- Design
- Systematic review and frequentist network meta-analysis of 30 randomised trials
- Population
- 17,862 adults with type 2 diabetes
- Primary outcome
- Change in HbA1c and body weight versus basal insulin
- Effect
- HbA1c −0.53% to −0.72%; weight up to −3.16 kg versus basal insulin; no significant differences between FRCs
A network meta-analysis pooled 30 randomised trials with 17,862 adults with type 2 diabetes, comparing basal insulin–GLP-1 receptor agonist fixed-ratio combinations (FRCs) with basal insulin as the reference.
Every FRC lowered HbA1c and body weight more than basal insulin alone. The largest HbA1c reductions were HR17031 (−0.72%), insulin degludec/liraglutide (−0.64%) and insulin glargine/lixisenatide (−0.53%). For weight, insulin icodec/semaglutide led (−3.16 kg). FRCs also raised the proportion reaching HbA1c below 7%, often without weight gain or more severe hypoglycaemia.
The rankings are the weak part. No head-to-head difference between FRCs reached significance, and certainty was low to very low for most indirect comparisons. Choose between products on availability, cost and dosing range, not on rank.
For a patient already on basal insulin who is above target, switching to an FRC is a reasonable way to add a GLP-1 receptor agonist in one daily injection. Availability and price of individual combinations in India vary, so check before promising one.
- Consider a fixed-ratio combination when basal insulin alone leaves HbA1c above target
- Expect about 0.5–0.7% extra HbA1c lowering over basal insulin, with weight neutral or lower
- Do not choose between combinations on their ranking — no product was clearly better than another
- Remember the fixed ratio caps the GLP-1 dose as insulin is titrated, so check the dose range fits the patient
- Warn about nausea in the first weeks of titration
Why it matters
Intensifying basal insulin no longer has to mean adding prandial injections and kilograms.
Don't overread it
The product rankings come from indirect comparisons of low certainty; no combination was shown to beat another.
The statistics, in plain English
A mean difference of −0.64% means HbA1c fell about two-thirds of a percentage point more than on basal insulin alone. A network meta-analysis estimates comparisons between drugs never tested against each other by routing through a shared comparator, which is why those indirect rankings carry low certainty.
Read the rest in the app
You have read your two free briefings this month. The app carries all 27 specialties, every morning, free — and this finding is waiting in it.
Scan to keep reading on your phone. No account needed to start.
Tomorrow morning, before your first patient
One edition a day for diabetes & endocrinology, written by the desk, every claim tied to its paper. Six minutes.
Get the app — free