The edition · Diabetes & Endocrinology
Survodutide in type 2 diabetes with obesity: 4 to 6 points more weight lost than placebo at 76 weeks
A phase 3 glucagon/GLP-1 dual agonist trial, an FDA sterility recall of compounded incretins, HbA1c and death in cystic fibrosis-related diabetes, a negative immunotherapy trial in new type 1 diabetes, and what the pooled data say about SGLT2 inhibitors in early pregnancy.
The edition in brief
SYNCHRONIZE-2 (NEJM, 1 October) randomised 752 adults with type 2 diabetes and BMI 27 or more to weekly survodutide 3.6 mg, 6.0 mg or placebo. At 76 weeks weight fell 8.2% and 9.8% versus 3.9% with placebo; HbA1c fell about 0.8–0.9 points from 7.4%. Gastrointestinal effects affected about three in four on drug. Survodutide is investigational and not approved anywhere. The FDA lists Class II recalls of compounded tirzepatide and semaglutide products, including vitamin B12 combinations, for lack of assurance of sterility. A UK registry study of 4,477 people with cystic fibrosis-related diabetes found mortality rose stepwise with HbA1c, reaching a rate ratio of 1.93 above 69 mmol/mol. DIABIL-2, a phase 2b trial of low-dose interleukin-2 in 141 people with newly diagnosed type 1 diabetes, expanded regulatory T cells but did not preserve C-peptide. A meta-analysis of three cohorts (669 exposed pregnancies) found no overall rise in major malformations after early SGLT2 inhibitor exposure versus insulin (RR 0.94, 0.68–1.29), but the evidence is low certainty and one cohort raised a cardiac signal for weeks 4–10.
Survodutide in type 2 diabetes with obesity: 8–10% weight loss at 76 weeks
A useful benchmark for dual agonists in diabetes with obesity, but survodutide is not available and outcome data do not exist yet.
FDA Class II recalls: compounded tirzepatide and semaglutide, sterility not assured
Ask every patient on an incretin injection where it is sourced; compounded and unlicensed supplies carry sterility and dosing risks.
Cystic fibrosis-related diabetes: mortality rose stepwise with HbA1c
Consider tighter glucose attention in cystic fibrosis-related diabetes, since higher HbA1c tracked with higher mortality across the range.
Low-dose interleukin-2 did not preserve beta-cell function in new type 1 diabetes
No change to care: low-dose interleukin-2 did not slow beta-cell loss after diagnosis of type 1 diabetes.
Sick-day rules for SGLT2 inhibitors are worth repeating, not just giving once
Restate SGLT2 sick-day rules at every review, and check ketones in any unwell patient taking one.
SGLT2 inhibitors in early pregnancy: no overall malformation rise, but low-certainty evidence
Counsel an exposed woman calmly, switch at once, and consider fetal cardiac scanning; do not continue the drug in pregnancy.
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