The edition · Diabetes & Endocrinology
Metformin does not prevent gestational diabetes
Ten trials, 2,297 pregnancies, no reduction in gestational diabetes on the two commonest sets of criteria. Plus 25-year prevention data, an oral GLP-1 safety readout from Japan, and a quiet regulatory day.
The edition in brief
The strongest finding today is negative. A patient-level meta-analysis of ten double-blind trials, covering 2,297 pregnancies without diabetes, found that metformin did not reduce gestational diabetes on World Health Organization 1999 or NICE 2015 criteria. It did lengthen gestation slightly and lower the odds of preterm birth, but it should not be started in pregnancy for the purpose of preventing gestational diabetes. Long-term follow-up of the Diabetes Prevention Program adds weight to structured lifestyle programmes. Among 1,173 adults with prediabetes followed to a median age of 74, the lifestyle arm had a lower risk of multimorbidity than placebo, while metformin did not differ from placebo. From Japan, a 52-week phase 3 safety study of once-daily oral orforglipron in 401 adults with type 2 diabetes showed an acceptable safety profile, with discontinuations for adverse events rising from 5 percent at 3 mg to 14 percent at 36 mg, driven by gastrointestinal symptoms and no severe hypoglycaemia. That matters for Indian practice, where an oral GLP-1 receptor agonist would remove the injection, the device and the cold chain. Follow-up of the BANDIT trial shows that baricitinib's protection of beta-cell function in new-onset type 1 diabetes is lost within a year of stopping the drug. Mazdutide, a glucagon and GLP-1 dual agonist, gave 18.1 percent weight loss at 16 mg in a US phase 2 trial, at the cost of 20 percent discontinuation at that dose. The clinic pearl: read the ambulatory glucose profile by day of the week before changing an insulin dose. No new diabetes-specific regulatory action today.
Metformin in high-risk pregnancy does not prevent gestational diabetes
Metformin started in a high-risk pregnancy without diabetes does not prevent gestational diabetes, so stop using it for that purpose.
Twenty-five years on, lifestyle rather than metformin was linked to less multimorbidity
Refer patients with prediabetes to a structured lifestyle programme - it, not metformin, was linked to less multimorbidity 25 years later.
Oral orforglipron: 52-week safety in Japanese adults with type 2 diabetes
Oral orforglipron was tolerated over 52 weeks in Japanese adults with type 2 diabetes, with discontinuation rising from 5 per cent at 3 mg to 14 per cent at 36 mg.
Baricitinib's benefit in new-onset type 1 diabetes fades within a year of stopping
Beta-cell preservation from baricitinib is lost within a year of stopping, so counsel patients that these are continuous treatments rather than a cure.
Mazdutide cut weight by 18 per cent at the highest dose in a US phase 2 trial
Mazdutide, a glucagon and GLP-1 dual agonist, gave 18 per cent weight loss at 16 mg in phase 2, but one in five stopped that dose - promising, not prescribable.
Read the glucose profile by day of the week before you change a dose
Before adjusting insulin from an average time-in-range figure, ask what weekends and evenings look like - that is where control slips.
A quiet regulatory day for diabetes
Nothing new in diabetes regulation today; the most recent relevant decision is the US approval of the first oral PCSK9 inhibitor.
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