Oral GLP-1 safety data land, and every gestational diabetes subtype turns out to matter

The edition in brief

Today's edition is led by ACHIEVE-J, a 52-week open-label phase 3 safety trial of once-daily oral orforglipron in 401 Japanese adults with type 2 diabetes. The safety picture was familiar rather than novel: 85% had at least one treatment-emergent adverse event, most mild or moderate, and discontinuation for adverse events tracked the dose, from 5% at 3 mg to 14% at 36 mg, driven by gastrointestinal symptoms. There was no severe hypoglycaemia. A prospective follow-up of 4,693 women 10 to 14 years after delivery found that every physiological subtype of gestational diabetes except the small unclassified group carried a higher risk of prediabetes or diabetes, with adjusted risk ratios of 2.14 to 2.88. Subtyping did not identify anyone who could be safely discharged from follow-up. A study of 1,129 people referred for MODY genetic testing found about one in five actually had type 1 diabetes. A type 1 genetic risk score used before the panel discriminated poorly overall but well in children under 10, where more than half of tests could have been avoided. Today's pearl is to halve the sulphonylurea and trim basal insulin on the same day a GLP-1 receptor agonist is started, not at the next visit. In research, a US phase 2 trial of mazdutide, a glucagon and GLP-1 dual agonist, reached 15.6% to 18.1% weight loss at 32 weeks with 20% stopping at 16 mg; and follow-up of the BANDIT trial showed baricitinib's beta-cell preservation faded within a year of stopping. The regulatory sweep found nothing new.