Haemoglobin A1c (HbA1c) reduction with tirzepatide in people with type 2 diabetes: The contribution of weight loss assessed by a mediation analysis
Authors' conclusion
The tirzepatide-induced HbA1c reductions from baseline, compared with placebo or semaglutide, were mediated through both WL-D and WL-IND effects. Estimated contributions of WL to the difference in glycaemic efficacy varied and were highest when tirzepatide was compared with semaglutide and less pronounced when compared with placebo. These results help to understand that other factors beyond weight reduction contribute to HbA1c reduction with tirzepatide.
Study context
- Population
- People with T2D in the SURPASS 1, 2 and 5 trials
- Participants
- 2,831 people3 RCTs
- Comparison
- Tirzepatide vs placebo or semaglutide
- Primary endpoint
- WL-dependent and WL-independent effects on comparator-adjusted HbA1c reduction
- Follow-up
- Week 40
Methodological detailsSURPASS 1, 2 and 5, randomized, parallel, 4-arm
- SURPASS 1, 2 and 5
- Randomized
- Parallel
- 4-arm
Primary result
As reported in the abstract
Tirzepatide vs placebo, monotherapy (S1): share of HbA1c difference mediated through weight loss (WL)
12%-27%
Tirzepatide vs placebo, on insulin ± metformin (S5): share of HbA1c difference mediated through WL
25%-45%
Tirzepatide vs semaglutide: share of HbA1c difference WL dependent (WL-D)
54%-71%
Further findings
| Outcome | Difference in mean HbA1c change (range) (mmol/mol) |
|---|---|
| Total effect: difference in mean HbA1c change from baseline · 40 weeksTirzepatide vs Placebo | −20.0 to −14.6 |
| Total effect: difference in mean HbA1c change from baseline · 40 weeksTirzepatide vs Semaglutide | −5.1 to −1.9 |
Original publication
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