CIR-0602K Demonstrates Synergistic Metabolic Benefit with Tirzepatide: New Data Presented at ObesityWeek 2025

GRAND RAPIDS, Mich., Nov. 4, 2025 /PRNewswire/ -- Cirius Therapeutics, Inc., a developer of innovative therapies for people suffering from diseases caused by insulin resistance and metabolic dysfunction, will be presenting new data today at ObesityWeek^® 2025 from preclinical obesity models on the complementary and synergistic effects of CIR-0602K (azemiglitazone potassium), an MPC inhibitor, in combination with tirzepatide, a dual GLP-1/GIP agonist.

The oral presentation by Jerry Colca, Ph.D, CSO of Cirius, will discuss how the combination therapy promotes better and more durable weight loss, and drives marked metabolic improvements in both muscle and adipose tissue versus single-agent tirzepatide.

Key findings from the data to be presented reveal that combining CIR-0602K and tirzepatide in mixed sex (male and female) diet-induced obese (DIO) mice:

• Enhances skeletal muscle metabolic function, strength, and mass.
  • Complemented tirzepatide in muscle by offsetting loss of muscle mass, strength, and mitochondria.
  • An increased expression of a broad set of genes that contribute to slow twitch, strength muscles and mitochondrial function further supported these results.
  • Aligns with DIO mouse data presented earlier this year showing that CIR-0602K mitigates the loss of lean muscle, strength and muscle mitochondria associated with GLP-1 agonist weight loss.
  • Also extends previous single-agent CIR-0602K clinical data demonstrating a marked increase in muscle metabolic function in persons with T2D and obesity.

• Remodels subcutaneous white adipose tissue (WAT) synergistically with tirzepatide.
  • Dramatically decreased WAT adipocyte size and increased cellular diversity.
  • Decreased inflammation and inflammatory cytokine production.
  • Increased adiponectin.
  • Increased WAT "beiging" (7-fold increase in UCP1 & 3.5-fold increase in PRDM16 expression) and other energetic futile cycles (SERCA, lipids) that increase energy expenditure.
  • As reported previously, CIR-0602K alone and in combination with tirzepatide reduces the visceral to subcutaneous adipose ratio, and these synergistic remodeling effects of the combination are also seen in the remaining visceral adipose tissue.

• Following discontinuation of tirzepatide, CIR-0602K reduces weight rebound, consistent with the beneficial metabolic effects seen in muscle and adipose.
  • Maintained 15% net weight loss in the mice that received the combination of Cir-0602K + tirzepatide and then continued on CIR-0602K, versus 1% weight gain in the tirzepatide only mice, a difference of 16 percentage points.
  • This represented roughly 50% of the weight loss through the end of tirzepatide treatment. More obese male mice (≥ 40g at baseline) in this combination group with continued CIR-0602K treatment maintained approximately 90% of their weight loss.
  • Even adding CIR-0602K after single-agent tirzepatide treatment significantly attenuated weight rebound.

• CIR-0602K alone and in combination tirzepatide triples expression of FGF-21 in WAT
  • Corroborates with results from Phase 2b EMMINENCE study on key MASLD/MASH endpoints.

"These findings underscore the potential of metabolic reprogramming with CIR-0602K to optimize incretin-based therapies by preserving muscle, restoring adipose tissue functionality, and promoting long-term metabolic health," said Dr. Colca. "We want to thank our collaborators on this work, including at the Dasman Diabetes Institute and St. Louis University. With them we are continuing to further our understanding of how the MPC inhibition and GLP-1 agonist pharmacologies work together."

"We have known for some time CIR-0602K decreases the ratio of visceral to subcutaneous fat, which is a key in fatty organ diseases and correlated with long term outcomes across metabolic diseases," said Robert Beardsley, Ph.D., CEO of Cirius. "We are now showing that it can also transform the metabolic role of both subcutaneous and visceral adipose – especially in combination with GLP-1 agonists. This is important not just in obesity/overweight and type 2 diabetes, but potentially also in MASLD/MASH and cardiovascular disease. The field is learning that adipose tissue health is an important factor inadequately addressed by current approaches that have focused only on skeletal muscle."

The oral presentation will take place on Tuesday, November 4, 2025 at the Georgia World Congress Center in Atlanta, GA.

Title: Azemiglitazone Potassium (0602K) Synergizes With Tirzepatide (TZP) to Remodel Muscle and Adipose
Date: November 4, 2025
Time: 2:15 PM ET
Location: Georgia World Congress Center, Room A411-A412

More detailed gene expression data will also be presented at an attended poster session, Cooperative Interactions Found in Combination of MPC Insulin Sensitizer and GLP1/GIP Agonist, from 2:30-3:30 PM ET on Wednesday, November 5 in Exhibit Hall A1.

About Cirius
Cirius is a clinical-stage pharmaceutical company focusing on mitochondrial pyruvate carrier (MPC), addressing the metabolic dysfunction that causes insulin resistance and the organ pathologies associated with type 2 diabetes (T2D) and obesity/overweight. Its lead product candidate, CIR-0602K, is a potential best-in-class novel small molecule being developed as a once-daily oral therapy designed to selectively inhibit the mitochondrial target MPC, which plays a central role in selecting mitochondrial energy substrates. MPC inhibition reprograms mitochondrial metabolism, reducing insulin resistance in cells and driving metabolic benefits in organs throughout the body. This markedly improves glycemic control in diabetes, body composition in obesity, liver function and fibrosis in metabolic dysfunction-associated steatohepatitis (MASH), and outcomes in cardiometabolic disorders.

About CIR-0602K
CIR-0602K has completed 7 US clinical trials including a 52-week placebo-controlled Phase 2b study in 392 participants with MASH with and without T2D, and a 28-day placebo-controlled Phase 2a study in 129 participants with T2D. In those clinical studies it markedly lowered HbA1c and insulin levels, and reduced liver injury and MASH – including on top of existing GLP-1 therapy. A pilot clinical study also showed CIR-0602K markedly reduces HbA1c, insulin levels and fat in muscle, and increases muscle metabolic function in people with obesity & T2D. A Phase 2a study in people with type 1 diabetes (T1D) and supported in part by Breakthrough T1D is expected to open 4Q25.

Preclinical studies also demonstrate increased lean muscle mass, strength and metabolic function, together with metabolically beneficial shifts in adipose tissue phenotype ("bad fat" to "good fat"), both alone and on top of GLP-1 and GLP-1/GIP agonists. In combination with GLP-1/GIP dual agonist tirzepatide, the synergistic transformation of subcutaneous adipose tissue includes dramatic reduction in adipocyte size and increase in "beiging." Selectively targeting MPC – while avoiding PPAR-γ activation – CIR-0602K harnesses the real-world proven efficacy of 1^st generation insulin sensitizers, such as pioglitazone, but without their side effect concerns.

Directly correcting a major underlying pathophysiology of chronic metabolic disease, CIR-0602K has the potential to become a cornerstone of therapy. Coupling this potent pharmacology with that of the GLP-1s could particularly benefit patients with T2D, obesity/overweight, MASH and other cardiometabolic diseases.

www.CiriusTx.com

Contact:
[email protected]

SOURCE Cirius Therapeutics