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metformin + pioglitazone + sitagliptin + empagliflozin
- Development stage
- Phase 3
- Lead developer
- Azienda Ospedaliero‑Universitaria di Parma
- Modality
- Small Molecules
- Administration
- Oral
01
Overview
metformin + pioglitazone + sitagliptin + empagliflozin is a four-drug combination regimen evaluated for the induction of diabetes remission in patients with newly diagnosed type 2 diabetes. The regimen, known as POLYCHEM, combines four oral anti-diabetic agents with distinct, complementary mechanisms of action: metformin (an AMPK activator), pioglitazone (a PPAR-gamma agonist), sitagliptin (a DPP-4 inhibitor), and empagliflozin (an SGLT2 inhibitor). By simultaneously targeting multiple pathophysiological pathways of type 2 diabetes, the combination aims to achieve rapid glycemic control and promote beta-cell rest to induce drug-free remission. In the Phase III MIRACLE trial (NCT04271189) sponsored by the University Hospital of Parma, the regimen was compared against standard diabetes care but did not demonstrate superiority in achieving long-term diabetes remission.
- Other names
- POLYCHEMPOLYCHEM regimenempagliflozin + metformin + pioglitazone + sitagliptinmetformin + pioglitazone + sitagliptin + empagliflozin
02
Targets
AMPK (Adenosine monophosphate–activated protein kinase)V-ATPase (Vacuolar-type H+-ATPase)DPP-4 (Dipeptidyl Peptidase-IV)GIP (Glucose-dependent insulinotropic polypeptide)GLP-1 (Glucagon-like peptide-1)GSEC (Gamma-Secretase Complex)PPARG (Peroxisome proliferator-activated receptor gamma)SGLT2 (Sodium-glucose cotransporter protein subunit 2)
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