Dulaglutide

Primary endpoint occurred in 12.2% of tirzepatide group vs 13.1% of dulaglutide group (HR 0.92; 95.3% CI 0.83–1.01; P=0.003 for noninferiority).; Superiority of tirzepatide was not established (P=0.09).; Adverse events were similar between groups, though more gastrointestinal events occurred with tirzepatide.

Switching to tirzepatide led to a significantly greater HbA1c reduction than escalating dulaglutide (estimated treatment difference -0.77%).; Weight loss was significantly greater with tirzepatide (-10.5 kg) versus dulaglutide (-3.6 kg).; Serious adverse event rates were similar between groups (7.2% tirzepatide vs 7.0% dulaglutide).; Most common adverse events were nausea and diarrhea in both groups.

GLP-1RAs (liraglutide and dulaglutide) reduce binge eating frequency and comorbidities.; GLP-1RAs have a favorable psychiatric side effect profile compared to current options.; Large-scale, blinded placebo-controlled trials are lacking.; Rigorous clinical trials are needed to establish efficacy, dosing, safety, and comparative effectiveness.

Participants receiving dulaglutide drank 29% less alcohol at week 12 than those on placebo (relative effect = 0.71, 95% CI 0.52-0.97, P = 0.04).; Changes in alcohol consumption were not correlated with smoking status at week 12.; The study included 151 participants who reported drinking at baseline and completed 12 weeks of treatment (76 dulaglutide, 75 placebo).; Results support the potential of GLP-1 agonists for treating substance use disorders.

Orforglipron at doses ≥12 mg produced statistically superior HbA1c reductions versus placebo (treatment difference -0.8% to -1.7%).; Maximum body weight loss with orforglipron was -10.1 kg (placebo-adjusted -7.9 kg), compared to -2.2 kg with placebo and -3.9 kg with dulaglutide.; Treatment-emergent adverse events occurred in 61.8% to 88.9% of orforglipron groups, mostly mild-to-moderate gastrointestinal events.; Clinically significant hypoglycemia occurred in 3 orforglipron participants and 1 dulaglutide participant; no severe hypoglycemia or treatment-related deaths were reported.

Tirzepatide 5, 10, and 15 mg reduced HbA1c by -2.4%, -2.6%, and -2.8% respectively, versus -1.3% for dulaglutide (all p<0.0001).; Tirzepatide led to dose-dependent body weight reductions of -5.8 kg to -10.7 kg, compared with -0.5 kg for dulaglutide.; The most common adverse events were nausea, constipation, and nasopharyngitis, with gastrointestinal events occurring in 4% of patients.

Future CVOTs may face ethical challenges with placebo controls due to proven cardiovascular benefits of GLP-1 RAs and SGLT-2i.; The SURPASS CVOT is the first active-controlled CVOT designed to demonstrate cardiovascular efficacy of tirzepatide versus dulaglutide.; Non-inferiority to dulaglutide is defined as preserving at least 50% of its cardiovascular benefit, with superiority assessed via imputed placebo.; The imputed placebo method uses a hierarchical Bayesian meta-analysis of prior placebo-controlled GLP-1 RA trials to estimate dulaglutide's efficacy margin.

What is Dulaglutide?

**Mechanism of Action** Dulaglutide is a long-acting glucagon-like peptide-1 (GLP-1) receptor agonist engineered by fusing two GLP-1 analog molecules to a modified human immunoglobulin G4 (IgG4) Fc fragment. This structure extends its half-life to approximately 5 days, enabling once-weekly subcutaneous administration.

How does Dulaglutide work?

Once-weekly GLP-1 receptor agonist fused to an IgG4 Fc fragment for extended half-life.

What is the research status of Dulaglutide?

Dulaglutide is currently classified as approved, with 1,252 research references on record. This is for research purposes only and is not medical advice.

What is the half-life of Dulaglutide?

The reported half-life of Dulaglutide is ~5 days.