SGLT2 inhibitors lift haemoglobin by about 0.6 g/dL — expect it, and read past it

The edition in brief

A JAMA meta-analysis of 85 double-blind randomised trials (70,543 participants) found SGLT2 inhibitors raised haemoglobin by 0.60 g/dL and haematocrit by 2.36 percentage points more than control, with a small rise in erythropoietin and a small fall in transferrin saturation. The authors call the clinical significance unclear; in practice it means a modest rise is an expected drug effect, not a reason to investigate polycythaemia, and a falling haemoglobin on treatment still needs explaining. ACHIEVE-4, an open-label phase 3 trial in 2,749 adults with type 2 diabetes and established cardiovascular or kidney disease, found oral orforglipron non-inferior to insulin glargine for four-point MACE (HR 0.84, 95% CI 0.59–1.20), with less hypoglycaemia (6.8% vs 19.2%) and far more gastrointestinal effects (62.1% vs 14.2%). A post-hoc landmark analysis of J-DOIT3 found no clear lower HbA1c threshold for myocardial infarction or death when severe hypoglycaemia was rare. Thirty-four years of Da Qing follow-up linked at least 5% weight loss after impaired glucose tolerance with lower cardiovascular death (HR 0.56). The FDA has posted Class II recalls of compounded semaglutide and tirzepatide syringes from a US compounder for lack of sterility assurance.