An oral GLP-1 agonist holds its own against glargine on heart safety, with far less hypoglycaemia

The edition in brief

ACHIEVE-4 randomised 2,749 adults with type 2 diabetes and established cardiovascular or kidney disease to oral orforglipron or insulin glargine. Over about two years, major cardiovascular events occurred in 4.2% versus 5.0% (HR 0.84, 95% CI 0.59–1.20), meeting the non-inferiority margin. Severe or clinically significant hypoglycaemia was 6.8% versus 19.2%, but gastrointestinal events were 62% versus 14%. The trial was open-label and designed for safety, not superiority. TRIUMPH-2 tested weekly retatrutide in 1,152 adults with obesity and type 2 diabetes: weight fell 18.8% on 12 mg versus 5.1% on placebo at 80 weeks, with more diarrhoea, nausea, hypotension and dysaesthesia, and treatment stopped for adverse events in up to 12%. From the HAPO follow-up, every main subtype of gestational diabetes was associated with two to three times the risk of prediabetes or diabetes 10–14 years later, so subtype should not decide who gets screened. An Australian registry of 5,202 people with childhood-onset type 1 diabetes found onset before age 7 was associated with lower complication risk over the first 20 years than onset at 13–15 years, which argues for close surveillance of those diagnosed in adolescence. The pearl covers how to start an oral or injectable incretin without derailing a patient on a sulfonylurea or insulin.