Efficacy of Glucagon-Like Peptide-1 Receptor Agonists in the Weight Loss Among Obese Individuals: A Systematic Review

Aldahash, Raed

doi:10.14740/jem745

Cited by 4 publications

(3 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This may partly explain the impeded clinical success. However, our results for NN1177 are consistent with other studies demonstrating weight loss and related beneficial outcomes for glucagon and GLP-1 RAs [2, 9, 16, 17].…”

Section: Discussionsupporting

confidence: 92%

“…GLP-1 reduces body weight by decreasing energy intake through a reduction in appetite and induction of satiety [15]. As such, GLP-1 receptor agonists (GLP-1 RAs) have proven benefits on body weight and the complications associated with obesity [2, 16, 17]. GLP-1 RAs have been shown to reduce body weight [18, 19], and two members of the drug class, liraglutide and semaglutide, are approved for weight management.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Glucagon/GLP-1 receptor co-agonist NNC9204-1177 reduced body weight in adults with overweight or obesity but was associated with safety issues

Friedrichsen

Nygård

Endahl

et al. 2022

Preprint

View full text Add to dashboard Cite

Glucagon/glucagon-like peptide-1 (GLP-1) receptor co-agonists may provide greater weight loss than agonists targeting the GLP-1 receptor alone. We report results from three phase 1 trials investigating the glucagon/GLP-1 receptor co-agonist NNC9204-1177 (NN1177) for once-weekly subcutaneous use in adults with overweight or obesity. Our focus was a 12–week multiple ascending dose (MAD), placebo-controlled, double-blind trial in which adults (N=99) received NN1177 (dose-escalated to treatment doses of 200, 600, 1,300, 1,900, 2,800, 4,200, and 6,000 µg) or placebo. Two other trials also contribute to the findings in this report: a first human dose (FHD) / single ascending dose (SAD), placebo-controlled, double-blind trial in which adults (N=49) received NN1177 (treatment doses of 10, 40, 120, 350, 700 and 1,100 μg) or placebo, and a drug–drug interaction (DDI), open-label, single-sequence trial in which adults (N=45) received a 4,200 µg dose of NN1177. Pharmacokinetic, safety and tolerability, and pharmacodynamic endpoints were assessed. For the MAD and FHD/SAD trials, baseline characteristics were generally balanced across groups. The half-life of NN1177 was estimated at between 77.3 and 111 hours. NN1177 appeared tolerable across trials; however, a number of safety concerns were observed, including an increase in heart rate (range 5–22 beats per minute) and decrease in reticulocyte count, which were both dose dependent, and increased markers of inflammation (fibrinogen and C-reactive protein), hepatic disturbances (increased aspartate aminotransferase and alanine aminotransferase), impaired glucose tolerance (dose groups 2,800–6,000 ug) and reduced blood levels of some amino acids. Clinically relevant weight loss was achieved (up to 12.6% at week 12; 4,200 ug in the MAD trial), but this was not accompanied by cardiometabolic improvements. In conclusion, although treatment with NN1177 was associated with dose-dependent and clinically relevant weight loss, unacceptable safety concerns precluded further clinical development.

show abstract

Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Glucagon/GLP-1 receptor co-agonist NNC9204-1177 reduced body weight in adults with overweight or obesity but was associated with safety issues

Friedrichsen

Nygård

Endahl

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…GLP-1 receptor agonists (GLP-1 RAs) are widely used for the treatment of type 2 diabetes (T2D). The benefits of GLP-1 RAs on body weight and the complications associated with obesity are well documented and two members of the drug class, liraglutide and semaglutide, are approved for weight management (as an adjunct to diet and exercise) in individuals with overweight or obesity [ [11] , [12] , [13] , [14] , [15] ]. Furthermore, the drug class has a well-established cardiovascular safety profile, and dulaglutide, liraglutide and once weekly subcutaneous (s.c.) semaglutide are indicated to reduce cardiovascular risk in people with T2D [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

Results from three phase 1 trials of NNC9204-1177, a glucagon/GLP-1 receptor co-agonist: Effects on weight loss and safety in adults with overweight or obesity

Friedrichsen,

Endahl,

Kreiner

et al. 2023

Molecular Metabolism

View full text Add to dashboard Cite

Knowledge and prescribing behaviour of Flemish general practitioners regarding novel glucose-lowering medications: Online cross-sectional survey

Lecomte,

de Beeck,

Mamouris

et al. 2024

Primary Care Diabetes

View full text Add to dashboard Cite

Efficacy of Glucagon-Like Peptide-1 Receptor Agonists in the Weight Loss Among Obese Individuals: A Systematic Review

Cited by 4 publications

References 33 publications

Glucagon/GLP-1 receptor co-agonist NNC9204-1177 reduced body weight in adults with overweight or obesity but was associated with safety issues

Glucagon/GLP-1 receptor co-agonist NNC9204-1177 reduced body weight in adults with overweight or obesity but was associated with safety issues

Results from three phase 1 trials of NNC9204-1177, a glucagon/GLP-1 receptor co-agonist: Effects on weight loss and safety in adults with overweight or obesity

Knowledge and prescribing behaviour of Flemish general practitioners regarding novel glucose-lowering medications: Online cross-sectional survey

Contact Info

Product

Resources

About