The edition · Diabetes & Endocrinology
A once-weekly insulin-GLP-1 combination beats daily glargine, and the lipid goalposts move
COMBINE 4 shows once-weekly icodec plus semaglutide outperforming daily glargine on HbA1c, weight and hypoglycaemia. Meanwhile the 2026 dyslipidaemia guideline pulls millions of lower-risk adults into statin therapy, and two safety reviews sharpen what to watch on incretins and SGLT2 inhibitors.
The edition in brief
Today's edition leads with COMBINE 4, a 40-week phase 3b trial in 485 insulin-naive adults with type 2 diabetes and HbA1c of 8% or above. Once-weekly IcoSema (insulin icodec plus semaglutide) lowered HbA1c by 0.88 percentage points more than daily glargine U100, produced a 4.61 kg weight difference in its favour, and roughly halved clinically significant or severe hypoglycaemia. It is the first time a once-weekly injection has beaten daily basal insulin on all three fronts at once. A meta-analysis of 32 trials and 47,332 people separates tirzepatide from semaglutide on blood pressure: tirzepatide cuts hypertension events but more than doubles hypotension events, and the effect grows with dose. Semaglutide looks neutral. The practical consequence is to review antihypertensives and check standing blood pressure as you titrate. The 2026 AHA/ACC dyslipidaemia guideline expands US primary-prevention statin eligibility to an estimated 87.5 million adults, 21.5 million of them newly eligible and mostly younger and at lower risk. Long-term Diabetes Prevention Program follow-up finds lifestyle intervention, but not metformin, lowered multimorbidity over 25 years. Two evidence reviews add caution. A Cochrane network meta-analysis of 18 studies confirms large weight and HbA1c gains after gastric bypass but rates the evidence on complete diabetes remission, serious harms and mortality as very uncertain. A review of SGLT2 inhibitors quantifies the rise in haemoglobin and haematocrit and flags a minority who develop clinically significant erythrocytosis. The pearl covers non-HDL cholesterol as the working lipid target in a diabetes clinic.
Once-weekly icodec plus semaglutide beats daily glargine on glucose, weight and hypoglycaemia
Once-weekly insulin icodec plus semaglutide gave a 0.88 percentage point bigger HbA1c fall, 4.61 kg less weight and about half the significant hypoglycaemia of daily glargine, so plan for it as the future first insulin in orals-failing type 2 diabetes.
Tirzepatide lowers blood pressure enough to cause hypotension - semaglutide does not
Tirzepatide cuts hypertension events but roughly doubles hypotension events in a dose-dependent way, so check standing blood pressure at each titration step and plan to reduce antihypertensives, particularly diuretics.
No new drug approvals or safety communications today - but the 2026 lipid guideline redraws statin eligibility
Nothing new from regulators today; the 2026 dyslipidaemia guideline widens statin eligibility to 56.6% of US adults aged 30 to 79, mostly younger and lower-risk people, while your patients with diabetes were already eligible and stay so.
Twenty-five years on, lifestyle intervention cut multimorbidity in prediabetes - metformin did not
In 25-year follow-up of the Diabetes Prevention Program, structured lifestyle intervention was associated with a fifth lower risk of developing multiple chronic conditions while metformin was not, so refer to a real programme rather than relying on the drug.
SGLT2 inhibitors reliably raise haemoglobin - and in a minority the rise matters
Expect haemoglobin to rise about 0.5 g/dL and haematocrit about 2 percentage points on an SGLT2 inhibitor; check a full blood count at baseline and around 6 months, and only investigate when the rise goes well beyond that.
Cochrane on bariatric surgery: large weight and HbA1c gains, but the remission evidence is weaker than the reputation
Gastric bypass produces about 17% more long-term weight loss and 1.44 percentage points more HbA1c reduction than non-surgical care, but the evidence on complete diabetes remission, serious harms and mortality is very uncertain - say so when consenting.
Use non-HDL cholesterol as your working target, especially when triglycerides are raised
Calculate non-HDL cholesterol on every lipid report - total minus HDL - and treat to the LDL goal plus 30 mg/dL, because calculated LDL undertreats the high-triglyceride, low-HDL pattern common in Indian patients.
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