A novel non-PPARgamma insulin sensitizer: MLR-1023 clinicalproof-of-concept in type 2 diabetes mellitus

Moon Kyu Lee, Sin Gon Kim, Elaine Watkins, Min Kyong Moon, Sang Youl Rhee, Juan P. Frias, Choon Hee Chung, Seung Hwan Lee, Bradley Block, Bong Soo Cha, Hyeong Kyu Park, Byung Joon Kim, Frank Greenway

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    12 Citations (Scopus)


    Aim: MLR-1023, called Tolimidone when evaluated unsuccessfully by Pfizer for gastric ulcer disease, has been repurposed as a novel oral insulin sensitizer with its effects mediated by selective activation of Lyn kinase. We aimed to evaluate the optimal dose, efficacy and safety of MLR-1023 in patients with type 2 diabetes. Methods: Type 2 diabetes patients (18–75 years) on diet/exercise therapy were randomized and double-blinded to receive MLR-1023 (100-mg or 200-mg, once-daily [qd] or twice-daily [bid]) or matching placebo for 28 days. The primary endpoint was postprandial glucose (PPG) area under the curve (AUC0 3h) in a mixed meal tolerance test (MMTT) at day 29. Secondary endpoints included changes in fasting plasma glucose (FPG), insulin, HbA1c, lipids and body weight and adverse events. ANCOVA model was used for efficacy analysis. Results: The placebo-corrected least-squares mean differences (ΔLSM) in MMTT PPG AUC0-3 h (mmol/L) were −5.96 and −5.6 (both p = 0.03) in the MLR-1023 100-mg qd and 100-mg bid groups, respectively. The placebo-corrected ΔLSM in FPG (mmol/L) was −2.34 (p = 0.003) in the MLR-1023 100-mg qd group. Triglycerides improved with MLR-1023 (ΔLSM, −0.56 mmol/L, p = 0.07 and −0.59 mmol/L, p = 0.05) in the 200mgqd and 200 mg bid groups, respectively. Reductions in fasting insulin, HbA1c and body weight were not statistically significant. Most common adverse events with MLR-1023 treatment were headache (4.2%) and somnolence (2.5%). Conclusions: MLR-1023 100-mg once-daily for 4 weeks was the most effective dose with significant reduction in PPG AUC following a MMTT. MLR-1023 was safe and well-tolerated in patients with type 2 diabetes.

    Original languageEnglish
    Article number107555
    JournalJournal of Diabetes and its Complications
    Issue number5
    Publication statusPublished - 2020 May

    Bibliographical note

    Publisher Copyright:
    © 2020 Elsevier Inc.


    • Fasting glucose
    • Insulin sensitizer
    • Lyn kinase agonism
    • Mixed meal tolerance test
    • Tolimidone
    • Type 2 diabetes

    ASJC Scopus subject areas

    • Internal Medicine
    • Endocrinology, Diabetes and Metabolism
    • Endocrinology


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