The edition · Diabetes & Endocrinology
Semaglutide response cannot be predicted at baseline — dose and time decide it
In 7,594 SELECT participants, baseline characteristics explained under 10% of peak weight loss. Also: orforglipron dose comparison, PMOS as a pregnancy risk marker, CGM trajectories in type 1, and weekly ketone checks.
The edition in brief
A prespecified SELECT analysis found that clinically available baseline characteristics explained less than 10% of the variation in peak weight loss on semaglutide; median peak loss was 12.5%, reached after a median of 19 months, and those who reached 2.4 mg lost far more than those stuck at low doses. Women lost more than men. A meta-analysis of six trials (3,459 adults) found orforglipron 36 mg gave greater weight, HbA1c, waist, triglyceride and systolic pressure reductions than 12 mg, with comparable adverse events but small ALT and AST rises. In a nested cohort of 3,645 pregnant women at risk of hyperglycaemia, polyendocrine metabolic ovarian syndrome (PMOS, formerly PCOS) was associated with early gestational diabetes (aOR 1.37) and worse neonatal outcomes. A three-year CGM study in 1,028 adults with type 1 diabetes found older adults and those with CKD improved time in range without more hypoglycaemia, while severe beta-cell failure limited gains. A modelling study from the EASE trials found weekly well-day capillary ketone testing predicted next-month DKA risk as well as twice-weekly testing.
Baseline features barely predict who loses most weight on semaglutide
Titrate semaglutide to the full dose and judge response over 18–24 months, because nothing at baseline tells you who will respond.
Orforglipron 36 mg outperforms 12 mg on weight and glycaemia with similar tolerability
Where orforglipron is available and tolerated, the 36 mg maintenance dose gives more metabolic benefit than 12 mg without a clear tolerability cost.
PMOS is linked to early gestational diabetes and poorer neonatal outcomes
Treat PMOS as an independent reason to screen for gestational diabetes early in pregnancy, whatever the woman's BMI.
Older adults and those with CKD improve time in range on CGM over three years
Use each person's CGM trajectory to set targets, and expect less improvement in those with severe beta-cell failure.
Ask about PMOS in every woman with diabetes risk who may become pregnant
Record PMOS on the problem list of every woman with metabolic risk, because it changes pregnancy screening.
Weekly well-day ketone checks predict DKA risk as well as twice-weekly checks
Ask people with type 1 diabetes at DKA risk to check capillary ketones once a week on a well day, in addition to sick-day testing.
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