Initial Combination Therapy with Pioglitazone A total of 520 patients with type 2 diabetes and inadequate glycemic control on diet and exercise participated in a 24-week, randomized, double-blind study designed to assess the efficacy of JANUVIA as initial therapy in combination with pioglitazone
Lancet Diabetes Endocrinol 13:1528
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The breakdown process of BCAAs is similar in all species, initially forming branched-chain -keto acids (BCKAs) via branched-chain amino acid transferase (BCATs) and transferring nitrogen to nitrogen receptors (the most common nitrogen receptor is -ketoglutaric acid (-KG) to form glutamate)

Areas Without Adequate Human Evidence Long-term cardiovascular safety Long-term neurological safety Endocrine effects beyond selected hormone measurements Effects on glucose regulation in people Immune responses Allergic reactions Genotoxicity Carcinogenicity Effects in people with cancer or precancerous disease Reproductive and developmental toxicity Pregnancy safety Breastfeeding safety Paediatric exposure Medicine interactions Interaction with hormone or sleep treatments Repeated exposure over months or years Product-Quality Risks Incorrect amino-acid sequence Glu and Asp residue-order errors Wrong terminal groups Incorrect free-base or acetate designation Incorrect peptide quantity Deletion-sequence impurities Incomplete deprotection Residual synthesis reagents Residual solvents Peptide aggregates Degradation during transport or storage Unverified microbiological quality Unverified bacterial-endotoxin control Certificates unrelated to the supplied batch No reports does not mean no risk FDAs adverse-event database search found no Epitalon reports through December 2025

This SS linkage, together with the added N-terminal tyrosine, may support resistance to acidic gastric pH and proteolytic enzymes, thereby supporting oral bioavailability