SURPASS-6
SURPASS-6 addressed one of the most clinically common and difficult decision points in T2D management: what to do when a patient on basal insulin still has inadequate blood sugar control. The standard next step is to add prandial (mealtime) insulin lispro three times daily — a significant escalation in injection burden and hypoglycaemia risk. SURPASS-6 tested whether adding once-weekly tirzepatide instead could achieve better or equal glycaemic control with a lower burden.
Ontology SURPASS-6 [part-of] SURPASS Clinical Trial Programme SURPASS-6 [studied_in] Tirzepatide SURPASS-6 [measured_by] HbA1c Reduction SURPASS-6 [measured_by] Insulin-Use Reduction SURPASS-6 [compared_against] Insulin Lispro SURPASS-6 [relates] Hypoglycaemia Risk SURPASS-6 [relates] Type 2 Diabetes
Key Results
- HbA1c change from baseline: −2.1% (tirzepatide pooled) vs −1.1% (insulin lispro); p<0.001 — both non-inferiority and superiority achieved
- Mean HbA1c at week 52: 6.7% (tirzepatide) vs 7.7% (lispro); difference −0.98% (95% CI −1.17 to −0.79)
- HbA1c <7.0%: 68% (tirzepatide) vs 36% (lispro); OR 4.2 (95% CI 3.2–5.5)
- Body weight: −9.0 kg (tirzepatide) vs +3.2 kg (lispro); difference −12.2 kg (95% CI −13.4 to −10.9)
- Hypoglycaemia events (<54 mg/dL or severe): 0.4 events/patient-year (tirzepatide) vs 4.4 (lispro) — 11× lower
- Trial completion: 91.3% (1304/1428)
- GI events (tirzepatide): Nausea 14–26%, diarrhoea 11–15%, vomiting 5–13%
- Discontinuation: Low; specific figures not in abstract
Key clinical implication: In patients on basal insulin requiring intensification, tirzepatide added to basal insulin achieved better HbA1c (mean 6.7%), greater weight loss (−9 kg), and dramatically lower hypoglycaemia (11× fewer events) compared to adding prandial insulin three times daily.
Limitations
- Trial design: Open-label (cannot blind injection differences between tirzepatide once weekly vs lispro TID)
- Population: Already on basal insulin; baseline HbA1c 8.8% — relatively advanced disease; mean age 58.8 years; long-term durability not assessed
- Duration: 52 weeks — no data beyond 1 year for this basal-insulin population
- Sponsorship: Eli Lilly-funded; multiple author COI
Connections
- Tirzepatide — studied_in, [2023], source: PMID 37786396
- HbA1c Reduction — measured_by, [2023], source: PMID 37786396
- Insulin-Use Reduction — measured_by, [2023], source: PMID 37786396
- Insulin Lispro — comparator_in, [2023]
- Insulin Glargine — background_therapy, [2023]
- Hypoglycaemia Risk — measured_by, [2023]
- SURPASS Clinical Trial Programme — part-of