Evaluating once-daily oral safiglipron against dapagliflozin in a multicenter trial, researchers reported that safiglipron successfully met primary non-inferiority endpoints for lowering blood sugar in adults with inadequately controlled type 2 diabetes over a 32-week treatment period.
The OUTSTAND-2 trial directly compared three distinct doses of oral safiglipron (30 mg, 60 mg, and 90 mg) against dapagliflozin (10 mg) in 810 randomized participants. All patients entered the study with type 2 diabetes inadequately controlled by stable metformin monotherapy. The investigation tracked primary changes in glycated hemoglobin (HbA1c) alongside comprehensive secondary metabolic and safety markers across a core 32-week period followed by a 20-week extension.
Safiglipron Lowers Blood Sugar as Effectively as Standard Medication
- What was tested: A new daily pill (safiglipron) to lower blood sugar was compared head-to-head against a standard diabetes medication (dapagliflozin) in 810 patients.
- Key finding: The experimental pill safely lowered blood sugar levels as effectively as, or better than, the standard comparator drug over 32 weeks of treatment.
Trial Design and Glycemic Efficacy Outperformed Dapagliflozin at Higher Doses
The OUTSTAND-2 trial enrolled adults aged 18 to 75 years with baseline HbA1c levels ranging between 7.5% and 11.0% and a body mass index of 19.0 to 40.0 kg m⁻². Following a 3-week single-blind run-in, participants were randomized to receive either oral safiglipron at 30 mg, 60 mg, or 90 mg daily, or dapagliflozin 10 mg daily. The trial maintained a double-blind, double-dummy active-comparator-controlled structure.
At week 32, the least-squares mean reductions in HbA1c under the primary non-inferiority estimand were −1.58% for safiglipron 30 mg, −1.50% for safiglipron 60 mg, and −1.68% for safiglipron 90 mg. In comparison, the dapagliflozin group achieved a reduction of −1.28%. Treatment differences versus dapagliflozin established non-inferiority across all three doses, as the upper confidence limits remained below the prespecified 0.4% margin. Superiority testing established statistical significance for the 90 mg dose with a one-sided P value of 0.0067, while the 60 mg dose did not reach formal superiority.
| Treatment Arm | Sample Size (N) | Baseline HbA1c (%) | HbA1c Change at Week 32 (%) |
|---|---|---|---|
| Safiglipron 30 mg | 202 | 8.60 | −1.58 |
| Safiglipron 60 mg | 203 | 8.60 | −1.50 |
| Safiglipron 90 mg | 203 | 8.60 | −1.68 |
| Dapagliflozin 10 mg | 202 | 8.60 | −1.28 |
Patient Retention and Safety Profiles Through Week 52
During the 52-week treatment period, treatment completion rates were documented at 88.1% for the safiglipron 30 mg group, 82.8% for the 60 mg group, 82.3% for the 90 mg group, and 93.1% for the dapagliflozin comparator arm. Safety endpoints tracked adverse events, hypoglycemic episodes, routine laboratory parameters, electrocardiograms, and diabetic retinopathy assessments across the 809 participants in the safety population.
Baseline demographic and clinical characteristics remained balanced across all arms. Participants presented with a mean age of 52.2 years, a mean body weight of 74.7 kg, and a median diabetes duration of 5.0 years. Exploratory subgroup evaluations indicated general consistency across most parameters, though a nominal interaction emerged regarding baseline HbA1c stratification above or below 8.5%.
Future Trajectory and Regulatory Considerations
The OUTSTAND-2 trial data position oral safiglipron as a therapeutic candidate for treating type 2 diabetes.
References
- OUTSTAND-2 Trial Investigators. Oral safiglipron versus dapagliflozin in type 2 diabetes: a randomized, double-blind, active-comparator-controlled trial.
Disclaimer: This article is for informational purposes only and does not substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions regarding a medical condition.
