Pooling three randomized trials (1,506 adults with type 2 diabetes), weekly CagriSema 2.4/2.4 mg cut body weight 2.07 percentage points more than the 1.0/1.0 mg dose (95% CI -2.91 to -1.24). That gap stayed entirely below the authors' prespecified 3-point minimal important difference. More people reached 10% weight loss (64.9% vs 55.1%) and 15% loss (41.9% vs 30.9%). HbA1c did not differ significantly (-0.16 points; CI -0.43 to 0.10). Gastrointestinal disorders rose (64.8% vs 53.2%; RR 1.22), while serious events and discontinuations did not.
The real value here is a head-to-head dose question the individual trials never answered, and the answer is sobering for a more-is-better assumption. The higher dose delivers a statistically real but clinically borderline weight advantage, no demonstrated glycemic edge, and a roughly 12-point absolute rise in GI side effects. For adults with type 2 diabetes weighing obesity-related risk against tolerability, that supports individualized dosing, which is worth raising with a prescriber. Caveats matter: the comparison is indirect, built from arm-level estimates across trials rather than randomization between doses, and only three trials contributed. Outcomes are surrogate markers, so nothing here speaks to cardiovascular events or mortality. This is a preprint awaiting peer review, and conclusions could shift. Editorially, it is incremental and confirmatory: it sharpens dose selection rather than changing what the drug class can do.