Originally published by 2 Minute Medicine® (view original article). Reused on AccessMedicine with permission.

1. HbA1c and bodyweight reduction were greater in the retatrutide group compared to dulaglutide and placebo.

2. The effect of retatrutide on body weight was dose-dependent at 36 weeks.

Evidence Rating Level: 1 (Excellent)

Study Rundown:

Effective management of type 2 diabetes involves glycemic control and bodyweight management. Glucagon-like peptide 1 (GLP-1) receptor agonists are often used as first-line therapy for the management of type 2 diabetes. Retatrutide – a single peptide with GLP-1, glucose-dependent insulinotropic peptide (GIP), and glucagon agonist activity – may be used for glucose and bodyweight reduction, although little is known. This randomized controlled trial aimed to assess the safety and efficacy of retatrutide versus dulaglutide and placebo in individuals with type 2 diabetes. The primary outcome of this study was mean change in HbA1c at 24 weeks while a key secondary outcome included mean change in body weight at 36 weeks. According to study results, retatrutide resulted in significant reductions in glycemic control and body weight compared to dulaglutide and placebo. The majority of side effects were mild-to-moderate in nature with no reported deaths. This study was strengthened by a large sample size with longitudinal follow-up of patients.

In-depth [randomized-controlled trial]:

Between May 13, 2021, and June 13, 2022, 534 patients were screened for eligibility across 42 centers in the USA. Included were patients ≥ 18 years old with type 2 diabetes, HbA1c 7·0–10·5%, and BMI 25–50 kg/m2. Altogether, 281 patients (45 in placebo, 46 in 1.5 mg dulaglutide group, 47 in retatrutide 0.5 mg group, 23 in 4 mg escalation group, 24 in 4 mg group, 26 in 8 mg escalation group, 24 in 8 mg fast escalation group, and 46 in 12 mg escalation group) were included in the final analysis. The primary outcome of HbA1c reduction at 24 weeks was greatest in the retatrutide 12 mg escalation group (-2.02%, standard error [SE] 0.11, -22.07 mmol/mol) and significantly greater compared to 1.5 mg dulaglutide group (-1.41%, SE 0.12, -15.40 mmol/mol; p=0.0019) and placebo (-0.01%, SE 0.21, -0.12 mmol/mol; p<0.0001). Retatrutide also showed dose-dependent reductions in body weight at 36 weeks (3.19% for 0.5 mg group vs. 10.37% for 4 mg group vs. 16.81% for 8 mg slow escalation group). Overall, findings from this study suggest that retatrutide holds promise in achieving meaningful improvements in glycemic control and body weight reduction for patients with type 2 diabetes.

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