 1.5 mg was greater despite similar baseline HbA 1c to that in AWARD-3 (10). It would be expected that a longer preintervention washout phase enables a more accurate assessment of withingroup treatment effect, due to lack of interference of prestudy treatment on baseline HbA 1c .…”

Section: Discussionmentioning

confidence: 99%

“…Dulaglutide exhibits GLP-1-mediated effects, including glucose-dependent potentiation of insulin secretion, inhibition of glucagon secretion, delay of gastric emptying, and weight loss. In phase 2 studies, dulaglutide demonstrated significant dose-dependent improvements in glycemic control and body weight and a low rate of hypoglycemia (10,11). The most frequent side effects of dulaglutide in these studies were GI related, as observed with other GLP-1 receptor agonists (10)(11)(12).…”

mentioning

confidence: 92%

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Efficacy and Safety of Dulaglutide Monotherapy Versus Metformin in Type 2 Diabetes in a Randomized Controlled Trial (AWARD-3)

Umpiérrez

Tofé²,

Manghi³

et al. 2014

Diabetes Care

267

338

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OBJECTIVECompare the efficacy and safety of monotherapy with dulaglutide, a once-weekly GLP-1 receptor agonist, to metformin-treated patients with type 2 diabetes. The primary objective compared dulaglutide 1.5 mg and metformin on change from baseline glycosylated hemoglobin A 1c (HbA 1c ) at 26 weeks. RESEARCH DESIGN AND METHODSThis 52-week double-blind study randomized patients to subcutaneous dulaglutide 1.5 mg, dulaglutide 0.75 mg, or metformin. Patients (N = 807) had HbA 1c ‡6.5% ( ‡48 mmol/mol) and £9.5% (£80 mmol/mol) with diet and exercise alone or low-dose oral antihyperglycemic medication (OAM) monotherapy; OAMs were discontinued at beginning of lead-in period. RESULTSAt 26 weeks, changes from baseline HbA 1c (least squares [LS] mean 6 SE) were: dulaglutide 1.5 mg, 20.78 6 0.06% (28.5 6 0.70 mmol/mol); dulaglutide 0.75 mg, 20.71 6 0.06% (27.8 6 0.70 mmol/mol); and metformin, 20.56 6 0.06% (26.1 6 0.70 mmol/mol). Dulaglutide 1.5 and 0.75 mg were superior to metformin (LS mean difference): 20.22% (22.4 mmol/mol) and 20.15% (21.6 mmol/mol) (one-sided P < 0.025, both comparisons), respectively. Greater percentages reached HbA 1c targets <7.0% (<53 mmol/mol) and £6.5% (£48 mmol/mol) with dulaglutide 1.5 and 0.75 mg compared with metformin (P < 0.05, all comparisons). No severe hypoglycemia was reported. Compared with metformin, decrease in weight was similar with dulaglutide 1.5 mg and smaller with dulaglutide 0.75 mg. Over 52 weeks, nausea, diarrhea, and vomiting were the most common adverse events; incidences were similar between dulaglutide and metformin. CONCLUSIONSDulaglutide improves glycemic control and is well tolerated as monotherapy in patients with early stage type 2 diabetes.Muscle and liver insulin resistance and b-cell failure represent the core pathophysiologic defects in type 2 diabetes. In addition, there is increasing evidence that the gastrointestinal (GI) tract plays an essential role in the development of carbohydrate intolerance of type 2 diabetes (1). The incretin concept suggests that ingested glucose results in a considerably larger and more sustained insulin secretion compared with glucose administered intravenously due to the release of two intestinal-derived

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Section: Discussionsupporting

confidence: 82%

Section: Discussionmentioning

confidence: 78%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 92%

See 2 more Smart Citations

Efficacy and Safety of Dulaglutide Monotherapy Versus Metformin in Type 2 Diabetes in a Randomized Controlled Trial (AWARD-3)

Umpiérrez

Tofé²,

Manghi³

et al. 2014

Diabetes Care

267

338

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“…This results in a prolonged half-life of approximately 5 days. Dulaglutide exhibits GLP-1-mediated effects, including potentiation of glucosedependent insulin secretion, inhibition of glucagon secretion, delay in gastric emptying, and weight loss (Barrington et al 2011a;Barrington et al 2011b;Glaesner et al 2010;Geiger et al 2012;Grunberger et al 2012;Umpierrez et al 2011).…”

Section: Introductionmentioning

confidence: 99%

Effects of the GLP-1 Receptor Agonist Dulaglutide on the Structure of the Exocrine Pancreas of Cynomolgus Monkeys

et al. 2015

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Clinical and nonclinical studies have implicated glucagon-like peptide-1 (GLP-1) receptor agonist therapy as a risk factor for acute pancreatitis in patients with type 2 diabetes. Therefore, it is critical to understand the effect that dulaglutide, an approved GLP-1 receptor agonist, has on the exocrine pancreas. Dulaglutide 8.15 mg/kg (approximately 500 times the maximum recommended human dose based on plasma exposure) was administered twice weekly for 12 months to cynomolgus monkeys. Serum amylase and lipase activities were measured and 6 sections of each pancreas were examined microscopically. Ductal epithelial cell proliferation was estimated using Ki67 labeling. Dulaglutide administration did not alter serum amylase or lipase activities measured at the end of treatment compared to control values. An extensive histologic evaluation of the pancreas revealed no changes in the acinar or endocrine portions and no evidence of pancreatitis, necrosis, or pancreatic intraepithelial neoplasia. An increase in goblet cells noted in 4 of the 19 treated monkeys was considered an effect of dulaglutide but was not associated with dilation, blockage, or accumulation of mucin in the pancreatic duct. There was no difference in cell proliferation in ductal epithelium between control and dulaglutide-treated monkeys. These data reveal that chronic dosing of nondiabetic primates with dulaglutide does not induce inflammatory or preneoplastic changes in exocrine pancreas.

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Association Between Use of Sodium-Glucose Cotransporter 2 Inhibitors, Glucagon-like Peptide 1 Agonists, and Dipeptidyl Peptidase 4 Inhibitors With All-Cause Mortality in Patients With Type 2 Diabetes

Zheng

Roddick

Aghar-Jaffar

et al. 2018

JAMA

327

238

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Monotherapy with the once‐weekly GLP‐1 analogue dulaglutide for 12 weeks in patients with Type 2 diabetes: dose‐dependent effects on glycaemic control in a randomized, double‐blind, placebo‐controlled study

Abstract: The observed dulaglutide dose-dependent reduction in HbA(1c) and its acceptable safety profile support further clinical development for treatment of Type 2 diabetes.

Cited by 89 publications

References 17 publications

Efficacy and Safety of Dulaglutide Monotherapy Versus Metformin in Type 2 Diabetes in a Randomized Controlled Trial (AWARD-3)

Efficacy and Safety of Dulaglutide Monotherapy Versus Metformin in Type 2 Diabetes in a Randomized Controlled Trial (AWARD-3)

Effects of the GLP-1 Receptor Agonist Dulaglutide on the Structure of the Exocrine Pancreas of Cynomolgus Monkeys

Association Between Use of Sodium-Glucose Cotransporter 2 Inhibitors, Glucagon-like Peptide 1 Agonists, and Dipeptidyl Peptidase 4 Inhibitors With All-Cause Mortality in Patients With Type 2 Diabetes

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