Orforglipron in type 2 diabetes mellitus and obesity: an overview

📖 Top 20% JournalNov 23, 2025Expert review of clinical pharmacology

Orforglipron’s effects in type 2 diabetes and obesity

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Abstract

Orforglipron has led to reductions in glycated hemoglobin (HbA) by up to 2.10% and weight by up to 10.1 kg in individuals with type 2 diabetes mellitus.

In studies involving individuals with type 2 diabetes mellitus, orforglipron resulted in a significant decrease in waist circumference by up to 8.7 cm.
For overweight or obese individuals, weight loss of up to 13.0 kg has been reported with orforglipron treatment.
Meta-analyses indicated that orforglipron was the most effective GLP-1 receptor agonist for weight loss.
There were significant decreases in systolic blood pressure in individuals with and without type 2 diabetes mellitus.
Mild-to-moderate vomiting and nausea were noted as adverse effects, especially at high doses and after rapid-dose escalation.

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INTRODUCTION: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are widely used in the management of type 2 diabetes mellitus (T2DM) and obesity.

AREAS COVERED: An electronic search was conducted in Scopus, PubMed/MEDLINE, and Google Scholar databases. Orforglipron is a novel oral non-peptide GLP-1RA. In T2DM individuals, it has led to reductions in glycated hemoglobin (HbA) by up to 2.10%, in weight by up to 10.1 kg and in waist circumference by up to 8.7 cm. In studies on overweight or obesity, a weight loss up to 13.0 kg has been reported. In meta-analyses, orforglipron was the most efficient GLP-1RA in terms of weight loss. Significant decreases in systolic blood pressure have also been found in individuals with and without T2DM. Untoward effects include mild-to-moderate vomiting and nausea, particularly in those receiving high doses and after rapid-dose escalation. 1c

EXPERT OPINION: Orforglipron is a promising treatment option for T2DM and overweight or obesity, in terms of glucose control and weight loss. The increased frequency of adverse events, particularly in those receiving high doses and after rapid-dose escalation, requires caution before widespread use.

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