Two studies went into this pool. They disagree with each other by 98%.
What I² of 98 means
Heterogeneity measures how much the variation between studies exceeds what chance would produce. At 98%, almost none of the difference between these two trials is random. [1]
Averaging them anyway gives −0.37% on HbA1c with an interval from −0.95 to 0.21 — a wide null. The honest reading is not that the combination fails to control glucose. It is that these two trials measured something different enough that one number cannot stand for both.
One compared against weekly insulin icodec alone and the other against full basal-bolus therapy. Those are different comparators, which is reason enough for the answers to diverge, and it is the same difficulty as comparing by inference.
What did move
Weight fell 6.10 kg against insulin-based intensification, interval 7.21 to 5.00. That is a large and consistent difference, and it is what you would expect from adding semaglutide to a regimen whose alternative is more insulin.
Systolic pressure fell 2.45 mmHg. Total cholesterol, LDL, triglycerides and VLDL all fell, with ratios between 0.94 and 0.97 — improvements of a size that the widest observational view also reports across cardiometabolic measures.
The appendix nobody should quote
The paper includes an exploratory model estimating what these marker changes might do to cardiovascular risk. Its authors describe it as hypothetical and intended as an illustration only, and they put it in a supplementary appendix.
We mention it so that anyone who meets a number from it elsewhere knows what they are looking at. A risk figure derived from surrogate movements is arithmetic about assumptions, not evidence about people, the way a number needed to treat built from counted events is.
What it would mean if it worked
One injection a week instead of several a day, with less weight and a lower chance of hypoglycemia than insulin intensification. For somebody on basal-bolus therapy that is a genuine improvement in how a life is lived.
It is also the same trade as swapping mealtime insulin for a GLP-1 — fewer injections and less weight, bought at a price nobody in either analysis calculated.