With REMD's glucagon receptor antagonist, the study team propose to provide a comprehensive examination of the effect of elevated plasma glucagon concentrations in Type 2 Diabetes Mellitus (T2D) patients on: (i) glucose tolerance; (ii) insulin sensitivity in liver, muscle, and adipocytes; (iii) beta cell function; (iv) adipocyte inflammation.
Subjects with T2DM inadequately controlled on current medications will participate in a glucose tolerance test, euglycemic insulin clamp combined with 3-3H-glucose and 14-C glycerol infusion, adipose tissue biopsy, before and 12 weeks after treatment with REMD 477 or placebo.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
4
A biologic glucagon receptor agonist to which randomized subjects are assigned 2:1
Placebo for REMD-477 to which subjects will be randomized 1:2.
Texas Diabetes Institute
San Antonio, Texas, United States
Glycated Hemoglobin (HbA1c)
Change in HbA1c measured at baseline and after intervention administration
Time frame: Baseline to 13 weeks
Fasting Plasma glucose (FPG)
Change in fasting plasma glucose measured at baseline and after intervention administration
Time frame: Baseline to 13 weeks
Plasma glucose (PG)
Change in plasma PG measured at baseline and after intervention administration using an oral glucose tolerance test (OGTT)
Time frame: Baseline to 13 weeks
Hepatic insulin sensitivity
Change in hepatic glucose production (HGP)
Time frame: Baseline to 13 weeks
Whole body glucose disposal
Change in whole body glucose disposal measured in mg/kg/min
Time frame: Baseline to 13 weeks
Plasma Free Fatty Acids (FFA)
Change in plasma free fatty acids
Time frame: Baseline to 13 weeks
Muscle Insulin sensitivity
Change in muscle insulin sensitivity measured by insulin-stimulated glucose uptake during low dose high dose insulin clamp.
Time frame: Baseline to 13 weeks
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