Comparative efficacy and tolerability of currently approved incretin mimetics: A systematic analysis of placebo‐controlled clinical trials
Authors' conclusion
The magnitude of efficacy for intended therapeutic actions (HbA1c and body weight reduction) varied widely between incretin mimetic glucose-lowering agents. However, larger therapeutic efficacy was not systematically associated with higher GI AE or drug discontinuation rates, indicating better tolerability of the more effective agents/preparations.
Study context
- Population
- Individuals with T2D in placebo-controlled RCTs; mean age 57 ± 10 years, diabetes duration 8 ± 6 years, body mass index (BMI) 31.9 ± 5.8 kg/m², HbA1c 8.2% ± 0.9%
- Participants
- 16,660 individuals38 RCTs104 study arms
- Comparison
- GLP-1 RAs and tirzepatide (dual GLP-1/GIP agonist), each vs placebo, compared across agents, preparations and doses
- Outcome
- HbA1c change
Methodological detailsplacebo-controlled, phase 3 or 4 RCTs, linear regression analysis, Systematic PubMed search
- Placebo-controlled
- Phase 3 or 4 RCTs
- Linear regression analysis
- Systematic PubMed search
Pooled result
As reported in the abstract
| Group | Value | Dose |
|---|---|---|
| Lixisenatide | −0.63 (unspecified 0.03) % | 20 μg q.d. |
| Tirzepatide | −1.79 (unspecified 0.09) % | 15 mg q.w. |
Value
Lixisenatide−0.63 (unspecified 0.03) %
Tirzepatide−1.79 (unspecified 0.09) %
Dose
Lixisenatide20 μg q.d.
Tirzepatide15 mg q.w.
- Tirzepatide vs Lixisenatide: P < 0.0001 — range of HbA1c reductions across agents; greater reduction with tirzepatide 15 mg q.w. than lixisenatide 20 μg q.d.
Further pooled results
Body weight change
- Weight reductions ranged from −0.75 ± 0.10 kg to −9.65 ± 0.56 kg
Safety
Gastrointestinal (GI) adverse event (AEs) (nausea, vomiting or diarrhoea)
- Despite high variability in efficacy, odds ratios (ORs) for GI AEs were similar across compounds/preparations
Original publication
Comparative efficacy and tolerability of currently approved incretin mimetics: A systematic analysis of placebo‐controlled clinical trials. Diabetes Obes Metab. Published 11 April 2025. doi:10.
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