SURPASS-5
SURPASS-5 (JAMA 2022, Dahl D et al., PMID 35133415) evaluated the addition of once-weekly tirzepatide to titrated insulin glargine in 475 adults with T2D inadequately controlled on basal insulin alone or with metformin. This 40-week phase 3 trial at 45 centres across 8 countries addresses a common clinical scenario: a patient whose HbA1c remains above target despite basal insulin — what should be added?
Glycaemic outcomes: Tirzepatide added to basal insulin produced substantially better HbA1c reductions vs placebo added to the same background: −2.40% (10mg) and −2.34% (15mg) vs −0.86% (placebo), with estimated treatment differences of −1.53% and −1.47% respectively (both P<0.001). HbA1c <7.0% was achieved in 85–90% of tirzepatide-treated patients versus only 34% of placebo patients — a strikingly favourable result in a population that had already failed basal insulin alone.
Weight: Tirzepatide produced weight loss of −6.2 to −10.9 kg from baseline versus a weight gain of +1.7 kg with placebo. In a population where further insulin dose increases typically drive weight gain, this metabolic advantage is clinically important.
Hypoglycaemia: Hypoglycaemia rates were similar between tirzepatide (14–19%) and placebo (13%) because the trial protocol required a 20% reduction in insulin glargine dose for patients with HbA1c ≤8.0% at randomisation, and all patients continued treat-to-target glargine titration. This is important for clinical practice: proactively reducing basal insulin when starting tirzepatide prevents hypoglycaemia and is supported by this protocol.
Vault context: SURPASS-5 is the reference trial for “adding tirzepatide to existing basal insulin.” Combined with SURPASS-6 (adding tirzepatide vs adding prandial insulin), the clinical case is clear: for a patient on basal insulin with inadequate control, tirzepatide is strongly preferred over either increasing basal insulin dose or adding prandial insulin. The 20% glargine dose-reduction rule at initiation should be standard practice guidance.
Ontology SURPASS-5 [evidence_for] Tirzepatide SURPASS-5 [relates] Insulin-Use Reduction SURPASS-5 [relates] Advanced T2D High-Dose Insulin SURPASS-5 [relates] SURPASS Clinical Trial Programme
Numbers
| Arm | HbA1c Δ | Weight Δ | HbA1c <7.0% | Hypoglycaemia |
|---|---|---|---|---|
| Tirzepatide 5mg | ~−1.87% | −6.2 kg | 85% | 14% |
| Tirzepatide 10mg | −2.40% | ~−9 kg | 90% | 19% |
| Tirzepatide 15mg | −2.34% | −10.9 kg | 90% | 19% |
| Placebo | −0.86% | +1.7 kg | 34% | 13% |
Baseline HbA1c: ~8.5% | Background: insulin glargine + optional metformin | Duration: 40 weeks
Practical Interpretation
- Who this applies to: T2D patients on basal insulin with HbA1c above target — add tirzepatide rather than increasing insulin
- Key protocol point: Reduce glargine by 20% at tirzepatide initiation if HbA1c ≤8.0%; continue treat-to-target titration
- Vs SURPASS-6: SURPASS-5 is the add-on to basal placebo-controlled proof; SURPASS-6 is the active comparator (add tirzepatide vs add prandial insulin)
Connections
- Tirzepatide — evidence_for (add-on to basal insulin)
- SURPASS-6 — relates (companion trial: add tirzepatide vs add prandial)
- Insulin-Use Reduction — evidence_from
- Advanced T2D High-Dose Insulin — evidence_from (basal insulin context)
- Hypoglycaemia Risk — evidence_from (low when glargine proactively reduced)