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HbA1c reduction with tirzepatide in people with type 2 diabetes: The contribution of weight loss assessed by a mediation analysis
How weight loss may contribute to blood sugar improvement with tirzepatide in type 2 diabetes
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Abstract
The difference in mean HbA1c change from baseline at 40 weeks between tirzepatide and placebo ranged from -20.0 to -14.6 mmol/mol.
- Mediation analysis showed 12%-27% of the HbA1c reduction difference between tirzepatide and placebo was linked to weight loss when tirzepatide was used alone.
- When tirzepatide was used alongside insulin with or without metformin, 25%-45% of the HbA1c difference was associated with weight loss.
- Comparing tirzepatide with semaglutide, weight loss accounted for 54%-71% of the observed difference in HbA1c changes.
- Tirzepatide's effects on HbA1c reduction were associated with both weight loss-dependent and weight loss-independent mechanisms.
- The contribution of weight loss to glycaemic efficacy varied depending on the comparator, being more significant against semaglutide than placebo.
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Key numbers
-20.0 to -14.6 mmol/mol
HbA1c Reduction vs. Placebo
Difference in mean HbA1c change at Week 40.
12%–27%
Weight Loss Mediation Percentage
Mediation analysis in placebo-controlled trials.
54%–71%
Weight Loss Mediation Percentage vs. Semaglutide
Mediation analysis comparing tirzepatide to semaglutide 1 mg.