Combo Therapy May Improve HbA1c in Type 2 Diabetes

Oral orforglipron could be more effective in reducing hemoglobin A1c and body weight, with no increased risk of hypoglycemia in patients with inadequately controlled type 2 diabetes.

By
Andrea Surnit
June 12, 2026
4 min

Conexiant

Overview

The ACHIEVE-5 trial demonstrated that oral orforglipron significantly reduced HbA1c levels and body weight in patients with type 2 diabetes compared to placebo, without increasing the risk of hypoglycemia. The study involved 546 patients and showed that higher doses of orforglipron led to greater reductions in HbA1c and body weight.

Background

Type 2 diabetes mellitus (T2DM) remains a major public health issue, with many patients struggling to achieve adequate glycemic control. HbA1c is a critical marker for long-term glycemic exposure and is a primary target for diabetes management. New therapeutic options, such as incretin-based therapies, are being explored to enhance glycemic control and weight management in this population.

Data Highlights

Orforglipron Dose (mg)	Mean HbA1c Reduction (%)	Body Weight Change (%)
3	1.58	-3
12	1.88	-5
36	1.82	-5
Placebo	0.79	0

Key Findings

Orforglipron at doses of 3 mg, 12 mg, and 36 mg significantly reduced HbA1c levels compared to placebo.
57% of patients on 3 mg, 70% on 12 mg, and 65% on 36 mg achieved HbA1c levels below 7%.
Body weight decreased by approximately 3% with 3 mg and about 5% with both 12 mg and 36 mg doses of orforglipron.
Incidence of clinically significant hypoglycemia was comparable across all treatment groups.
The most common adverse events were gastrointestinal, primarily occurring during dose escalation.
No cases of pancreatitis or medullary thyroid cancer were reported during the study.

Clinical Implications

The findings suggest that orforglipron may be an effective addition to insulin therapy for improving glycemic control and managing body weight in patients with type 2 diabetes. Clinicians should consider the gastrointestinal side effects and treatment costs when discussing this option with patients.

Conclusion

Orforglipron, when added to titrated insulin glargine, significantly improved glycemic control and body weight without increasing hypoglycemia risk, indicating its potential role in diabetes management.