Orforglipron Added to Titrated Insulin Glargine in Type 2 Diabetes: The ACHIEVE-5 Randomized Clinical Trial
Authors' conclusion
In participants with type 2 diabetes inadequately controlled by insulin glargine, addition of oral orforglipron significantly improved glycemic control and body weight, without increasing hypoglycemia risk, compared with placebo.
Study context
- Population
- Adults with T2D and inadequate glycemic control taking insulin glargine with or without metformin and/or SGLT2 inhibitors, 72 sites in the US, Brazil, China, Japan and Romania; median age 61.0 years, mean hemoglobin A1c (HbA1c) 8.50%507 completed
- Participants
- 546 adults
- Comparison
- Once-daily oral orforglipron 3 mg, 12 mg or 36 mg vs placebo, added to titrated insulin glargine
- 3 mgn = 137
- 12 mgn = 132
- 36 mgn = 136
- Placebon = 141reference
- Primary endpoint
- Mean HbA1c change from baseline (for the 12-mg and 36-mg dosages of orforglipron)
- Follow-up
- Week 40
Methodological detailsdouble-blind, phase 3, multicentre
- Double-blind
- Phase 3
- Multicentre
Primary result
As reported in the abstract
HbA1c change from baseline
12 mg
−1.88
mean · %
36 mg
−1.82
mean · %
Placebo
−0.79
mean · %
Each group vs placeboEstimated treatment difference, % (95% CI)P value
12 mg
−1.08(−1.33% to −0.83%)
P < 0.00136 mg
−1.03(−1.28% to −0.77%)
P < 0.001Secondary outcomes
| Outcome | 3 mg | 12 mg | 36 mg | Placebo | Estimated treatment difference (%) (95% CI) | P value | |
|---|---|---|---|---|---|---|---|
| HbA1c change from baseline, 3 mg (key secondary) · week 403 mgvs Placebo | mean −1.58 % | — not stated in the abstract | — not stated in the abstract | — not stated in the abstract | −0.78 (−1.02% to −0.55%) | P < 0.001 | |
| −1.5−1−0.500.5Difference, % (linear scale) |
— not stated in the abstract
Mean, %
| Outcome | 3 mg | 12 mg | 36 mg | Placebo |
|---|---|---|---|---|
| Percentage body weight change from baseline | −2.6 | −4.8 | −5.4 | 0.2 |
Key secondary outcomes (HbA1c targets <7.0% and ≤6.5%, body weight change) · week 40
- All key secondary outcomes demonstrated statistically significant differences in favor of orforglipron vs placebo
Safety
- Most frequent adverse events with orforglipron were gastrointestinal (mild to moderate)
- Orforglipron did not increase the risk of clinically significant hypoglycemia vs placebo
Original publication
Orforglipron Added to Titrated Insulin Glargine in Type 2 Diabetes: The ACHIEVE-5 Randomized Clinical Trial. JAMA. Published 4 August 2026. doi:10.
Composed by AI from the published abstract and checked against it. How Briefs are made →